CCNE1 and survival of patients with tubo-ovarian high-grade serous carcinoma: An Ovarian Tumor Tissue Analysis consortium study - Kang, Eun Young; Weir, Ashley; Meagher, Nicola S.; Farrington, Kyo; Nelson, Gregg S.; Ghatage, Prafull; Lee, Cheng Han; Riggan, Marjorie J.; Bolithon, Adelyn; Popovic, Gordana; Leung, Betty; Tang, Katrina; et al. (Cancer, 2023)
Background: Cyclin E1 (CCNE1) is a potential predictive marker and therapeutic target in tubo-ovarian high-grade serous carcinoma (HGSC). Smaller studies have revealed unfavorable associations for CCNE1 amplification and CCNE1 overexpression with survival, but to date no large-scale, histotype-specific validation has been performed. The hypothesis was that high-level amplification of CCNE1 and CCNE1 overexpression, as well as a combination of the two, are linked to shorter overall survival in HGSC. Methods: Within the Ovarian Tumor Tissue Analysis consortium, amplification status and protein level in 3029 HGSC cases and mRNA expression in 2419 samples were investigated. Results: High-level amplification (>8 copies by chromogenic in situ hybridization) was found in 8.6% of HGSC and overexpression (>60% with at least 5% demonstrating strong intensity by immunohistochemistry) was found in 22.4%. CCNE1 high-level amplification and overexpression both were linked to shorter overall survival in multivariate survival analysis adjusted for age and stage, with hazard stratification by study (hazard ratio [HR], 1.26; 95% CI, 1.08-1.47, p =.034, and HR, 1.18; 95% CI, 1.05-1.32, p =.015, respectively). This was also true for cases with combined high-level amplification/overexpression (HR, 1.26; 95% CI, 1.09-1.47, p =.033). CCNE1 mRNA expression was not associated with overall survival (HR, 1.00 per 1-SD increase; 95% CI, 0.94-1.06; p =.58). CCNE1 high-level amplification is mutually exclusive with the presence of germline BRCA1/2 pathogenic variants and shows an inverse association to RB1 loss. Conclusion: This study provides large-scale validation that CCNE1 high-level amplification is associated with shorter survival, supporting its utility as a prognostic biomarker in HGSC.
CRIS-Team Scopus Importer:2023-02-17
Keywords: CCNE1 amplification; cyclin E1 expression; high-grade serous carcinoma; ovarian cancer; prognosis

CDK4/6 Inhibition – Therapy Sequences and the Quest to Find the Best Biomarkers – an Overview of Current Programs - Schneeweiss, Andreas; Brucker, Sara Y.; Hübner, Hanna; Volmer, Lea L.; Hack, Carolin; Seitz, Katharina; Rübner, Matthias; Heublein, Sabine; Thewes, Verena; Lüftner, Diana; Lux, Michael P.; Jurhasz-Böss, Ingolf; et al. (Geburtshilfe und Frauenheilkunde, 2024)
In recent years, new targeted therapies have been developed to treat patients with hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) breast cancer. Some of these therapies have not just become the new therapy standard but also led to significantly longer overall survival rates. The cyclin-dependent kinase 4 and 6 inhibitors (CDK4/6i) have become the therapeutic standard for first-line therapy. Around 70 - 80% of patients are treated with a CDK4/6i. In recent years, a number of biomarkers associated with progression, clonal selection or evolution have been reported for CDK4/6i and their endocrine combination partners. Understanding the mechanisms behind treatment efficacy and resistance is important. A better understanding could contribute to planning the most effective therapeutic sequences and utilizing basic molecular information to overcome endocrine resistance. One study with large numbers of patients which aims to elucidate these mechanisms is the Comprehensive Analysis of sPatial, TempORal and molecular patterns of ribociclib efficacy and resistance in advanced Breast Cancer patients (CAPTOR BC) trial. This overview summarizes the latest clinical research on resistance to endocrine therapies, focusing on CDK4/6 inhibitors and discussing current study concepts.
CRIS-Team Scopus Importer:2024-06-14
Keywords: breast cancer; CDK4/6; therapy

CDK4/6 Inhibitors—Overcoming Endocrine Resistance Is the Standard in Patients with Hormone Receptor-Positive Breast Cancer - Nabieva, Naiba; Fasching, Peter (Cancers, 2023)
Purpose of review: Tamoxifen and aromatase inhibitors can be considered as some of the first targeted therapies. For the past 30 years, they were the endocrine treatment standard in the advanced and early breast cancer setting. CDK4/6 inhibitors, however, are the first substances in almost two decades to broadly improve the therapeutic landscape of hormone receptor-positive breast cancer patients for the upcoming years. This review is designed to discuss the recent history, current role, future directions and opportunities of this substance class. Recent findings: The CDK4/6 inhibitors abemaciclib, dalpiciclib, palbociclib and ribociclib have all demonstrated a statistically significant improvement in progression-free survival in advanced disease. However, to date, abemaciclib and ribociclib are the only CDK4/6 inhibitors to have shown an improvement in overall survival in patients with metastatic breast cancer. Moreover, abemaciclib is the first CDK4/6 inhibitor to also reduce the risk of recurrence in those with early-stage disease. Further CDK inhibitors, treatment combinations with other drugs and different therapy sequences are in development. Summary: Achieving significant improvements in survival rates in the advanced and early breast cancer treatment setting, CDK4/6 inhibitors have set a new standard of care for patients with advanced breast cancer. It remains important to better understand resistance mechanisms to be able to develop novel substances and treatment sequences.
CRIS-Team Scopus Importer:2023-04-14
Keywords: abemaciclib; breast cancer; CDK4/6 inhibitor; dalpiciclib; endocrine treatment; palbociclib; ribociclib

Cell-based endometrial regeneration: current status and future perspectives - Keyhanvar, Neda; Zarghami, Nosratollah; Bleisinger, Nathalie; Hajipour, Hamed; Fattahi, Amir; Nouri, Mohammad; Dittrich, Ralf (Cell and Tissue Research, 2021)
Endometrial-related disorders including Asherman's syndrome, thin endometrium, pelvic organ prolapse, and cesarean scar pregnancies can be accompanied by different symptoms such as amenorrhea, infertility, abnormal placental implantation and recurrent miscarriage. Different methods have been introduced to overcome these problems such as surgery and hormonal therapy but none of them has shown promising outcomes. On the other hand, the development of novel regenerative therapeutic strategies has opened new avenues for the treatment of endometrial-related deficiencies. In this regard, different types of scaffolds, acellular matrices and also cell therapy with adult or stem cells have been investigated for the treatment of endometrial-related deficiencies. In this paper, we review the current status of cell-based endometrium regeneration using scaffold dependent and scaffold-free methods and future perspectives in this field. Moreover, we discuss the endometrial diseases that can be candidates for cell-based treatments. Also, the cells with the potential for endometrial regeneration are explained.
CRIS-Team WoS Importer:2021-03-19

Cell-In-Cell Structures in Early Breast Cancer Are Prognostically Valuable - Bauer, Mareike; Hildebrand, Laura; Rosahl, Marie-Charlotte; Erber, Ramona; Schnellhardt, Sören; Büttner-Herold, Maike; Putz, Florian; Ott, Oliver; Hack, Carolin; Fietkau, Rainer; Distel, Luitpold (Cells, 2023)
Cell-in-cell (CIC) structures in breast cancer have so far been studied in a small inhomogeneous patient population, suggesting the prognostic importance of CIC. In the present study, we focused on CIC in early hormone-sensitive breast cancer. With in vitro co-culture experiments, we compared the homotypic phagocytic capacity of two breast cancer cell lines to that of primary human fibroblasts. Afterward, we studied 601 tissue specimens from 147 patients participating in an institutional accelerated partial breast irradiation (APBI) phase II trial. Both breast cancer cell lines performed non-professional phagocytosis at a higher rate than primary human fibroblasts. In this study cohort, 93.2% of the patients had T1 tumours, and 6.8% had T2 tumours. CIC was found in 61.2% of the patients, with a CIC rate ranging from <1/mm2 to 556.5/mm2 with a mean of 30.9/mm2 ± 68.4/mm2. CIC structures were prognostically favourable for local recurrence-free survival and disease-free survival. Regarding metastasis-free survival, CIC-positive patients had an unfavourable prognosis. Subgroup analysis indicated a correlation between a high proliferation index and high CIC rates. CIC had the highest prognostic value in young breast cancer patients (p = 0.004). With this study, we provide further evidence of CIC as a prognostic marker in breast cancer.
CRIS-Team Scopus Importer:2023-01-20
Keywords: accelerated partial breast irradiation; breast cancer; cell-in-cell; ionizing radiation; non-professional phagocytosis; radiotherapy

Cerebroplacental versus Umbilicocerebral Ratio—Analyzing the Predictive Value Regarding Adverse Perinatal Outcomes in Low- and High-Risk Fetuses at Term - Stumpfe, Florian; Mayr, Andreas; Schneider, Michael; Kehl, Sven; Stübs, Frederik; Antoniadis, Sophia; Titzmann, Adriana; Pontones, Constanza; Bayer, Christian M.; Beckmann, Matthias; Faschingbauer, Florian (Medicina, 2023)
Background and Objectives: The aim of this study was to investigate the prediction of adverse perinatal outcomes using the cerebroplacental (CPR) and umbilicocerebral (UCR) ratios in different cohorts of singleton pregnancies. Materials and Methods: In this retrospective cohort study, we established our own Multiple of Median (MoM) for CPR and UCR. The predictive value for both ratios was studied in the following outcome parameters: emergency cesarean delivery, operative intervention (OI), OI due to fetal distress, 5-min Apgar < 7, admission to neonatal intensive care unit, and composite adverse perinatal outcome. The performance of the ratios was assessed in the following cohorts: total cohort (delivery ≥ 37 + 0 weeks gestation, all birth weight centiles), low-risk cohort (delivery ≥ 37 + 0 weeks gestation, birth weight ≥ 10. centile), prolonged pregnancy cohort (delivery ≥ 41 + 0 weeks gestation, birth weight ≥ 10. centile) and small-for-gestational-age fetuses (delivery ≥ 37 + 0 weeks gestation, birth weight < 10. centile). The underlying reference values for MoM were estimated using quantile regression depending on gestational age. Prediction performance was evaluated using logistic regression models assessing the corresponding Brier score, combining discriminatory power and calibration. Results: Overall, 3326 cases were included. Across all cohorts, in the case of a significant association between a studied outcome parameter and CPR, there was an association with UCR, respectively. The Brier score showed only minimal differences for both ratios. Conclusions: Our study provides further evidence regarding predictive values of CPR and UCR. The results of our study suggest that reversal of CPR to UCR does not improve the prediction of adverse perinatal outcomes.
CRIS-Team Scopus Importer:2023-09-08
Keywords: cerebroplacental ratio; CPR; UCR; umbilicocerebral ratio

Cervical cancer Zervixkarzinom - Beckmann, Matthias; Schmidberger, H. (Onkologe, 2020)
CRIS-Team Scopus Importer:2020-06-30

Cervical intraepithelial neoplasia grade 2/3: development during pregnancy and postpartum - Stübs, Frederik; Mergel, F.; Koch, M. C.; Dietl, Anna; Schulmeyer, Carla; Adler, Werner; Geppert, Carol-Immanuel; Hartmann, Arndt; Knöll, Antje; Beckmann, Matthias; Gaß, Paul; Mehlhorn, G. (GEBURTSHILFE UND FRAUENHEILKUNDE, 2022)
CRIS-Team WoS Importer:2022-11-04

Cervical intraepithelial neoplasia grade 3: development during pregnancy and postpartum - Stübs, Frederik; Mergel, Franziska; Koch, Martin; Dietl, Anna; Schulmeyer, Carla; Adler, Werner; Geppert, Carol-Immanuel; Hartmann, Arndt; Knöll, Antje; Beckmann, Matthias; Gaß, Paul; Mehlhorn, Grit (Archives of Gynecology and Obstetrics, 2022)
Purpose: The aims of the present study were to evaluate the development of untreated cervical intraepithelial neoplasia (CIN) 3 during pregnancy and to assess persistence, progression, and regression rates postpartum to identify factors associated with regression. Methods: In a tertiary gynecology and obstetrics department, a total of 154 pregnant women with CIN 3 were treated in the dysplasia unit. The follow-up findings were analyzed retrospectively on the basis of histological, cytological, and human papillomavirus (HPV) testing of 154 pregnant women confirmed as having CIN 3 in colposcopically guided biopsies. Results: The rates of persistence, regression, and progression of CIN 3 in these women were 76.1%, 20% and 3.2%, respectively. Data for the delivery mode was available for 126 women. The rate of regression was almost twice as high with vaginal delivery as with cesarean section, at 27.4 vs. 15.2%, whereas the rate of progression was lower with vaginal delivery, at 2.7 vs. 6.5%. Conclusion: The rate of persistence of CIN observed in this study is comparable to that reported in other studies. The study provides strong evidence for greater regression among women who have vaginal deliveries. Careful work-up is recommended postpartum for this group of women in order to rule out persistent CIN 3 or invasive disease.
CRIS-Team Scopus Importer:2022-11-04
Keywords: Cervical dysplasia; High-grade squamous intraepithelial lesion (HSIL); Mode of delivery; Pregnancy; Treatment

Challenges and Opportunities for Real-World Evidence in Metastatic Luminal Breast Cancer - Lüftner, Diana; Hartkopf, Andreas D.; Lux, Michael P.; Overkamp, Friedrich; Tesch, Hans; Titzmann, Adriana; Pöschke, Patrik; Wallwiener, Markus; Müller, Volkmar; Beckmann, Matthias; Belleville, Erik; Janni, Wolfgang; et al. (Breast Care, 2021)
Background: The therapeutic armamentarium for patients with metastatic breast cancer is becoming more and more specific. Recommendations from clinical trials are not available for all treatment situations and patient subgroups, and it is therefore important to collect real-world data. Summary: To develop recommendations for up-to-date treatments and participation in clinical trials for patients with metastatic breast cancer, the Prospective Academic Translational Research PRAEGNANT Network was established to optimize the quality of oncological care in the advanced therapeutic setting. The main aim of PRAEGNANT is to systematically record medical care for patients with metastatic breast cancer in the real-life setting, including the outcome and side effects of different treatment strategies, to monitor quality-of-life changes during therapy, to identify patients eligible for participation in clinical studies, and to allow targeted therapies based on the molecular structures of breast carcinomas. Key Messages: This article describes the PRAEGNANT network and sheds light on the question of whether the various end points from clinical trials can be transferred to the real-world treatment situation.
CRIS-Team Scopus Importer:2021-04-02
Keywords: Breast cancer; Luminal; Metastasis; PRAEGNANT; Real-world evidence

Changes in serum levels of miR-21, miR-210, and miR-373 in HER2-positive breast cancer patients undergoing neoadjuvant therapy: a translational research project within the Geparquinto trial - Mueller, Volkmar; Gade, Stephan; Steinbach, Bettina; Loibl, Sibylle; Von Minckwitz, Gunter; Untch, Michael; Schwedler, Kathrin; Luebbe, Kristina; Schem, Christian; Fasching, Peter; Mau, Christine; Pantel, Klaus; et al. (Breast Cancer Research and Treatment, 2014)
Trastuzumab and lapatinib are established treatments for patients with HER2 (human epidermal growth factor receptor 2)-positive breast cancer with different mechanisms of action. The focus of this study is to investigate, whether altered expression levels of potentially relevant microRNAs (miRs) in serum are associated with response to trastuzumab or lapatinib. Circulating miR-21, miR-210, and miR-373 were quantified with TaqMan MicroRNA assays in serum of 127 HER2-postive breast cancer patients before and after neoadjuvant therapy and in 19 healthy controls. Patients received chemotherapy combined with either trastuzumab or lapatinib within the prospectively randomized Geparquinto trial. The association between miR levels and pathological response (pCR) to therapy and type of therapy was examined. Serum levels of miR-21 (p = 5.04e-08, p = 1.43e-10), miR-210 (p = 0.00151, p = 1.6e-05), and miR-373 (p = 7.87e-06, p = 1.75e-07) were significantly higher in patients before and after chemotherapy than in healthy women. Concentrations of miR-21 (p = 5.73e-08), miR-210 (p = 0.000724), and miR-373 (p = 0.00209) increased further after chemotherapy. A significant association of higher serum levels of miR-373 with advanced clinical tumor stage could be detected (p < 0.002). An association of miR-21 levels before (p = 0.0091) and after (p = 0.037) chemotherapy with overall survival of the patients could be detected, independent of type of anti-HER2 therapy. No association of circulating miRs with pCR was found. Our findings demonstrate a specific influence of neoadjuvant therapy on the serum levels of miR-21, miR-210, and miR-373 in breast cancer patients together with a prognostic value of miR-21.
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Characteristics and clinical outcome of breast cancer patients with asymptomatic brain metastases - Laakmann, E.; Witzel, I.; Neunhoeffer, T.; Weide, R.; Schmidt, M.; Park-Simon, T. W.; Mobus, V.; Mundhenke, Christoph; Polasik, A.; Lubbe, K.; Hesse, T.; Riecke, K.; et al. (EUROPEAN JOURNAL OF CANCER, 2020)
CRIS-Team WoS Importer:2020-11-13

Characteristics and clinical outcome of breast cancer patients with asymptomatic brain metastases - Laakmann, Elena; Witzel, Isabell; Neunhöffer, Tanja; Weide, Rudolf; Schmidt, Marcus; Park-Simon, Tjoung Won; Möbus, Volker; Mundhenke, Christoph; Polasik, Arkadius; Lübbe, Kristina; Hesse, Tobias; Riecke, Kerstin; et al. (Cancers, 2020)
Background: Brain metastases (BM) have become a major challenge in patients with metastatic breast cancer. Methods: The aim of this analysis was to characterize patients with asymptomatic BM (n = 580) in the overall cohort of 2589 patients with BM from our Brain Metastases in Breast Cancer Network Germany (BMBC) registry. Results: Compared to symptomatic patients, asymptomatic patients were slightly younger at diagnosis (median age: 55.5 vs. 57.0 years, p = 0.01), had a better performance status at diagnosis (Karnofsky index 80–100%: 68.4% vs. 57%, p < 0.001), a lower number of BM (>1 BM: 56% vs. 70%, p = 0.027), and a slightly smaller diameter of BM (median: 1.5 vs. 2.2 cm, p < 0.001). Asymptomatic patients were more likely to have extracranial metastases (86.7% vs. 81.5%, p = 0.003) but were less likely to have leptomeningeal metastasis (6.3% vs. 10.9%, p < 0.001). Asymptomatic patients underwent less intensive BM therapy but had a longer median overall survival (statistically significant for a cohort of HER2-positive patients) compared to symptomatic patients (10.4 vs. 6.9 months, p < 0.001). Conclusions: These analyses show a trend that asymptomatic patients have less severe metastatic brain disease and despite less intensive local BM therapy still have a better outcome (statistically significant for a cohort of HER2-positive patients) than patients who present with symptomatic BM, although a lead time bias of the earlier diagnosis cannot be ruled out. Our analysis is of clinical relevance in the context of potential trials examining the benefit of early detection and treatment of BM.
CRIS-Team Scopus Importer:2020-10-09
Keywords: Asymptomatic; Brain metastases; Breast cancer

Characterization of Hormone Receptor and HER2 Status in Breast Cancer Using Mass Spectrometry Imaging - Gonçalves, Juliana Pereira Lopes; Bollwein, Christine; Noske, Aurelia; Jacob, Anne; Jank, Paul; Loibl, Sibylle; Nekljudova, Valentina; Fasching, Peter; Karn, Thomas; Marmé, Frederik; Müller, Volkmar; Schem, Christian; et al. (International Journal of Molecular Sciences, 2023)
Immunohistochemical evaluation of estrogen receptor, progesterone receptor, and human epidermal growth factor receptor-2 status stratify the different subtypes of breast cancer and define the treatment course. Triple-negative breast cancer (TNBC), which does not register receptor overexpression, is often associated with worse patient prognosis. Mass spectrometry imaging transcribes the molecular content of tissue specimens without requiring additional tags or preliminary analysis of the samples, being therefore an excellent methodology for an unbiased determination of tissue constituents, in particular tumor markers. In this study, the proteomic content of 1191 human breast cancer samples was characterized by mass spectrometry imaging and the epithelial regions were employed to train and test machine-learning models to characterize the individual receptor status and to classify TNBC. The classification models presented yielded high accuracies for estrogen and progesterone receptors and over 95% accuracy for classification of TNBC. Analysis of the molecular features revealed that vimentin overexpression is associated with TNBC, supported by immunohistochemistry validation, revealing a new potential target for diagnosis and treatment.
CRIS-Team Scopus Importer:2023-02-24
Keywords: breast cancer; histopathology; mass spectrometry imaging; proteomics; tissue typing

Characterization of Molecular Subtypes of Paget Disease of the Breast Using Immunohistochemistry and In Situ Hybridization - Wachter, David; wachter, peter wolf; Fasching, Peter; Beckmann, Matthias; Hack, Carolin; Riener, Marc-Oliver; Hartmann, Arndt; Strehl, Johanna D. (Archives of Pathology & Laboratory Medicine, 2018)
CONTEXT: - Paget disease of the breast, in most cases, represents intraepidermal spread of ductal carcinoma in situ. Molecular subtypes of invasive carcinoma of the breast have prognostic and therapeutic significance and show characteristic distribution. Little is known about the distribution of molecular subtypes in Paget disease of the breast. OBJECTIVES: - To examine the distribution of molecular subtypes in Paget disease of the breast and to compare them to concurrent invasive carcinoma of the breast, if present. DESIGN: - We examined 48 cases of Paget disease of the breast with immunohistochemistry and antibodies against estrogen and progesterone receptors, human epidermal growth factor receptor 2 (HER2), and Ki-67, as well as HER2 chromogenic in situ hybridization, to classify the cases into molecular subtypes. Then, we compared the results to the molecular subtypes of associated, invasive carcinoma of the breast, if present. RESULTS: - The HER2 subtype was the most common found in Paget disease of the breast, followed by the luminal B subtype and 2 cases of the triple-negative subtype. The associated, invasive carcinoma cases were most often of the luminal B subtype, followed by the HER2 subtype and the triple-negative subtype. The molecular subtype of Paget disease and invasive carcinoma was congruent in most of the cases. CONCLUSIONS: - Molecular subtypes of invasive carcinoma of the breast can already be detected in Paget disease. The distribution of molecular subtypes of Paget disease and of Paget disease-associated, invasive carcinoma differs from invasive carcinoma without associated Paget disease, with the HER2 subtype overrepresented in Paget disease and associated, invasive carcinoma and the luminal and triple-negative subtypes underrepresented.
EVALuna2:34808

Characterization of the impact of immune checkpoint inhibitors on platelet activation and aggregation - Schlüter, Julian; Cunningham, Sarah; Zimmermann, Robert; Achenbach, Susanne; Kramer, Rafaela; Erdmann, Michael; Beckmann, Matthias; Heinzerling, Lucie; Hackstein, Holger (Immunobiology, 2023)
Immune checkpoint inhibitors (ICIs) are effective oncological drugs which block cellular check-point receptors typically targeted by tumor immune evasion strategies. Despite their benefits, clinicians have reported treatment-associated thromboembolism during ICI therapy in recent years. Though several theories on this ICI-associated pathogenesis exist, the direct effects of ICIs on platelets remains unknown. We therefore investigated the potential direct and indirect effect of PD-1, PD-L1 and CTLA-4-targeting ICIs on platelet functionality in multifaceted in vitro experiments. Interestingly, we could not observe a clear effect of ICI on platelet aggregation and primary hemostasis in whole blood and platelet concentrate-based assays. Furthermore, the presence of ICIs in toll-like receptor stimulation had no significant impact on platelet surface marker expression. In a second approach, we investigated the indirect immunological impact of ICIs on platelet activation by exposing platelets to supernatants from ICI- and Staphylococcal enterotoxin B-exposed PBMCs. Whereas ICIs affected IL-2 levels in supernatants, we could not detect clear differences in the secretion of pro-thrombogenic factors and platelet responses. The obtained data suggest that the direct influence of ICIs on platelet activation or the influence of altered T cell function on platelet activation cannot be considered a major factor in the development of thrombotic events.
CRIS-Team Scopus Importer:2023-01-13
Keywords: Immune checkpoint inhibitors; Platelet activation; Platelet function tests; Platelets; Thrombosis

Characterizing mammographic images by using generic texture features - Häberle, Lothar; Wagner, Florian; Fasching, Peter; Jud, Sebastian; Heusinger, Katharina; Löhberg, Christian; Hein, Alexander; Bayer, Christian M.; Hack, Carolin; Lux, Michael P.; Binder, Katja; Elter, Matthias; et al. (Breast Cancer Research, 2012)
Introduction: Although mammographic density is an established risk factor for breast cancer, its use is limited in clinical practice because of a lack of automated and standardized measurement methods. The aims of this study were to evaluate a variety of automated texture features in mammograms as risk factors for breast cancer and to compare them with the percentage mammographic density (PMD) by using a case-control study design.Methods: A case-control study including 864 cases and 418 controls was analyzed automatically. Four hundred seventy features were explored as possible risk factors for breast cancer. These included statistical features, moment-based features, spectral-energy features, and form-based features. An elaborate variable selection process using logistic regression analyses was performed to identify those features that were associated with case-control status. In addition, PMD was assessed and included in the regression model.Results: Of the 470 image-analysis features explored, 46 remained in the final logistic regression model. An area under the curve of 0.79, with an odds ratio per standard deviation change of 2.88 (95% CI, 2.28 to 3.65), was obtained with validation data. Adding the PMD did not improve the final model.Conclusions: Using texture features to predict the risk of breast cancer appears feasible. PMD did not show any additional value in this study. With regard to the features assessed, most of the analysis tools appeared to reflect mammographic density, although some features did not correlate with PMD. It remains to be investigated in larger case-control studies whether these features can contribute to increased prediction accuracy. © 2012 Fasching et al.; licensee BioMed Central Ltd.
CRIS-Team Scopus Importer:2021-07-19

Chemotherapy (CT)-induced anaemia in patients (pts) treated with dose-dense regimen: Results of the prospectively randomised anaemia substudy from the neoadjuvant GeparOcto study - Tesch, H.; Loibl, S.; Kast, K.; Jackisch, C.; Moebus, V.; Buchen, S.; Untch, M.; Hanusch, C.; Seiler, S.; Weigel, M.; Fasching, Peter; Rhiem, K.; et al. (ANNALS OF ONCOLOGY, 2019)
CRIS-Team WoS Importer:2019-11-08

Chemotherapy-induced ovarian failure in young women with early breast cancer: Prospective analysis of four randomised neoadjuvant/adjuvant breast cancer trials - Furlanetto, Jenny; Marmé, Frederik; Seiler, Sabine; Thode, Christian; Untch, Michael; Schmatloch, Sabine; Schneeweiss, Andreas; Bassy, Martina; Fasching, Peter; Strik, Dominika; Stickeler, Elmar; Schem, Christian; et al. (European Journal of Cancer, 2021)
Background: Young women receiving chemotherapy for early breast cancer (EBC) have a high probability for ovarian failure, defined by chemotherapy-induced amenorrhea (CIA) as a surrogate. CIA is insufficiently reliable and reproducible. We analysed chemotherapy-induced ovarian failure (CIOF) by assessing hormone parameters, CIA, and antral follicle count (AFC). Methods: Blood samples of women aged ≤45 years treated with anthracycline/taxane-based chemotherapy for EBC from four neoadjuvant/adjuvant trials were collected at baseline, at the end of treatment (EOT), and at 6, 12, 18, and 24 months after EOT. Centrally assessed oestradiol (cutoff <52.2 ng/L) and follicle-stimulating hormone (cutoff >12.4IU/L) were used to define CIOF for patients with baseline premenopausal hormone levels, anti-Müllerian hormone (AMH), and AFC to assess ovarian reserve. Further analyses included CIA, regain of premenopausal hormone levels, and disease-free survival (DFS) also in subgroups. Results: Six hundred ninety-six patients aged ≤45 years had premenopausal hormone levels at baseline. Overall, 85.1% (592/696) experienced CIOF at EOT, and 147 of 592 had further hormone measurements after EOT. Of those, 32.7% (48/147) regained premenopausal hormone levels after 6 months, 57.9% (66/114) regained premenopausal hormone levels after 12 months, 83.0% (73/88) regained premenopausal hormone levels after 18 months, and 89.2% (74/83) regained premenopausal hormone levels after 24 months. After 24 months, 72.4% (21/29) of patients without CIOF and 100% (14/14) with CIOF had low AMH levels. Four-year DFS without CIOF versus CIOF was 65.9% versus 84.6% (hazard ratio [HR] = 2.09, 95% confidence interval [CI]: 1.37–3.19; P < 0.001); in hormone receptor positive 61.8% versus 87.5% (HR = 2.69, 95% CI: 1.57–4.60; P < 0.001); in <30 years 68.3% versus 92.6% (HR = 4.87, 95% CI: 1.05–22.63; P = 0.026). Conclusion: Most premenopausal women experienced CIOF after chemotherapy for EBC. After 2 years, nearly all regain premenopausal hormone levels. CIOF was associated with better DFS, especially in patients with hormone receptor–positive EBC or aged <30 years.
CRIS-Team Scopus Importer:2021-06-18
Keywords: Chemotherapy-induced amenorrhea; Chemotherapy-induced ovarian failure; Early breast cancer; Ovarian reserve; Young women

Chylous ascites after lymphadenectomy for gynecological malignancies - Thiel, Falk C.; Parvanta, Parnian; Hein, Alexander; Mehlhorn, Grit; Lux, Michael P.; Renner, Stefan; Preisner, Achim; Beckmann, Matthias; Schrauder, Michael G. (Journal of Surgical Oncology, 2016)
BACKGROUND AND OBJECTIVES: Chylous ascites, an accumulation of milky-white lymph fluid in the peritoneal cavity, is a rare complication following retroperitoneal lymphadenectomy. This study evaluated the appearance and management of chylous ascites following lymphadenectomy for gynecological malignancies. METHODS: A total of 931 patients who underwent lymphadenectomy for gynecological malignancies at Erlangen University Hospital between 2002 and 2013 were reviewed retrospectively. RESULTS: Chylous ascites occurred postoperatively in 28 of the 931 patients (3.0%). All patients with chylous ascites had undergone combined systematic para-aortic and pelvic lymphadenectomy (SAPL). Patients with chylous ascites had a larger mean number of lymph nodes removed (51.9 vs. 40.0, P = 0.002) and the proportion of laparoscopic SAPLs was significantly higher (20/28; 71.4%) in comparison with open surgery (8/28; 28.6%) (P < 0.0001). Additional parameters, such as the number of positive lymph nodes, were not significantly associated with the occurrence of chylous ascites. Conservative management was sufficient to resolve chylous ascites in all observed cases, with a mean time to resolution of 8 days. CONCLUSIONS: Postoperative chylous ascites was more frequently observed in patients with laparoscopic SAPL in comparison with open SAPL and was strongly associated with a larger mean number of removed lymph nodes. J. Surg. Oncol. 2016;114:613-618. © 2016 Wiley Periodicals, Inc.
EVALuna2:32952

Circulating micro-RNAs as potential blood-based markers for early stage breast cancer detection - Schrauder, Michael G.; Strick, Reiner; Schulz-Wendtland, Rüdiger; Strissel, Pamela; Kahmann, Laura; Loehberg, Christian R.; Lux, Michael P.; Jud, Sebastian; Hartmann, Arndt; Hein, Alexander; Bayer, Christian M.; Bani, Mayada; et al. (PLoS ONE, 2012)
Introduction: MicroRNAs (miRNAs, miRs) are a class of small, non-coding RNA molecules with relevance as regulators of gene expression thereby affecting crucial processes in cancer development. MiRNAs offer great potential as biomarkers for cancer detection due to their remarkable stability in blood and their characteristic expression in many different diseases. We investigated whether microarray-based miRNA profiling on whole blood could discriminate between early stage breast cancer patients and healthy controls. Methods: We performed microarray-based miRNA profiling on whole blood of 48 early stage breast cancer patients at diagnosis along with 57 healthy individuals as controls. This was followed by a real-time semi-quantitative Polymerase Chain Reaction (RT-qPCR) validation in a separate cohort of 24 early stage breast cancer patients from a breast cancer screening unit and 24 age matched controls using two differentially expressed miRNAs (miR-202, miR-718). Results: Using the significance level of p<0.05, we found that 59 miRNAs were differentially expressed in whole blood of early stage breast cancer patients compared to healthy controls. 13 significantly up-regulated miRNAs and 46 significantly down-regulated miRNAs in our microarray panel of 1100 miRNAs and miRNA star sequences could be detected. A set of 240 miRNAs that was evaluated by radial basis function kernel support vector machines and 10-fold cross validation yielded a specificity of 78.8%, and a sensitivity of 92.5%, as well as an accuracy of 85.6%. Two miRNAs were validated by RT-qPCR in an independent cohort. The relative fold changes of the RT-qPCR validation were in line with the microarray data for both miRNAs, and statistically significant differences in miRNA-expression were found for miR-202. Conclusions: MiRNA profiling in whole blood has potential as a novel method for early stage breast cancer detection, but there are still challenges that need to be addressed to establish these new biomarkers in clinical use. © 2012 Schrauder et al.
CRIS-Team Scopus Importer:2021-07-19

Circulating miR-148b and miR-133a as biomarkers for breast cancer detection - Shen, Jie; Hu, Qiang; Schrauder, Michael; Yan, Li; Wang, Dan; Medico, Leonardo; Guo, Yuqing; Yao, Song; Zhu, Qianqian; Liu, Biao; Qin, Maochun; Beckmann, Matthias; et al. (Oncotarget, 2014)
Circulating microRNAs have drawn a great deal of attention as promising novel biomarkers for breast cancer. However, to date, the results are mixed. Here, we performed a three-stage microRNA analysis using plasma samples from breast cancer patients and healthy controls, with efforts taken to address several pitfalls in detection techniques and study design observed in previous studies. In the discovery phase with 122 Caucasian study subjects, we identified 43 microRNAs differentially expressed between breast cancer cases and healthy controls. When those microRNAs were compared with published data from other studies, we identified three microRNAs, including miR-148b, miR-133a and miR-409-3p, whose plasma levels were significantly higher in breast cancer cases than healthy controls and were also significant in previous independent studies. In the validation phase with 50 breast cancer cases and 50 healthy controls, we validated the associations with breast cancer detection for miR-148b and miR-133a (P = 1.5×10-6 and 1.3×10-10, respectively). In the in-vitro study phase, we found that both miR-148b and miR-133a were secreted from breast cancer cell lines, showing their secretory potential and possible tumor origin. Thus, our data suggest that both miR-148b and miR-133a have potential use as biomarkers for breast cancer detection.
EVALuna2:17449

Circulating tumor cells in metastatic breast cancer: clinical relevance and biological potential - Arkadius, Polasik; Marie, Tzschaschel; Fabienne, Schochter; Thomas, W. P. Friedl; Brigitte, Rack; Andreas, Hartkopf; Fasching, Peter; Andreas, Schneeweiss; Volkmar, Mueller; Jens, Huober; Wolfgang, Janni; Tanja, Fehm (Current Opinion in Obstetrics & Gynecology, 2019)
Purpose of review The possibility of tumor dissemination through the blood system has been known for years. Circulating tumor cells (CTCs) are detectable in the peripheral blood of patients with early as well as metastatic breast cancer. The prognostic relevance of this biomarker has already been described. By the use of repeated blood sampling along the course of disease, CTCs can be monitored in terms of a regular 'liquid biopsy'. This review aims to summarize recent research findings and actual ongoing clinical studies to demonstrate the actual and future relevance of CTCs in daily clinical routine. Recent findings Recent research results show that additional molecular analysis of CTCs might be helpful in gaining information about tumor characteristics, tumor heterogeneity and possible therapy resistance. Repetitive invasive core biopsies might be avoided. The assessment of molecular attributes may be indispensable for obtaining an optimized and personalized therapy aiming at extended survival and/or improved quality of life.
CRIS-Team WoS Importer:2019-04-12

Circulating tumor cells predict survival in early average-to-high risk breast cancer patients - Rack, Brigitte; Schindlbeck, Christian; Jueckstock, Julia; Andergassen, Ulrich; Hepp, Philip; Zwingers, Thomas; Friedl, Thomas W. P.; Lorenz, Ralf; Tesch, Hans; Fasching, Peter; Fehm, Tanja; Schneeweiss, Andreas; et al. (Journal of the National Cancer Institute, 2014)
Circulating tumor cells (CTCs) have been shown to predict reduced survival outcomes in metastatic breast cancer.CTCs were analyzed in 2026 patients with early breast cancer before adjuvant chemotherapy and in 1492 patients after chemotherapy using the CellSearch System. After immuno-magnetic enrichment for cells expressing the epithelial-cell adhesion molecule, CTCs were defined as nucleated cells expressing cytokeratin and lacking CD45. The patients were followed for a median of 35 months (range = 0-54). Kaplan-Meier analyses and the log-rank test were used for survival analyses. All statistical tests were two-sided.Before chemotherapy, CTCs were detected in 21.5% of patients (n = 435 of 2026), with 19.6% (n = 136 of 692) of node-negative and 22.4% (n = 299 of 1334) of node-positive patients showing CTCs (P < .001). No association was found with tumor size, grading, or hormone receptor status. After chemotherapy, 22.1% of patients (n = 330 of 1493) were CTC positive. The presence of CTCs was associated with poor disease-free survival (DFS; P < .0001), distant DFS (P < .001), breast cancer-specific survival (P = .008), and overall survival (OS; P = .0002). CTCs were confirmed as independent prognostic markers in multivariable analysis for DFS (hazard ratio [HR] = 2.11; 95% confidence interval [CI] = 1.49 to 2.99; P < .0001) and OS (HR = 2.18; 95% CI = 1.32 to 3.59; P = .002). The prognosis was worst in patients with at least five CTCs per 30 mL blood (DFS: HR = 4.51, 95% CI = 2.59 to 7.86; OS: HR = 3.60, 95% CI = 1.56 to 8.45). The presence of persisting CTCs after chemotherapy showed a negative influence on DFS (HR = 1.12; 95% CI = 1.02 to 1.25; P = .02) and on OS (HR = 1.16; 95% CI = 0.99 to 1.37; P = .06) CONCLUSIONS: These results suggest the independent prognostic relevance of CTCs both before and after adjuvant chemotherapy in a large prospective trial of patients with primary breast cancer.
EVALuna2:17454

Circulating Tumour Cells, Circulating Tumour DNA and Circulating MicroRNA in Metastatic Breast Carcinoma - What is the Role of Liquid Biopsy in Breast Cancer? - Polasik, Arkadius; Tzschaschel, Marie; Schochter, Fabienne; De Gregorio, Amelie; Friedl, Thomas W. P.; Rack, Brigitte; Hartkopf, Andreas; Fasching, Peter; Schneeweiss, Andreas; Mueller, Volkmar; Huober, Jens; Janni, Wolfgang; et al. (Geburtshilfe und Frauenheilkunde, 2017)
Dissemination of tumour cells and the development of solid metastases occurs via blood vessels and lymphatics. Circulating tumour cells (CTCs) and circulating tumour DNA (ctDNA) can be detected in venous blood in patients with early and metastatic breast cancer, and their prognostic relevance has been demonstrated on numerous occasions. Repeated testing for CTCs and ctDNA, or regular so-called "liquid biopsy", can be performed easily at any stage during the course of disease. Additional molecular analysis allows definition of tumour characteristics and heterogeneity that may be associated with treatment resistance. This in turn makes personalised, targeted treatments possible that may achieve both improved overall survival and quality of life.
EVALuna2:36179

Cis-eQTL analysis and functional validation of candidate susceptibility genes for high-grade serous ovarian cancer - Lawrenson, Kate; Li, Qiyan; Kar, Siddhartha; Seo, Ji-Heui; Tyrer, Jonathan; Spindler, Tassja J.; Lee, Janet; Chen, Yibu; Karst, Alison; Drapkin, Ronny; Aben, Katja K. H.; Anton-Culver, Hoda; et al. (Nature Communications, 2015)
Genome-wide association studies have reported 11 regions conferring risk of high-grade serous epithelial ovarian cancer (HGSOC). Expression quantitative trait locus (eQTL) analyses can identify candidate susceptibility genes at risk loci. Here we evaluate cis-eQTL associations at 47 regions associated with HGSOC risk (P<=10(-5)). For three cis-eQTL associations (P<1.4 × 10(-3), FDR<0.05) at 1p36 (CDC42), 1p34 (CDCA8) and 2q31 (HOXD9), we evaluate the functional role of each candidate by perturbing expression of each gene in HGSOC precursor cells. Overexpression of HOXD9 increases anchorage-independent growth, shortens population-doubling time and reduces contact inhibition. Chromosome conformation capture identifies an interaction between rs2857532 and the HOXD9 promoter, suggesting this SNP is a leading causal variant. Transcriptomic profiling after HOXD9 overexpression reveals enrichment of HGSOC risk variants within HOXD9 target genes (P=6 × 10(-10) for risk variants (P<10(-4)) within 10 kb of a HOXD9 target gene in ovarian cells), suggesting a broader role for this network in genetic susceptibility to HGSOC.
EVALuna2:9265

Clarifications concerning the commentary "published analysis of contraceptive effectiveness of Daysy and DaysyView app is fatally flawed" - Koch, Martin; Lermann, Johannes; Van De Roemer, Niels; Renner, Simone K.; Burghaus, Stefanie; Hackl, Janina; Dittrich, Ralf; Kehl, Sven; Oppelt, Patricia; Hildebrandt, Thomas; Hack, Caroline; Poehls, Uwe G.; et al. (Reproductive Health, 2019)
CRIS-Team Scopus Importer:2019-07-02

Clinical and analytical validation of Ki-67 in 9069 patients from IBCSG VIII + IX, BIG1-98 and GeparTrio trial: systematic modulation of interobserver variance in a comprehensive in silico ring trial - Denkert, Carsten; Budczies, Jan; Regan, Meredith M.; Loibl, Sibylle; Dell’Orto, Patrizia; von Minckwitz, Gunter; Mastropasqua, Mauro G.; Solbach, Christine; Thürlimann, Beat; Mehta, Keyur; Blohmer, Jens Uwe; Colleoni, Marco; et al. (Breast Cancer Research and Treatment, 2019)
Purpose: Ki-67 has been clinically validated for risk assessment in breast cancer, but the analytical validation and cutpoint-definition remain a challenge. Intraclass correlation coefficients (ICCs) are a statistical parameter for Ki-67 interobserver performance. However, the maximum degree of variance among pathologists allowed for meaningful biomarker results has not been defined. Methods: Different amounts of variance were added to central pathology Ki-67 data (n = 9069) from three cohorts (IBCSGVIII + IX, BIG1-98, GeparTrio) by simulation of 4500 evaluations for each cohort, which were grouped by ICCs, ranging from excellent (ICC = 0.9) to poor concordance (ICC = 0.1). Endpoints were disease-free survival (DFS) and pathological complete response (pCR, GeparTrio). Results: Ki-67 was a significant continuous prognostic marker for DFS over a wide range of cutpoints between 8% and 30% in all three cohorts. In our modelling approach, Ki-67 was a stable prognostic marker despite increased interpathologist variance. Even for a poor ICC of 0.5, one or more significant Ki-67 cutoffs were detected in 86.8% (GeparTrio), 92.4% (IBCSGVIII + IX) and 100% of analyses (BIG1-98). Similarly, in GeparTrio, even with an extremely low ICC of 0.2, 99.6% of analyses were significant for pCR. Conclusions: Our study shows that Ki-67 is a continuous marker which is extremely robust to pathologist variation. Even if only 50% of variance is attributable to true Ki-67-based proliferation (ICC = 0.5), this information is sufficient to obtain statistically significant differences in clinical cohorts. This stable performance explains the observation that many Ki-67 studies achieve significant results despite relevant interobserver variance and points to a high clinical validity of this biomarker. For clinical decisions based on analysis of individual patient data, ongoing efforts to further reduce interobserver variability, including ring trials and standardized guidelines as well as image analysis approaches, should be continued.
CRIS-Team Scopus Importer:2019-05-21
Keywords: Adjuvant; Breast cancer; Ki-67; Neoadjuvant; Prediction; Prognosis

Clinical and molecular characteristics of HER2-low-positive breast cancer: pooled analysis of individual patient data from four prospective, neoadjuvant clinical trials - Denkert, Carsten; Seither, Fenja; Schneeweiss, Andreas; Link, Theresa; Blohmer, Jens Uwe; Just, Marianne; Wimberger, Pauline; Forberger, Almuth; Tesch, Hans; Jackisch, Christian; Schmatloch, Sabine; Reinisch, Mattea; et al. (The Lancet. Oncology, 2021)
Background: The development of anti-HER2 antibody–drug conjugates opens new therapeutic options for patients with breast cancer, including patients with low expression of HER2. To characterise this new breast cancer subtype, we have compared the clinical and molecular characteristics of HER2-low-positive and HER2-zero breast cancer, including response to neoadjuvant chemotherapy and prognosis. Methods: In this pooled analysis of individual patient data, we evaluated a cohort of 2310 patients with HER2-non-amplified primary breast cancer that were treated with neoadjuvant combination chemotherapy in four prospective neoadjuvant clinical trials (GeparSepto, NCT01583426; GeparOcto, NCT02125344; GeparX, NCT02682693; Gain-2 neoadjuvant, NCT01690702) between July 30, 2012, and March 20, 2019. Central HER2 testing was done prospectively before random assignment of participants in all trials. HER2-low-positive status was defined as immunohistochemistry (IHC) 1+ or IHC2+/in-situ hybridisation negative and HER2-zero was defined as IHC0, based on the American Society of Clinical Oncology/College of American Pathologists guidelines. Disease-free survival and overall survival data were available for 1694 patients (from all trials except GeparX) with a median follow-up of 46·6 months (IQR 35·0–52·3). Bivariable and multivariable logistic regression models and Cox-proportional hazards models were performed based on a predefined statistical analysis plan for analysis of the endpoints pathological complete response, disease-free survival, and overall survival. Findings: A total of 1098 (47·5%) of 2310 tumours were HER2-low-positive and 1212 (52·5%) were HER2-zero. 703 (64·0%) of 1098 patients with HER2-low-positive tumours were hormone receptor positive, compared with 445 (36·7%) of 1212 patients with HER2-zero tumours (p<0.0001). HER2-low-positive tumours had a significantly lower pathological complete response rate than HER2-zero tumours (321 [29·2%] of 1098 vs 473 [39·0%] of 1212, p=0·0002). Pathological complete response was also significantly lower in HER2-low-positive tumours versus HER2-zero tumours in the hormone receptor-positive subgroup (123 [17·5%] of 703 vs 105 [23·6%] of 445, p=0·024), but not in the hormone receptor-negative subgroup (198 [50·1%] of 395 vs 368 [48·0%] of 767, p=0·21). Patients with HER2-low-positive tumours had significantly longer survival than did patients with HER2-zero tumours (3-year disease-free survival: 83·4% [95% CI 80·5–85·9] vs 76·1% [72·9–79·0]; stratified log-rank test p=0·0084; 3-year overall survival: 91·6% [84·9–93·4] vs 85·8% [83·0–88·1]; stratified log-rank test p=0·0016). Survival differences were also seen in patients with hormone receptor-negative tumours (3-year disease-free survival: 84·5% [95% CI 79·5–88·3] vs 74·4% [70·2–78.0]; stratified log-rank test p=0·0076; 3-year overall survival: 90·2% [86·0–93·2] vs 84·3% [80·7–87·3], stratified log-rank test p=0·016), but not in patients with hormone receptor-positive tumours (3-year disease-free survival 82·8% [79·1–85·9] vs 79·3% [73·9–83·7]; stratified log-rank test p=0·39; 3-year overall survival 92·3% [89·6–94·4] vs 88·4% [83·8–91·8]; stratified log-rank test p=0·13). Interpretation: Our results show that HER2-low-positive tumours can be identified as new subgroup of breast cancer by standardised IHC, distinct from HER2-zero tumours. HER2-low-positive tumours have a specific biology and show differences in response to therapy and prognosis, which is particularly relevant in therapy-resistant, hormone receptor-negative tumours. Our results provide a basis for a better understanding of the biology of breast cancer subtypes and the refinement of future diagnostic and therapeutic strategies. Funding: German Cancer Aid (Deutsche Krebshilfe).
CRIS-Team Scopus Importer:2021-08-20

Clinical and pathological associations of PTEN expression in ovarian cancer: a multicentre study from the Ovarian Tumour Tissue Analysis Consortium - Martins, Filipe Correia; Couturier, Dominique Laurent; Paterson, Anna; Karnezis, Anthony N.; Chow, Christine; Nazeran, Tayyebeh M.; Odunsi, Adekunle; Gentry-Maharaj, Aleksandra; Vrvilo, Aleksandra; Hein, Alexander; Talhouk, Aline; Osorio, Ana; et al. (British Journal of Cancer, 2020)
Background: PTEN loss is a putative driver in histotypes of ovarian cancer (high-grade serous (HGSOC), endometrioid (ENOC), clear cell (CCOC), mucinous (MOC), low-grade serous (LGSOC)). We aimed to characterise PTEN expression as a biomarker in epithelial ovarian cancer in a large population-based study. Methods: Tumours from 5400 patients from a multicentre observational, prospective cohort study of the Ovarian Tumour Tissue Analysis Consortium were used to evaluate associations between immunohistochemical PTEN patterns and overall survival time, age, stage, grade, residual tumour, CD8+ tumour-infiltrating lymphocytes (TIL) counts, expression of oestrogen receptor (ER), progesterone receptor (PR) and androgen receptor (AR) by means of Cox proportional hazard models and generalised Cochran–Mantel–Haenszel tests. Results: Downregulation of cytoplasmic PTEN expression was most frequent in ENOC (most frequently in younger patients; p value = 0.0001) and CCOC and was associated with longer overall survival in HGSOC (hazard ratio: 0.78, 95% CI: 0.65–0.94, p value = 0.022). PTEN expression was associated with ER, PR and AR expression (p values: 0.0008, 0.062 and 0.0002, respectively) in HGSOC and with lower CD8 counts in CCOC (p value < 0.0001). Heterogeneous expression of PTEN was more prevalent in advanced HGSOC (p value = 0.019) and associated with higher CD8 counts (p value = 0.0016). Conclusions: PTEN loss is a frequent driver in ovarian carcinoma associating distinctly with expression of hormonal receptors and CD8+ TIL counts in HGSOC and CCOC histotypes.
CRIS-Team Scopus Importer:2020-06-26

Clinical and Surgical Evaluation of Sentinel Node Biopsy in Patients with Early-Stage Endometrial Cancer and Atypical Hyperplasia - Pöschke, Patrik; Gaß, Paul; Krückel, Annika; Keller, Katharina; Erber, Ramona; Hartmann, Arndt; Beckmann, Matthias; Emons, Julius (Geburtshilfe und Frauenheilkunde, 2024)
Introduction The medical and surgical treatment of endometrial cancer (EC) is evolving toward a more patient-centered and personalized approach. The role of laparoscopic sentinel node biopsy (SNB) for early-stage EC is unclear, and very few data are available for atypical endometrial hyperplasia (AEH). The present study investigated the effectiveness of SNB combined with laparoscopic hysterectomy in patients with early-stage EC and AEH. Patients and Methods This was a retrospective, single-center cohort study for the period from January 2018 to December 2023. A total of 102 patients with atypical hyperplasia (n = 20) and early-stage EC (n = 82) findings on diagnostic curettage underwent pelvic sentinel node biopsy during the final operation. Results Eleven patients (55%) who had initially been diagnosed with AEH were found to have EC in the final pathology report. No lymph node metastases were detected in patients who had initially been diagnosed with AEH; a 3.6% rate of positive SNBs was found in patients with EC. Changes in tumor grade occurred in 31.3% of the patients and changes in FIGO stage in 33%. Bilateral sentinel node (SN) mapping was successful in 94.1% of the patients. The postoperative outcomes were comparable to those of routine clinical practice without SNB. Conclusions SNB can be safely offered to patients who have precursor lesions and early-stage EC without notably extending surgical times or increasing postoperative morbidity. This approach can be considered and is safe for patients diagnosed with AEH, but it appears to have a rather small impact on these patients.
CRIS-Team Scopus Importer:2024-06-14
Keywords: atypical endometrial hyperplasia; endometrial cancer; indocyanine green; sentinel node biopsy; surgery

Clinical Characteristics and Prognosis of HER2-0 and HER2-Low-Positive Breast Cancer Patients: Real-World Data from Patients Treated with Neoadjuvant Chemotherapy - Pöschke, Patrik; Fasching, Peter; Adler, Werner; Rübner, Matthias; Beckmann, Matthias; Hack, Carolin; Heindl, Felix; Hartmann, Arndt; Erber, Ramona; Gaß, Paul (Cancers, 2023)
In our study, we observed the long-term survival outcomes investigated for HER2-0 and HER2-low-positive breast cancer patients who received neoadjuvant chemotherapy. Between 1998 and 2020, 10,333 patients with primary breast cancer were treated, including 1373 patients with HER2-0 or HER2-low-positive disease with neoadjuvant chemotherapy. Descriptive analyses were performed, and logistic regression models and survival analyses were calculated for disease-free survival (DFS) and overall survival (OS). Among the 1373 patients, 930 (67.73%) had HER2-low-positive and 443 (32.27%) had HER2-0 tumors. Patients with HER2-0 tumors had a significantly better pathological complete response, 29.25% vs. 20.09%, and pathological complete response/in situ, 31.97% vs. 24.08%, than patients with HER2-low-positive tumors (p < 0.001; p = 0.003), regardless of the hormone receptor (HR) status. No statistically significant differences were observed for the HR-positive (p = 0.315; p = 0.43) or HR-negative subgroups (p = 0.573; p = 0.931). DFS and OS were significantly longer for HR-positive, HER2-low-positive patients (log-rank p = 0.02; p = 0.012). OS was significantly longer for HR-negative, HER2-0 patients (log-rank p = 0.032). No significant DFS differences were found for the HR-negative cohort (log-rank p = 0.232). For the overall cohort, no significant differences were noted between HER2-low-positive and HER2-0 patients, either for DFS (log-rank p = 0.220) or OS (log-rank p = 0.403). These results show different survival outcomes for HER2-0 and HER2-low-positive tumors relative to HR status. These different cohorts can be identified using standardized immunohistochemistry, even retrospectively.
CRIS-Team Scopus Importer:2023-10-20
Keywords: breast cancer; HER2; HER2-0; HER2-low-positive; neoadjuvant therapy; prognosis

Clinical effectiveness and safety of olaparib in BRCA-mutated, HER2-negative metastatic breast cancer in a real-world setting: final analysis of LUCY - Balmaña, Judith; Fasching, Peter; Couch, Fergus J.; Delaloge, Suzette; Labidi-Galy, Intidhar; O’Shaughnessy, Joyce; Park, Yeon Hee; Eisen, Andrea F.; You, Benoit; Bourgeois, Hughes; Gonçalves, Anthony; Kemp, Zoe; et al. (Breast Cancer Research and Treatment, 2023)
Purpose: The interim analysis of the phase IIIb LUCY trial demonstrated the clinical effectiveness of olaparib in patients with germline BRCA-mutated (gBRCAm), human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer (mBC), with median progression-free survival (PFS) of 8.11 months, which was similar to that in the olaparib arm of the phase III OlympiAD trial (7.03 months). This prespecified analysis provides final overall survival (OS) and safety data. Methods: The open-label, single-arm LUCY trial of olaparib (300 mg, twice daily) enrolled adults with gBRCAm or somatic BRCA-mutated (sBRCAm), HER2-negative mBC. Patients had previously received a taxane or anthracycline for neoadjuvant/adjuvant or metastatic disease and up to two lines of chemotherapy for mBC. Results: Of 563 patients screened, 256 (gBRCAm, n = 253; sBRCAm, n = 3) were enrolled. In the gBRCAm cohort, median investigator-assessed PFS (primary endpoint) was 8.18 months and median OS was 24.94 months. Olaparib was clinically effective in all prespecified subgroups: hormone receptor status, previous chemotherapy for mBC, previous platinum-based chemotherapy (including by line of therapy), and previous cyclin-dependent kinase 4/6 inhibitor use. The most frequent treatment-emergent adverse events (TEAEs) were nausea (55.3%) and anemia (39.2%). Few patients (6.3%) discontinued olaparib owing to a TEAE. No deaths associated with AEs occurred during the study treatment or 30-day follow-up. Conclusion: The LUCY patient population reflects a real-world population in line with the licensed indication of olaparib in mBC. These findings support the clinical effectiveness and safety of olaparib in patients with gBRCAm, HER2-negative mBC. Clinical trial registration: Clinical trials registration number: NCT03286842.
CRIS-Team Scopus Importer:2023-12-29
Keywords: Breast cancer; Breast cancer 1 gene product; Breast cancer 2 gene product; Kaplan–Meier survival curves; Olaparib; Overall survival; Progression-free survival

Clinical effectiveness and safety of olaparib in BRCA-mutated, HER2-negative metastatic breast cancer in a real-world setting: Phase IIIb LUCY final analysis - Balmana, J.; Fasching, Peter; Delaloge, S.; Park, Y. H.; Eisen, A.; Bourgeois, H.; Kemp, Z.; Jankowski, T.; Sohn, J.; Aksoy, S.; Timcheva, C. V.; Park-Simon, T-W.; et al. (ANNALS OF ONCOLOGY, 2022)
CRIS-Team WoS Importer:2022-06-03

Clinical effectiveness of olaparib monotherapy in germline BRCA-mutated, HER2-negative metastatic breast cancer in a real-world setting: phase IIIb LUCY interim analysis - Gelmon, Karen A.; Fasching, Peter; Couch, Fergus J.; Balmaña, Judith; Delaloge, Suzette; Labidi-Galy, Intidhar; Bennett, James; McCutcheon, Susan; Walker, Graham; O'Shaughnessy, Joyce; Timcheva, Constanta; Tomova, Antoaneta; et al. (European Journal of Cancer, 2021)
Background: In the phase III OlympiAD trial, olaparib significantly increased progression-free survival (PFS) compared with chemotherapy of physician's choice in patients with germline BRCA-mutated (gBRCAm), human epidermal growth factor 2 (HER2)-negative metastatic breast cancer (mBC). The phase IIIb LUCY trial assessed the clinical effectiveness of olaparib in similar patients, in a setting reflecting clinical practice. Methods: This open-label, single-arm trial of olaparib (300 mg, twice daily) enrolled patients with BRCAm, HER2-negative mBC who had received taxane and/or anthracycline in the (neo)adjuvant/metastatic setting and not more than two lines of prior chemotherapy for mBC. Patients with hormone receptor–positive mBC had progressed on at least one line of endocrine therapy in an adjuvant/metastatic setting and were unsuitable for further endocrine treatment. This interim analysis was planned after 160 PFS events. Results: Of 563 patients screened, 252 patients with gBRCAm were enrolled and received at least one dose of olaparib. The median investigator-assessed PFS was 8.11 months (95% confidence interval [CI], 6.93–8.67; 166/252 events [65.9% maturity]). The investigator-assessed clinical response rate was 48.6%, and median time to first subsequent treatment or death was 9.66 months (95% CI, 8.67–11.14). The most common treatment-emergent adverse events (TEAEs; >20% patients) were nausea, anaemia, asthenia, vomiting and fatigue. Eleven patients (4.4%) discontinued treatment because of a TEAE. Grade 3 or higher TEAEs occurred in 64 patients (25.4%), including anaemia (33 patients; 13.1%). Conclusion: Olaparib was clinically effective in patients with gBRCAm, HER2-negative mBC with safety outcomes consistent with previous findings. ClinicalTrials.gov identifier: NCT03286842.
CRIS-Team Scopus Importer:2021-06-18
Keywords: BRCA1 gene; BRCA2 gene; Breast cancer; Effectiveness; Germline mutation; Metastatic; Olaparib; Progression-free survival; Treatment outcome

Clinical parameters affecting survival outcomes in patients with low-grade serous ovarian carcinoma: An international multicentre analysis - May, Taymaa; Bernardini, Marcus; Lheureux, Stephanie; Aben, Katja K.H.; Bandera, Elisa V.; Beckmann, Matthias; Benitez, Javier; Berchuck, Andrew; Bjørge, Line; Carney, Michael E.; Cramer, Daniel W.; Defazio, Anna; et al. (Canadian Medical Association Journal, 2023)
Background: Women with low-grade ovarian serous carcinoma (LGSC) benefit from surgical treatment; however, the role of chemotherapy is controversial. We examined an international database through the Ovarian Cancer Association Consortium to identify factors that affect survival in LGSC. Methods: We performed a retrospective cohort analysis of patients with LGSC who had had primary surgery and had overall survival data available. We performed univariate and multivariate analyses of progression-free survival and overall survival, and generated Kaplan-Meier survival curves. Results: Of the 707 patients with LGSC, 680 (96.2%) had available overall survival data. The patients' median age overall was 54 years. Of the 659 patients with International Federation of Obstetrics and Gynecology stage data, 156 (23.7%) had stage I disease, 64 (9.7%) had stage II, 395 (59.9%) had stage III, and 44 (6.7%) had stage IV. Of the 377 patients with surgical data, 200 (53.0%) had no visible residual disease. Of the 361 patients with chemotherapy data, 330 (91.4%) received first-line platinum-based chemotherapy. The median follow-up duration was 5.0 years. The median progression-free survival and overall survival were 43.2 months and 110.4 months, respectively. Multivariate analysis indicated a statistically significant impact of stage and residual disease on progression-free survival and overall survival. Platinum-based chemotherapy was not associated with a survival advantage. Conclusion: This multicentre analysis indicates that complete surgical cytoreduction to no visible residual disease has the most impact on improved survival in LGSC. This finding could immediately inform and change practice.
CRIS-Team Scopus Importer:2023-08-11

Clinical Relevance of Serum HER2 and Circulating Tumor Cell Detection in Metastatic Breast Cancer Patients - Banys-Paluchowski, Malgorzata; Witzel, Isabell; Riethdorf, Sabine; Rack, Brigitte; Janni, Wolfgang; Fasching, Peter; Solomayer, Erich-Franz; Aktas, Bahriye; Kasimir-Bauer, Sabine; Pantel, Klaus; Fehm, Tanja; Mueller, Volkmar (Anticancer Research, 2017)
BACKGROUND/AIM: Presence of circulating tumor cells (CTCs) is associated with impaired survival in metastatic breast cancer (MBC). This study was designed to evaluate whether assessment of serum HER2 (sHER2) levels provide additional prognostic information in MBC. MATERIALS AND METHODS: Two hundred and fifty-three MBC patients were enrolled in this multicentre trial. CTCs were detected before the start of first- or later-line treatment using the CellSearch system. sHER2 was determined using ELISA. RESULTS: ≥5 CTCs were detected in 122 of 245 evaluable patients (49.8%). One hundred and nineteen of 251 patients (47%) had sHER2 levels above 15 ng/ml. Median overall survival (OS) was 16.3 months in patients with elevated sHER2; median OS in patients with non-elevated sHER2 has not been reached (p=0.001). Patients with ≥5 CTCs were more likely to present with elevated sHER2 (61% vs. 33% in those with <5 CTC; p<0.001). In patients with HER2-negative tumors, elevated sHER2 was associated with shorter OS and PFS; in HER2-positive patients with OS only. Including sHER2, CTC status and established prognostic factors into a multivariate analysis, only the presence of CTCs and higher-line of therapy remained independent predictors of OS. CONCLUSION: Elevated levels of sHER2 are associated with worse survival, irrespective of the HER2 status of the tumor. However, sHER2 does not provide additional prognostic information in patients with known CTC status.
EVALuna2:36192

Clinical validation of genetic variants associated with in vitro chemotherapy-related lymphoblastoid cell toxicity - Fasching, Peter; Häberle, Lothar; Rack, Brigitte; Li, Liang; Hein, Alexander; Ekici, Arif Bülent; Reis, André; Lux, Michael P.; Cunningham, Julie M.; Rübner, Matthias; Jenkins, Gergory; Fridley, Brooke; et al. (Oncotarget, 2017)
Hematotoxicity is one of the major side effects of chemotherapy. The aim of this study was to examine the association between single nucleotide polymorphisms (SNPs) and hematotoxicity in breast cancer patients in a subset of patients of the SUCCESS prospective phase III chemotherapy study. All patients (n = 1678) received three cycles of 5-fluorouracil, epirubicin, and cyclophosphamide (FEC) followed by three cycles of docetaxel or docetaxel/gemcitabine, depending on randomization. Germline DNA was genotyped for 246 SNPs selected from a previous genome-wide association study (GWAS) in a panel of lymphoblastoid cell lines, with gemcitabine toxicity as the phenotype. All SNPs were tested for their value in predicting grade 3 or 4 neutropenic or leukopenic events (NLEs). Their prognostic value in relation to overall survival and disease-free survival was also tested. None of the SNPs was found to be predictive for NLEs during treatment with docetaxel/gemcitabine. Two SNPs in and close to the PIGB gene significantly improved the prediction of NLEs after FEC, in addition to the factors of age and body surface area. The top SNP (rs12050587) had an odds ratio of 1.38 per minor allele (95% confidence interval, 1.17 to 1.62). No associations were identified for predicting disease-free or overall survival. Genetic variance in the PIGB gene may play a role in determining interindividual differences in relation to hematotoxicity after FEC chemotherapy.
EVALuna2:9381

COGNITION-GUIDE - Genomics-Guided Targeted Post-Neoadjuvant Therapy in Patients with Early Breast Cancer: Study Design of a Multicenter, Open-Label, Umbrella Phase II Study - Pixberg, Constantin; Maurer, Christian; Smetanay, Katharina; Straβl, Luise; Hlevnjak, Mario; Zapatka, Marc; Wagner, Celina V.; Yazdanparast, Haniyeh; Kurzawa, Johanna; Erben, Vanessa; Feng, Fangyoumin; Hong, Chen; et al. (Geburtshilfe und Frauenheilkunde, 2025)
Background As part of the COGNITION diagnostic registry program, residual tumor material after neoadjuvant therapy (NAT) of patients with early breast cancer (eBC), who are still at high-risk for relapse after NAT, is analyzed by next generation sequencing to identify biomarkers and actionable alterations. This strategy aims to stratify patients for subsequent genomics-guided therapies to reduce the significant risk of metastatic dissemination and hence to improve disease-free survival. Patients and Methods COGNITION-GUIDE is a multicenter umbrella phase-II-trial to translate molecular biomarker profiles generated in the COGNITION platform into six molecular-guided post-neoadjuvant therapeutic options in addition to standard-of-care treatment. Patients can be allocated to immune checkpoint inhibition (PD-L1-antibody), PI3K inhibition, AKT inhibition, PARP inhibition, anti-Trop-2 antibody-drug-conjugate, HER2 inhibition or, in case of missing biomarkers, to observation for 12 months. The primary endpoint is invasive disease-free survival (IDFS) four years after surgery. Secondary endpoints include IDFS in each study arm separately, distant disease-free survival, overall survival and safety. 240 patients will be enrolled within four years. Conclusions The COGNITION-GUIDE trial, which was activated in June 2023 and will recruit in different centers in Germany, empowers a risk-adapted, biomarker-guided therapy escalation algorithm in eBC patients who are still at high risk of metastasis.
CRIS-Team Scopus Importer:2025-05-02
Keywords: clinical trial in progress; early breast cancer; precision oncology; targeted therapy

Collective forces of tumor spheroids in three-dimensional biopolymer networks - Mark, Christoph; Grundy, Thomas J.; Strissel, Pamela; Böhringer, David; Grummel, Nadine; Gerum, Richard; Steinwachs, Julian; Hack, Carolin; Beckmann, Matthias; Eckstein, Markus; Strick, Reiner; O'Neill, Geraldine M.; et al. (eLife, 2020)
We describe a method for quantifying the contractile forces that tumor spheroids collectively exert on highly nonlinear three-dimensional collagen networks. While three-dimensional traction force microscopy for single cells in a nonlinear matrix is computationally complex due to the variable cell shape, here we exploit the spherical symmetry of tumor spheroids to derive a scale-invariant relationship between spheroid contractility and the surrounding matrix deformations. This relationship allows us to directly translate the magnitude of matrix deformations to the total contractility of arbitrarily sized spheroids. We show that our method is accurate up to strains of 50% and remains valid even for irregularly shaped tissue samples when considering only the deformations in the far field. Finally, we demonstrate that collective forces of tumor spheroids reflect the contractility of individual cells for up to 1 hr after seeding, while collective forces on longer timescales are guided by mechanical feedback from the extracellular matrix.
CRIS-Team WoS Importer:2020-05-22

Combination of an ultrafast TWIST-VIBE Dixon sequence protocol and diffusion-weighted imaging into an accurate easily applicable classification tool for masses in breast MRI - Peter, Sandra C.; Wenkel, Evelyn; Weiland, Elisabeth; Dietzel, Matthias; Janka, Rolf Matthias; Hartmann, Arndt; Emons, Julius; Uder, Michael; Ellmann, Stephan (European Radiology, 2020)
Objectives: This study aimed to develop a tool for the classification of masses in breast MRI, based on ultrafast TWIST-VIBE Dixon (TVD) dynamic sequences combined with DWI. TVD sequences allow to abbreviate breast MRI protocols, but provide kinetic information only on the contrast wash-in, and because of the lack of the wash-out kinetics, their diagnostic value might be hampered. A special focus of this study was thus to maintain high diagnostic accuracy in lesion classification. Materials and methods: Sixty-one patients who received breast MRI between 02/2014 and 04/2015 were included, with 83 reported lesions (60 malignant). Our institute’s standard breast MRI protocol was complemented by an ultrafast TVD sequence. ADC and peak enhancement of the TVD sequences were integrated into a generalised linear model (GLM) for malignancy prediction. For comparison, a second GLM was calculated using ADC and conventional DCE curve type. The resulting GLMs were evaluated for standard diagnostic parameters. For easy application of the GLMs, nomograms were created. Results: The GLM based on peak enhancement of the TVD and ADC was as equally accurate as the GLM based on conventional DCE and ADC, with no significant differences (sensitivity, 93.3%/93.3%; specificity, 91.3%/87.0%; PPV, 96.6%/94.9%; NPV, 84.0%/83.3%; all, p ≥ 0.315). Conclusions: This study presents a method to integrate ultrafast TVD sequences into a breast MRI protocol, allowing a reduction of the examination time while maintaining diagnostic accuracy. A GLM based on the combination of TVD-derived peak enhancement and ADC provides high diagnostic accuracy, and can be easily applied using a nomogram. Key Points: • Ultrafast TWIST-VIBE Dixon sequence protocols in combination with diffusion-weighted imaging allow to shorten breast MRI examinations, while diagnostic accuracy is maintained. • Integrating peak enhancement from the TWIST-VIBE Dixon sequence and the apparent diffusion coefficient into a generalised linear model provides a comprehensible image evaluation approach. • This approach is further facilitated by nomograms.
CRIS-Team Scopus Importer:2020-02-11
Keywords: Breast cancer; Diagnostic imaging; Diffusion magnetic resonance imaging; Magnetic resonance imaging; Statistical model

Combined Associations of a Polygenic Risk Score and Classical Risk Factors With Breast Cancer Risk - Kapoor, Pooja Middha; Mavaddat, Nasim; Choudhury, Parichoy Pal; Wilcox, Amber N.; Lindström, Sara; Behrens, Sabine; Michailidou, Kyriaki; Dennis, Joe; Bolla, Manjeet K.; Wang, Qin; Jung, Audrey; Abu-Ful, Zomoroda; et al. (Journal of the National Cancer Institute, 2021)
We evaluated the joint associations between a new 313-variant PRS (PRS313) and questionnaire-based breast cancer risk factors for women of European ancestry, using 72 284 cases and 80 354 controls from the Breast Cancer Association Consortium. Interactions were evaluated using standard logistic regression and a newly developed case-only method for breast cancer risk overall and by estrogen receptor status. After accounting for multiple testing, we did not find evidence that per-standard deviation PRS313 odds ratio differed across strata defined by individual risk factors. Goodness-of-fit tests did not reject the assumption of a multiplicative model between PRS313 and each risk factor. Variation in projected absolute lifetime risk of breast cancer associated with classical risk factors was greater for women with higher genetic risk (PRS313 and family history) and, on average, 17.5% higher in the highest vs lowest deciles of genetic risk. These findings have implications for risk prevention for women at increased risk of breast cancer.
CRIS-Team Scopus Importer:2021-03-26

Common Genetic Variation In Cellular Transport Genes and Epithelial Ovarian Cancer (EOC) Risk - Chornokur, Ganna; Lin, Hui-Yi; Tyrer, Jonathan P.; Lawrenson, Kate; Dennis, Joe; Amankwah, Ernest K.; Qu, Xiaotao; Tsai, Ya-Yu; Jim, Heather S. L.; Chen, Zhihua; Chen, Ann Y.; Permuth-Wey, Jennifer; et al. (PLoS ONE, 2015)
Defective cellular transport processes can lead to aberrant accumulation of trace elements, iron, small molecules and hormones in the cell, which in turn may promote the formation of reactive oxygen species, promoting DNA damage and aberrant expression of key regulatory cancer genes. As DNA damage and uncontrolled proliferation are hallmarks of cancer, including epithelial ovarian cancer (EOC), we hypothesized that inherited variation in the cellular transport genes contributes to EOC risk.In total, DNA samples were obtained from 14,525 case subjects with invasive EOC and from 23,447 controls from 43 sites in the Ovarian Cancer Association Consortium (OCAC). Two hundred seventy nine SNPs, representing 131 genes, were genotyped using an Illumina Infinium iSelect BeadChip as part of the Collaborative Oncological Gene-environment Study (COGS). SNP analyses were conducted using unconditional logistic regression under a log-additive model, and the FDR q<0.2 was applied to adjust for multiple comparisons.The most significant evidence of an association for all invasive cancers combined and for the serous subtype was observed for SNP rs17216603 in the iron transporter gene HEPH (invasive: OR = 0.85, P = 0.00026; serous: OR = 0.81, P = 0.00020); this SNP was also associated with the borderline/low malignant potential (LMP) tumors (P = 0.021). Other genes significantly associated with EOC histological subtypes (p<0.05) included the UGT1A (endometrioid), SLC25A45 (mucinous), SLC39A11 (low malignant potential), and SERPINA7 (clear cell carcinoma). In addition, 1785 SNPs in six genes (HEPH, MGST1, SERPINA, SLC25A45, SLC39A11 and UGT1A) were imputed from the 1000 Genomes Project and examined for association with INV EOC in white-European subjects. The most significant imputed SNP was rs117729793 in SLC39A11 (per allele, OR = 2.55, 95% CI = 1.5-4.35, p = 5.66x10-4).These results, generated on a large cohort of women, revealed associations between inherited cellular transport gene variants and risk of EOC histologic subtypes.
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Common germline polymorphisms associated with breast cancer-specific survival - Pirie, Ailith; Guo, Qi; Kraft, Peter; Canisius, Sander; Eccles, Diana M.; Rahman, Nazneen; Nevanlinna, Heli; Chen, Constance; Khan, Sofia; Tyrer, Jonathan; Bolla, Manjeet K.; Wang, Qin; et al. (Breast Cancer Research, 2015)
Previous studies have identified common germline variants nominally associated with breast cancer survival. These associations have not been widely replicated in further studies. The purpose of this study was to evaluate the association of previously reported SNPs with breast cancer-specific survival using data from a pooled analysis of eight breast cancer survival genome-wide association studies (GWAS) from the Breast Cancer Association Consortium.A literature review was conducted of all previously published associations between common germline variants and three survival outcomes: breast cancer-specific survival, overall survival and disease-free survival. All associations that reached the nominal significance level of P value <0.05 were included. Single nucleotide polymorphisms that had been previously reported as nominally associated with at least one survival outcome were evaluated in the pooled analysis of over 37,000 breast cancer cases for association with breast cancer-specific survival. Previous associations were evaluated using a one-sided test based on the reported direction of effect.Fifty-six variants from 45 previous publications were evaluated in the meta-analysis. Fifty-four of these were evaluated in the full set of 37,954 breast cancer cases with 2,900 events and the two additional variants were evaluated in a reduced sample size of 30,000 samples in order to ensure independence from the previously published studies. Five variants reached nominal significance (P <0.05) in the pooled GWAS data compared to 2.8 expected under the null hypothesis. Seven additional variants were associated (P <0.05) with ER-positive disease.Although no variants reached genome-wide significance (P <5 x 10(-8)), these results suggest that there is some evidence of association between candidate common germline variants and breast cancer prognosis. Larger studies from multinational collaborations are necessary to increase the power to detect associations, between common variants and prognosis, at more stringent significance levels.
EVALuna2:9296

Common non-synonymous SNPs associated with breast cancer susceptibility: findings from the Breast Cancer Association Consortium - Milne, Roger L.; Burwinkel, Barbara; Michailidou, Kyriaki; Arias-Perez, Jose-Ignacio; Pilar Zamora, M.; Menendez-Rodriguez, Primitiva; Hardisson, David; Mendiola, Marta; Gonzalez-Neira, Anna; Pita, Guillermo; Rosario Alonso, M.; Dennis, Joe; et al. (Human Molecular Genetics, 2014)
Candidate variant association studies have been largely unsuccessful in identifying common breast cancer susceptibility variants, although most studies have been underpowered to detect associations of a realistic magnitude. We assessed 41 common non-synonymous single-nucleotide polymorphisms (nsSNPs) for which evidence of association with breast cancer risk had been previously reported. Case-control data were combined from 38 studies of white European women (46 450 cases and 42 600 controls) and analyzed using unconditional logistic regression. Strong evidence of association was observed for three nsSNPs: ATXN7-K264R at 3p21 [rs1053338, per allele OR = 1.07, 95% confidence interval (CI) = 1.04-1.10, P = 2.9 × 10(-6)], AKAP9-M463I at 7q21 (rs6964587, OR = 1.05, 95% CI = 1.03-1.07, P = 1.7 × 10(-6)) and NEK10-L513S at 3p24 (rs10510592, OR = 1.10, 95% CI = 1.07-1.12, P = 5.1 × 10(-17)). The first two associations reached genome-wide statistical significance in a combined analysis of available data, including independent data from nine genome-wide association studies (GWASs): for ATXN7-K264R, OR = 1.07 (95% CI = 1.05-1.10, P = 1.0 × 10(-8)); for AKAP9-M463I, OR = 1.05 (95% CI = 1.04-1.07, P = 2.0 × 10(-10)). Further analysis of other common variants in these two regions suggested that intronic SNPs nearby are more strongly associated with disease risk. We have thus identified a novel susceptibility locus at 3p21, and confirmed previous suggestive evidence that rs6964587 at 7q21 is associated with risk. The third locus, rs10510592, is located in an established breast cancer susceptibility region; the association was substantially attenuated after adjustment for the known GWAS hit. Thus, each of the associated nsSNPs is likely to be a marker for another, non-coding, variant causally related to breast cancer risk. Further fine-mapping and functional studies are required to identify the underlying risk-modifying variants and the genes through which they act.
EVALuna2:9242

Common variants at the CHEK2 gene locus and risk of epithelial ovarian cancer - Lawrenson, Kate; Iversen, Edwin S.; Tyrer, Jonathan; Weber, Rachel Palmieri; Concannon, Patrick; Hazelett, Dennis J.; Li, Qiyuan; Marks, Jeffrey R.; Berchuck, Andrew; Lee, Janet M.; Aben, Katja K. H.; Anton-Culver, Hoda; et al. (Carcinogenesis, 2015)
Genome-wide association studies have identified 20 genomic regions associated with risk of epithelial ovarian cancer (EOC), but many additional risk variants may exist. Here, we evaluated associations between common genetic variants [single nucleotide polymorphisms (SNPs) and indels] in DNA repair genes and EOC risk. We genotyped 2896 common variants at 143 gene loci in DNA samples from 15 397 patients with invasive EOC and controls. We found evidence of associations with EOC risk for variants at FANCA, EXO1, E2F4, E2F2, CREB5 and CHEK2 genes (P <= 0.001). The strongest risk association was for CHEK2 SNP rs17507066 with serous EOC (P = 4.74 x 10(-7)). Additional genotyping and imputation of genotypes from the 1000 genomes project identified a slightly more significant association for CHEK2 SNP rs6005807 (r (2) with rs17507066 = 0.84, odds ratio (OR) 1.17, 95% CI 1.11-1.24, P = 1.1×10(-7)). We identified 293 variants in the region with likelihood ratios of less than 1:100 for representing the causal variant. Functional annotation identified 25 candidate SNPs that alter transcription factor binding sites within regulatory elements active in EOC precursor tissues. In The Cancer Genome Atlas dataset, CHEK2 gene expression was significantly higher in primary EOCs compared to normal fallopian tube tissues (P = 3.72×10(-8)). We also identified an association between genotypes of the candidate causal SNP rs12166475 (r (2) = 0.99 with rs6005807) and CHEK2 expression (P = 2.70×10(-8)). These data suggest that common variants at 22q12.1 are associated with risk of serous EOC and CHEK2 as a plausible target susceptibility gene.
EVALuna2:9297

Comparative analysis of tumour mutational burden (TMB) prediction methods and its association with determinants of the tumour immune microenvironment of urothelial bladder cancer (UBC) - Eckstein, Markus; Hartmann, Arndt; Strissel, Pamela; Strick, Reiner; Wach, S.; Taubert, Helge; Wullich, Bernd; Geppert, Carol-Immanuel; Weyerer, Veronika; Stöhr, Robert; Rübner, Matthias; Fasching, Peter; et al. (ANNALS OF ONCOLOGY, 2019)
CRIS-Team WoS Importer:2019-11-08

Comparative assessment of breast volume using a smartphone device versus MRI - Behrens, Annika; Hübner, Hanna; Häberle, Lothar; Stamminger, Marc; Zint, Daniel; Heindl, Felix; Emons, Julius; Hack, Carolin; Nabieva, Naiba; Uder, Michael; Wetzl, Matthias; Wunderle, Marius; et al. (Breast Cancer, 2024)
Background: Assessment of breast volume has a relevance for aesthetic surgery and for the prevention and prediction of breast diseases. This study investigated breast volume measurements using a three-dimensional (3D) body surface scanner integrated in a smartphone device in comparison with magnetic resonance imaging (MRI) scans. Methods: Breast volume was assessed for 22 women who underwent routine MRI imaging. 3D surface images were acquired using a smartphone’s digital texture camera (iPhone 11 Pro Max, Apple, California, USA, 2019). Breast volumes were manually outlined and calculated by two independent investigators using a 3D software tool (Meshmixer 3.5, Autodesk, Inc., 2018). Volume assessments from MRI images were performed by a radiologist using Syngo.via (Siemens Healthcare, Erlangen, Germany, VB50). The agreement between both methods and the inter-observer agreement was calculated with the concordance correlation coefficients and analysed with Bland–Altman plots. Results: The mean breast volume as determined by MRI volumetry was 771.0 ml on the left side and 763.9 ml on the right side. Utilizing the 3D body surface volume assessment method, the mean breast volume was measured as 660.3 ml (observer A) and 616.8 ml (observer B) on the left side, and 701.9 ml (observer A) and 638.6 ml (observer B) on the right side. Although a high correlation was observed, differences in volume measurements appeared more pronounced in cases of larger breast volume. Conclusions: Smartphone-based 3D assessment of breast volume sufficiently agreed with MRI-based breast volume. This new technique could be used for cosmetic breast assessments in a surgical context and possibly in breast cancer risk studies assessing breast volume as outcome parameters.
CRIS-Team Scopus Importer:2024-11-22
Keywords: Breast volume; MRI; Smartphone; Three-dimensional (3D)

Comparative effectiveness of ribociclib plus fulvestrant (RIB plus FUL) versus palbociclib plus letrozole (PAL plus LET) as first-line (1L) treatment (Tx) of HR+/HER2L advanced breast cancer (ABC) assessed by matching-adjusted indirect comparison (MAIC) - Fasching, Peter; Delea, T.; Lu, Y-S.; Deboer, R.; Hurvitz, S. A.; Moynahan, A.; Chandiwana, D.; Lanoue, B.; Hu, H.; Thuerigen, A.; O'Shaughnessy, J. (ANNALS OF ONCOLOGY, 2020)
CRIS-Team WoS Importer:2020-10-30

Comparison of 6q25 breast cancer hits from Asian and European genome wide association studies in the Breast Cancer Association consortium (BCAC) - Hein, Rebecca; Maranian, Melanie; Hopper, John L.; Kapuscinski, Miroslaw K.; Southey, Melissa C.; Park, Daniel J.; Schmidt, Marjanka K.; Broeks, Annegien; Hogervorst, Frans B. L.; Bueno-De-Mesquit, H. Bas; Muir, Kenneth R.; Lophatananon, Artitaya; et al. (PLoS ONE, 2012)
The 6q25.1 locus was first identified via a genome-wide association study (GWAS) in Chinese women and marked by single nucleotide polymorphism (SNP) rs2046210, approximately 180 Kb upstream of ESR1. There have been conflicting reports about the association of this locus with breast cancer in Europeans, and a GWAS in Europeans identified a different SNP, tagged here by rs12662670. We examined the associations of both SNPs in up to 61,689 cases and 58,822 controls from forty-four studies collaborating in the Breast Cancer Association Consortium, of which four studies were of Asian and 39 of European descent. Logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI). Case-only analyses were used to compare SNP effects in Estrogen Receptor positive (ER+) versus negative (ER-) tumours. Models including both SNPs were fitted to investigate whether the SNP effects were independent. Both SNPs are significantly associated with breast cancer risk in both ethnic groups. Per-allele ORs are higher in Asian than in European studies [rs2046210: OR (A/G) = 1.36 (95% CI 1.26-1.48), p = 7.6×10-14 in Asians and 1.09 (95% CI 1.07-1.11), p = 6.8×10-18 in Europeans. rs12662670: OR (G/T) = 1.29 (95% CI 1.19-1.41), p = 1.2×10-9 in Asians and 1.12 (95% CI 1.08-1.17), p = 3.8×10-9 in Europeans]. SNP rs2046210 is associated with a significantly greater risk of ER- than ER+ tumours in Europeans [OR (ER-) = 1.20 (95% CI 1.15-1.25), p = 1.8×10-17 versus OR (ER+) = 1.07 (95% CI 1.04-1.1), p = 1.3×10-7, pheterogeneity = 5.1×10-6]. In these Asian studies, by contrast, there is no clear evidence of a differential association by tumour receptor status. Each SNP is associated with risk after adjustment for the other SNP. These results suggest the presence of two variants at 6q25.1 each independently associated with breast cancer risk in Asians and in Europeans. Of these two, the one tagged by rs2046210 is associated with a greater risk of ER- tumours. © 2012 Hein et al.
CRIS-Team Scopus Importer:2021-07-19

Comparison of C-Reactive Protein in Dried Blood Spots and Saliva of Healthy Adolescents - Plank, Anne-Christine; Maschke, Janina; Rohleder, Nicolas; Fasching, Peter; Beckmann, Matthias; Kornhuber, Johannes; Eichler, Anna; Moll, Gunther; Kratz, Oliver (Frontiers in Immunology, 2021)
Background/AimDetermining C-reactive protein (CRP) by non-invasive methods is of great interest for research addressing inflammation in young people. However, direct comparisons of such methods applied in children and adolescents are lacking so far. This study aimed to evaluate the association between CRP measured in dried blood spots (DBS CRP) and in saliva (sCRP), two less invasive alternatives to venipuncture, in 12- to 14-year-old adolescents. To evaluate the validity of both measurements in the context of biobehavioral studies, the potential of DBS CRP and sCRP to discriminate between defined BMI subgroups was assessed. Materials and MethodsCRP levels in DBS and saliva collected from 87 healthy adolescents (M = 13.25 years, SD = 0.30, 51.7% females) were determined using high sensitive CRP ELISA for serum and salivary CRP ELISA, respectively. Characteristics and correlation of both measurements were assessed for the total sample and for three subgroups classified by BMI percentile ranges (A: <= 25; B: 26-74; C: >= 75). ResultsIn the total sample, DBS CRP and sCRP were significantly associated (r = 0.59, p < 0.001). Splitting the sample into BMI-dependent subgroups revealed similarly strong associations of DBS CRP with sCRP for all three groups (A: r = 0.51; B: r = 0.61; C: r = 0.53). However, comparing the mean CRP values per BMI subgroup, one-way ANOVA reported significant differences for DBS CRP, but not for sCRP mean values. ConclusionsThe significant correlation of DBS CRP with sCRP was independent of the investigated BMI range groups, yet BMI-dependent distinction was only provided by DBS CRP mean values. Overall, our results suggest that DBS CRP is likely to reflect systemic inflammation more precisely. Salivary CRP can be alternatively determined in studies with adolescents when conditions require it, given the oral health status is assessed. Considering that DBS CRP and sCRP share only 35% of common variance, further studies should examine their specific validity.
CRIS-Team WoS Importer:2022-01-14

Comparison of dienogest and progesterone effects on uterine contractility in the extracorporeal perfusion model of swine uteri - Oppelt, Patricia; Weber, Meike; Mueller, Andreas; Boosz, Alexander; Hoffmann, Inge; Raffel, Nathalie; Lotz, Laura; Beckmann, Matthias; Dittrich, Ralf (Acta Obstetricia Et Gynecologica Scandinavica, 2018)
INTRODUCTION: Endometriosis is associated with hyperperistalsis and dysperistalsis in the uterus, and it has been shown that progesterone leads to a decrease in uterine contractility. The synthetic gestagen dienogest is often administered in women who are receiving conservative treatment for endometriosis, and it may be the treatment of choice. The present study investigated the effects of dienogest on uterine contractility in comparison with the known inhibitory effect of progesterone. MATERIAL AND METHODS: Eighty swine uteri were examined using an established extracorporeal perfusion model. The uteri were perfused for at least 4 hours with progesterone, dienogest, or a modified Krebs-Ringer solution as the control group, with uterine contractions being measured using an intrauterine microchip catheter. The amplitude and frequency of contractions and the area under the curve (AUC), reflecting overall contractility, were measured at two separate locations (the isthmus and fundus). RESULTS: Progesterone led to a significant decrease in the amplitude of uterine contractions and to reduced overall pressure (AUC) at the isthmus and fundus. Dienogest led to a significant decrease in the amplitude of contractions and overall pressure (AUC) in the area of the isthmus, but the decrease near the fundus was not significant. The frequency of uterine contractions was not influenced by either progesterone or dienogest. CONCLUSIONS: These results confirm the known inhibitory effect of progesterone on uterine contractility (relative to amplitude of contractions and overall contractility), affecting the whole organ. Perfusion of the uterus with dienogest also led to a general decrease in uterine contractility similar to the effect of progesterone.
EVALuna2:209948

Comparison of methods for isolation and quantification of circulating cell-free DNA from patients with endometriosis - Hübner, Hanna; Lubrich, Hannah; Blum, Simon; Antoniadis, Sophia; Lermann, Johannes; Ekici, Arif Bülent; Fasching, Peter; Beckmann, Matthias; Rübner, Matthias; Burghaus, Stefanie (Reproductive Biomedicine Online, 2021)
Research question: Which is the optimal extraction method for isolating and quantifying circulating cell-free DNA (ccfDNA) from patients with endometriosis? Endometriosis is a common benign disease, associated with pain, infertility and reduced quality of life. Endometriosis is also a known risk factor for various cancers. Robust biomarkers for early detection and prediction of prognosis, however, are lacking. CcfDNA is an easy to obtain biomarker associated with prognosis of cancer patients and enables non-invasive analysis of somatic mutations. Recently, elevated levels of ccfDNA were detected in patients with endometriosis. Design: Two different ccfDNA extraction methods were compared: Maxwell RSC ccfDNA plasma kit (Maxwell) and QiAamp minElute ccfDNA mini kit (QIAamp). The ccfDNA and circulating mitochondrial DNA (mtDNA) quantities from 34 patients diagnosed with endometriosis were analysed. Fluorometric measurement and quantitative reverse transcription polymerase chain reaction (qRT-PCR) of short and long ALU and mtDNA fragments were used to quantiy ccfDNA. Results: The yield of ccfDNA isolated with the Maxwell method was significantly higher compared with the QIAamp method (P < 0.0001). Integrity of ccfDNA was significantly higher in the QIAamp isolate (P < 0.0001). Recovered mtDNA was not significantly different between both extraction methods used. Conclusions: The choice of extraction method can significantly influence the ccfDNA output and integrity. Both methods, however, enabled isolation of sufficient ccfDNA for further downstream applications. With this approach, isolation of ccfDNA could enable the non-invasive detection and analysis of somatic mutation within endometriosis tissue.
CRIS-Team Scopus Importer:2021-09-10
Keywords: CcfDNA; Circulating cell-free DNA; Endometriosis; Mitochondrial DNA; Plasma; Quantification

Comparison of Obstetric Efficacy and Safety of the Kiwi OmniCup with Conventional Vacuum Extraction - Siggelkow, W.; Schwarz, N.; Beckmann, Matthias; Kehl, Sven; Faschingbauer, Florian; Schild, R. L. (Geburtshilfe und Frauenheilkunde, 2014)
Purpose: The aim of the present study was to compare the safety and efficacy of the Kiwi OmniCup system with conventional vacuum delivery. Methods: A retrospective study of operative vaginal deliveries was done for 4682 births. The procedures included 217 operative vaginal deliveries (4.6 %), 79 of which were done using conventional vacuum extraction (37 %) and 138 using the Kiwi system (63 %). Results: Use of the Kiwi system was associated with a significant reduction in episiotomies (61 vs. 76 % in the control group; p < 0.05). The rates of successful completion of birth were comparable for the two systems (94 % with the Kiwi system and 99 % with conventional vacuum delivery). Cup detachment occurred significantly more often in the Kiwi group (p < 0.005), requiring a change to a different method of birth significantly more often. It was necessary to change the procedure significantly more often from the mid-pelvis (p < 0.05). The incidence of maternal and foetal injuries was similar for the two systems. Conclusions: With regard to obstetric efficacy and safety and foetal and maternal injuries, the Kiwi system is an acceptable alternative to the conventional vacuum cup. The advantages of the Kiwi system are its significantly lower episiotomy rate and its ease and rapidity of use.
EVALuna2:17446

Comparison of oocyte quality in IVF/ICSI cycles between patients with histologically proven endometriosis and patients where endometriosis has been excluded by laparoscopy - Dittrich, Ralf; Hoffmann, Inge; Beckmann, Matthias; Lotz, Laura (2017)
EVALuna2:36132

Comparison of preoperative and postoperative sexual function in patients with deeply infiltrating endometriosis with and without bowel resection - Lermann, Johannes; Topal, Nalan; Renner, Stefan P.; Beckmann, Matthias; Burghaus, Stefanie; Adler, Werner; Heindl, Felix (European Journal of Obstetrics Gynecology and Reproductive Biology, 2019)
Objective: To analyze preoperative and postoperative sexual function following surgery for deeply infiltrating endometriosis (DIE)with and without bowel involvement. Study design: Patients with DIE who underwent surgery between 2001 and 2011 with segmental bowel resection (WB)or without segmental bowel resection (WOB)were surveyed using the German version of the Massachusetts General Hospital Sexual Functioning Questionnaire (KFSP). Responses were given on a six-point scale for the items sexual interest, sexual arousal, orgasm, lubrication, and general sexual satisfaction. As there are no cut-off values for the existence of sexual function disorders, a control group with no history of endometriosis was evaluated. Differences between the preoperative and postoperative results, as well as between WB, WOB, and a control group, were compared using the Wilcoxon test, Mann–Whitney U test, and Fisher's exact test. Results: Eighty-nine patients without bowel resection (mean age 34.3 years; mean follow-up 63.2 months), 87 patients with bowel resection (mean age 37.7 years; mean follow-up 69.6 months), and 100 control patients aged 21–58 years (mean age 35.0 years)were evaluated. Preoperatively, both treatment groups had significantly poorer scores in all categories in comparison with the control group. The WOB group improved significantly in all categories postoperatively, with no further significant differences from the control group. No significant postoperative improvement was observed in the WB group, and the group had significantly poorer scores in comparison with the control group. The number of previous operations is associated with significantly poorer postoperative KFSP results. Sterility and age > 40 years are associated with significantly less improvement in the KFSP, although with lower initial values. Conclusions: Patients with DIE with or without bowel involvement have significantly impaired sexual function preoperatively. Complete resection of endometriosis in the WOB group was able to improve sexual function, as the women had sexual scores similar to those in the healthy control group postoperatively. Possible explanations for the lack of postoperative improvement of sexual function after segmental bowel resection include the type of surgery carried out, or injury to the affected nerves resulting from the endometriosis.
CRIS-Team Scopus Importer:2019-06-18
Keywords: Deeply infiltrating endometriosis; Lubrication; Massachusetts General Hospital Sexual Functioning Questionnaire; Rectovaginal septum; Sexual function; Sexual satisfaction

Comparison of reoperation rates, perioperative outcomes in women with endometrial cancer when the standard of care shifts from open surgery to laparoscopy - Boosz, Alexander; Häberle, Lothar; Renner, Stefan; Thiel, Falk; Mehlhorn, Grit; Beckmann, Matthias; Mueller, Andreas (Archives of Gynecology and Obstetrics, 2014)
To analyze reoperation rates and perioperative outcomes after long-term follow-up of two surgical approaches in the treatment of endometrial cancer when the standard of care shifts from open surgery to laparoscopy at a university hospital.In this retrospective monocenter study a total of 267 patients with endometrial cancer were included; 107 women underwent laparoscopy and 160 laparotomy. All of the patients received total hysterectomy, bilateral salpingo-oophorectomy, and pelvic and para-aortic lymphadenectomy, depending on individual pathological features (e.g. high risk for positive lymph nodes) and the expertise of the surgeon.Repeat surgery was needed significantly more often in the laparotomy group in comparison with the laparoscopy group (11.9 vs. 0.9 %, respectively; P < 0.001). Hospital stays were longer in the laparotomy group in comparison with laparoscopy (16.2 vs. 9.5 days; P < 0.000001). Postoperative complications were significantly more frequent in the laparotomy group in comparison with laparoscopy (25.0 vs. 10.3 %; P < 0.01). Operating times and preoperative and postoperative hemoglobin differences were similar in the two groups (193.9 vs. 190.6 min, 2.0 vs. 1.8 g/dl). Intraoperative complication rates were similar in the two groups (3.8 vs. 5.6 %).Laparoscopy is a safe alternative to laparotomy for low risk endometrial cancer patients and offers markedly improved perioperative outcomes with a lower reoperation rate and fewer postoperative complications when the standard of care shifts from open surgery to laparoscopy in a university hospital.
EVALuna2:17458

Comparison of Sonography versus Digital Breast Tomosynthesis to Locate Intramammary Marker Clips - Schulz-Wendtland, Rüdiger; Dankerl, Peter; Dilbat, G.; Bani, Mayada; Fasching, Peter; Heusinger, K.; Lux, Michael P.; Löhberg, Christian; Jud, Sebastian; Rauh, C.; Bayer, C. M.; Beckmann, Matthias; et al. (Geburtshilfe und Frauenheilkunde, 2015)
Introduction: This study aimed to compare the accuracy of sonography versus digital breast tomosynthesis to locate intramammary marker clips placed under ultrasound guidance. Patients and Methods: Fifty patients with suspicion of breast cancer (lesion diameter less than 2 cm [cT1]) had ultrasound-guided core needle biopsy with placement of a marker clip in the center of the tumor. Intramammary marker clips were subsequently located with both sonography and digital breast tomosynthesis. Results: Sonography detected no dislocation of intrammammary marker clips in 42 of 50 patients (84 %); dislocation was reported in 8 patients (16 %) with a maximum dislocation of 7 mm along the x-, y- or z-axis. Digital breast tomosynthesis showed accurate placement without dislocation of the intramammary marker clip in 48 patients (96 %); 2 patients (4 %) had a maximum clip dislocation of 3 mm along the x-, y- or z-axis (p < 0.05). Conclusion: The use of digital breast tomosynthesis could improve the accuracy when locating intramammary marker clips compared to sonography and could, in future, be used to complement or even completely replace sonography.
EVALuna2:6724

Comparison of Whole Ovary Cryotreatments for Fertility Preservation - Lotz, Laura; Hauenstein, Tanja; Nichols-Burns, S. M.; Strissel, Pamela; Hoffmann, I.; Findeklee, S.; Dittrich, Ralf; Beckmann, Matthias; Oppelt, Patricia (Reproduction in Domestic Animals, 2015)
The goal of this study was to compare a traditional slow-freeze method (TF) with an open unidirectional slow freeze cooling system (UF) for whole ovary cryopreservation. Therefore, whole pig ovaries were randomly assigned to (A) fresh control, (B) traditional slow freeze (TF) or (C) unidirectional slow freeze (UF). Ovaries were perfused with 10% DMSO in Krebs-Ringer. For TF, whole ovaries were placed in specimen jars containing 10% DMSO and placed into a specialized container for freezing filled with propan-2-ol. For UF, whole ovaries were placed within a specially designed container containing 10% DMSO and transferred to a specialized freezing machine (CTE 920). Histological evaluation demonstrated intact morphology of follicles in all groups; however, an overall decrease of follicle numbers in TF (46%) and UF (50%) compared to fresh control. Live/dead assay indicated significantly lower populations of live cells in both TF (60%) and UF (58%) compared to fresh tissue (74%). TUNEL assay confirmed a difference in percentage of apoptotic follicles between fresh and TF, but there was no significant difference between fresh and UF. To improve the structural and functional integrity of whole ovaries, further investigation, especially into directional freezing, is needed. Whole ovary cryopreservation could provide opportunities for women facing fertility loss due to chemo- or radiotherapy treatment.
EVALuna2:17545

Complementary and alternative medicine and musculoskeletal pain in the first year of adjuvant aromatase inhibitor treatment in early breast cancer patients - Hack, Caroline; Häberle, Lothar; Brucker, S. Y.; Janni, W.; Volz, B.; Löhberg, Christian; Hartkopf, A. D.; Walter, C. B.; Baake, G.; Fridman, A.; Malter, W.; Wuerstlein, R.; et al. (BREAST, 2020)
Background: Patients with breast cancer (BC) show strong interest in complementary and alternative medicine (CAM), particularly for adverse effects of adjuvant endocrine treatment — e.g., with letrozole. Letrozole often induces myalgia/limb pain and arthralgia, with potential noncompliance and treatment termination. This analysis investigated whether CAM before aromatase inhibitor (AI) therapy is associated with pain development and the intensity of AI-induced musculoskeletal syndrome (AIMSS) during the first year of treatment. Patients and methods: The multicenter phase IV PreFace study evaluated letrozole therapy in postmenopausal, hormone receptor–positive patients with early BC. Patients were asked about CAM use before, 6 months after, and 12 months after treatment started. They recorded pain every month for 1 year in a diary including questions about pain and numeric pain rating scales. Data were analyzed for patients who provided pain information for all time points. Results: Of 1396 patients included, 901 (64.5%) had used CAM before AI treatment. Throughout the observation period, patients with CAM before AI treatment had higher pain values, for both myalgia/limb pain and arthralgia, than non-users. Pain increased significantly in both groups over time, with the largest increase during the first 6 months. No significant difference of pain increase was noted regarding CAM use. Conclusions: CAM use does not prevent or improve the development of AIMSS. Pain intensity was generally greater in the CAM group. Therefore, because of the risk of non-compliance and treatment discontinuation due to the development of higher pain levels, special attention must be paid to patient education and aftercare in these patients.
CRIS-Team Scopus Importer:2020-01-31
Keywords: Aromatase inhibitors; Arthralgia; Breast cancer; Complementary and alternative medicine; Endocrine therapy/treatment; Integrative medicine; Letrozole; Myalgia

Complementary and alternative medicine (CAM) in women with endometriosis - Adamietz, Alexandra; Boosz, Alexander; Mueller, Andreas; Hornung, Daniela; Trunk, Katharina; Beckmann, Matthias; Dittrich, Ralf; Hack, Carolin (European Journal of Obstetrics Gynecology and Reproductive Biology, 2021)
Objective: This study aimed to provide an overview of the extent to which women with endometriosis are informed about, interested in, and make use of CAM, and to evaluate which of the methods are most often applied. Study Design: A retrospective, two-center cohort study was conducted using a validated questionnaire among women with laparoscopically confirmed endometriosis at two urban teaching hospitals, certified as endometriosis centres. Results: A total of 592 patients were included in the study and received the questionnaire; 114 (19.3 %) were included in the data analysis. Most of the women were not receiving hormone therapy at the time of the study (n = 60, 52.6 %). Most (n = 75, 65.8 %) were interested in CAM, but only a minority (n = 12, 10.5 %) had detailed knowledge about it. A total of 81 patients (71.1 %) had used at least one CAM method for disease management; the five most frequently used CAM methods were exercise (n = 55, 48.2 %), vitamins (n = 40, 35.1 %), yoga (n = 38, 33.3 %), homeopathy (n = 32, 28.1 %), and trace elements (n = 27, 23.7 %). Conclusions: In our study population, women with endometriosis are strongly interested in using CAM, but have only limited information about it. Nevertheless, a majority of the patients had used at least one CAM method to relieve symptoms associated with the disease and the most often used was exercise.
CRIS-Team Scopus Importer:2021-05-21
Keywords: CAM; Complementary and alternative medicine; Endometriosis

Comprehensive characterization of endometriosis patients and disease patterns in a large clinical cohort - Blum, Simon; Fasching, Peter; Hildebrandt, Thomas; Lermann, Johannes; Heindl, Felix; Born, Tilman; Lubrich, Hannah; Antoniadis, Sophia; Becker, Karina; Fahlbusch, Christine; Heusinger, Katharina; Burghaus, Stefanie; et al. (Archives of Gynecology and Obstetrics, 2021)
Purpose In many diseases, it is possible to classify a heterogeneous group into subgroups relative to tumor biology, genetic variations, or clinical and pathological features. No such classification is available for endometriosis. In our retrospective case-case analysis we defined subgroups of endometriosis patients relative to the type and location of the endometriosis lesion and relative to basic patient characteristics. Methods From June 2013 to July 2017, a total of 1576 patients with endometriosis diagnosed at surgery were included in this study. The patients' history and clinical data were documented using a web-based remote data entry system. To build subgroups, all possible combinations of endometriosis locations/types (peritoneal; ovarian endometriosis; deeply infiltrating endometriosis; adenomyosis) were used. Due to the variation in group sizes, they were combined into five substantial larger groups. Results Age, pregnancy rate, and live birth rate were identified as characteristics that significantly differed between the five patient groups that were defined. No significant differences were noted in relation to body mass index, length of menstrual cycle, age at menarche, reason for presentation, or educational level. Conclusion This study describes basic patient characteristics in relation to common clinical subgroups in a large clinical cohort of endometriosis patients. Epidemiological information about different clinical groups may be helpful in identifying groups with specific clinical courses, potentially suggesting novel approaches to early detection and to surgical and systemic treatment.
CRIS-Team WoS Importer:2021-09-10

Comprehensive genetic assessment of the ESR1 locus identifies a risk region for endometrial cancer - O'Mara, Tracy A.; Glubb, Dylan M.; Painter, Jodie N.; Cheng, Timothy; Dennis, Joe; Attia, John; Holliday, Elizabeth G.; Mcevoy, Mark; Scott, Rodney J.; Ashton, Katie; Proietto, Tony; Otton, Geoffrey; et al. (Endocrine-Related Cancer, 2015)
Excessive exposure to estrogen is a well-established risk factor for endometrial cancer (EC), particularly for cancers of endometrioid histology. The physiological function of estrogen is primarily mediated by estrogen receptor alpha, encoded by ESR1. Consequently, several studies have investigated whether variation at the ESR1 locus is associated with risk of EC, with conflicting results. We performed comprehensive fine-mapping analyses of 3633 genotyped and imputed single nucleotide polymorphisms (SNPs) in 6607 EC cases and 37 925 controls. There was evidence of an EC risk signal located at a potential alternative promoter of the ESR1 gene (lead SNP rs79575945, P=1.86×10(-5)), which was stronger for cancers of endometrioid subtype (P=3.76×10(-6)). Bioinformatic analysis suggests that this risk signal is in a functionally important region targeting ESR1, and eQTL analysis found that rs79575945 was associated with expression of SYNE1, a neighbouring gene. In summary, we have identified a single EC risk signal located at ESR1, at study-wide significance. Given SNPs located at this locus have been associated with risk for breast cancer, also a hormonally driven cancer, this study adds weight to the rationale for performing informed candidate fine-scale genetic studies across cancer types.
EVALuna2:9261

Comprehensive visualization of paresthesia in breast cancer survivors - Jud, Sebastian; Hatko, Reinhard; Maihoefner, Christian; Bani, Mayada; Schrauder, Michael G.; Lux, Michael P.; Beckmann, Matthias; Bani, Gassan; Eder, Irina; Fasching, Peter; Löhberg, Christian; Rauh, Claudia; et al. (Archives of Gynecology and Obstetrics, 2014)
As breast cancer survivors are benefiting increasingly from advanced forms of therapy, the side effects of locoregional treatment in the adjuvant setting are becoming more and more important. This article presents a new method of assessing the spatial distribution of paresthesia in breast cancer survivors after different locoregional treatments.A structured questionnaire assessing paresthesia, with body pictograms for marking paresthesia areas, was completed by 343 breast cancer survivors. The image information was digitized, generating gray-scale summation images with numbers from 0, indicating black (100 % of the patients had paresthesia), to 255, indicating white (none had paresthesia). The resulting map visualization showed the locations of paresthesia on body pictograms. The group included patients who had undergone breast-conserving surgery (BCS) and mastectomy, and also patients who had received percutaneous and interstitial radiation.A total of 56.5 % of the patients stated that they had paresthesia. The paresthesia areas were distributed within the range suggested by clinical experience. Most patients stated that they had paresthesia in the upper outer quadrant and axilla. Patients who had undergone mastectomy or percutaneous radiotherapy appeared to have more paresthesia on some areas of the body surface. Patients who had undergone mastectomy indicated larger areas of paresthesia than those with BCS-4,066 pixels (px) vs. 2,275 px. Radiotherapy did not appear to influence the spatial distribution of paresthesia.Paresthesia is a common symptom after breast cancer treatment. This paper describes a new method of assessing this side effect to improve and individualize treatment for it in the future.
EVALuna2:17450

Computerized patient identification for the EMBRACA clinical trial using real-time data from the PRAEGNANT network for metastatic breast cancer patients - Hein, Alexander; Gaß, Paul; Walter, Christina Barbara; Taran, Florin-Andrei; Hartkopf, Andreas; Overkamp, Friedrich; Kolberg, Hans-Christian; Hadji, Peyman; Tesch, Hans; Ettl, Johannes; Wuerstlein, Rachel; Lounsbury, Debra; et al. (Breast Cancer Research and Treatment, 2016)
EVALuna2:154
Keywords: BRCA1; BRCA2; Breast cancer; Clinical trial eligibility; PARP inhibitors; Talazoparib

Concentrations of N epsilon-Carboxymethyllysine in Human Breast Milk, Infant Formulas, and Urine of Infants - Dittrich, Ralf; Hoffmann, Inge; Stahl, Peter; Müller, Andreas; Beckmann, Matthias; Pischetsrieder, Monika (Journal of Agricultural and Food Chemistry, 2006)
Maillard products, such as Nε-carboxymethyllysine (CML), are readily formed during the manufacturing of infant formulas. Little has been known, however, about the presence of CML in human breast milk and about the uptake of CML by infants. In this study, CML was measured in the serum and breast milk of 32 healthy mothers by ELISA. CML concentrations in breast milk (137 ± 82.7 ng/mL) were significantly lower than in the serum (399 ± 67.8 ng/mL, p < 0.001) and on average 35-fold lower than in infant formulas (4754 ± 4299.5 ng/mL). CML was also measured in the urine of 21 infants, which were fed with breast milk or formulas. Although there was a tendency toward higher urinary CML excretion in infants fed with hypoallergenic formulas compared to breast-fed ones, the differences were not significant. Neonates that were delivered by vaginal birth had significantly higher concentrations of CML compared to those delivered by caesarean section (1306 ± 653 vs 601 ± 220 ng/mL, p = 0.012). It is conclued that CML passes from the serum into the breast milk, but the levels are by far lower than in infant formulas. In very young neonates (≤3 days), the mode of delivery has a greater influence on urinary CML excretion than the nutrition. © 2006 American Chemical Society.
UnivIS-Import:2015-04-14:Pub.2006.nat.dchph.llmch.concen
Keywords: Advanced glycation end-products; Breast milk; Infant formulas; Maillard products; N; Newborn; Urine

Concept paper on the technique of cryopreservation, removal and transplantation of ovarian tissue for fertility preservation - Beckmann, Matthias; Lotz, Laura; Toth, Bettina; Baston-Buest, Dunja Maria; Fehm, Tanja; Frambach, Torsten; Germeyer, Ariane; Goeckenjan, Maren; Haeberlin, Felix; Henes, Melanie; Hirchenhain, Jens; Huebner, Stephanie; et al. (Geburtshilfe und Frauenheilkunde, 2019)
The cryopreservation of ovarian tissue with subsequent transplantation of the tissue represents an established method of fertility protection for female patients who have to undergo gonadotoxic therapy. The procedure can be performed at any point in the cycle and thus generally does not lead to any delay in oncological therapy. With the aid of this procedure, more than 130 births to date worldwide have been able to be recorded. The birth rate is currently approximately 30% and it can be assumed that this will increase through the further optimisation of the cryopreservation and surgical technique. The concept paper presented here is intended to provide guidance for managing cryopreservation and transplantation of ovarian tissue to German-speaking reproductive medicine centres.
CRIS-Team Scopus Importer:2019-05-14
Keywords: Cryopreservation; Fertility protection; FertiPROTEKT; Ovarian tissue; Transplantation

Concerning Dediu M, Zielinski A: A Proposal to Redefine Pathologic Complete Remission as Endpoint following Neoadjuvant Chemotherapy in Early Breast Cancer. Breast Care 2019; Doi 10.1159/000500620 - Untch, Michael; Loibl, Sibylle; Fasching, Peter (Breast Care, 2019)
CRIS-Team Scopus Importer:2019-06-18

Concordance Rate of Colposcopy in Detecting Cervical Intraepithelial Lesions - Stübs, Frederik; Dietl, Anna; Behrens, Annika; Adler, Werner; Geppert, Carol-Immanuel; Hartmann, Arndt; Knöll, Antje; Beckmann, Matthias; Mehlhorn, Grit; Schulmeyer, Carla; Gaß, Paul; Koch, Martin C. (Diagnostics, 2022)
Background: The purpose of this research is to estimate the rate of concordance, sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of colposcopy for high-grade squamous lesions and carcinomas (HSIL+). Methods: We conducted a retrospective study of colposcopies performed in the certified Dysplasia Unit in Erlangen between January 2015 and May 2022 (7.5 years). The colposcopic findings were correlated with biopsies obtained during examinations or surgery. Cases without histology were excluded. The primary outcome was the rate of concordance between the colposcopic and histological findings in relation to the type of transformation zone (TZ), examiner's level of experience and age of the patients. Results: A total of 4778 colposcopies in 4001 women were analyzed. The rates of concordance for CIN I/LSIL, CIN II/HSIL, CIN III/HSIL, and carcinoma were 43.4%, 59.5%, 78.5%, and 53.9%, respectively. The rate of concordance was lowest for TZ3 and highest for colposcopists with more than 10 years' experience. Conclusions: Colposcopy is an important, feasible, and effective method. Careful work-up needs to be performed for women with TZ3 who are over 35 years old, as they are at the highest risk of being misdiagnosed. The highest concordance for detecting HSIL+ was seen for colposcopists with >10 years' experience.
CRIS-Team WoS Importer:2022-11-11

Concordance rate of vulvoscopic findings in detecting early vulvar neoplasia - Stuebs, Frederik A.; Mehlhorn, Grit; Gaß, Paul; Schulmeyer, Carla; Adler, Werner; Strehl, Johanna; Hartmann, Arndt; Beckmann, Matthias; Renner, Stefan; Koch, Martin (Gynecologic Oncology, 2020)
Purpose: Colposcopy-guided punch biopsy is a cornerstone method for diagnosing vulvar diseases. The aim of this study was to evaluate the concordance rate of clinical findings in vulvar diseases during examinations, in comparison with colposcopy-directed punch biopsy. We also developed a new classification to simplify the categorization of vulvoscopic findings. Methods: The concordance rate of the clinical findings was compared with the final histology results from punch biopsies. The data were collected between January 2014 and May 2017 at the Erlangen University Hospital. Results: A total of 482 colposcopy-directed punch biopsies of the vulva were obtained in 420 women. The overall concordance rate of the clinical findings in comparison with the histological vulvar punch-biopsy findings was 53.9% for all entities — benign lesions, lichen, low- and high-grade squamous intraepithelial lesions (LSIL/HSILs), and vulvar carcinoma. The concordance rate for detecting LSILs was 64.3% (45/70). The concordance rate for detecting HSILs was 62.3% and for Vulvar carcinoma 65.2%. Conclusions: Punch biopsy of suspicious lesions continues to be a cornerstone in diagnosing HSILs and carcinoma of the vulva. Careful work-up of the vulva is recommended when patients have symptoms such as pruritus or pain. The new classification is more specific for diagnosing lesions in the vulva.
CRIS-Team Scopus Importer:2020-03-06
Keywords: Colposcopy-directed punch biopsy; High-grade squamous intraepithelial lesion (HSIL); Vulvar cancer; Vulvar intraepithelial neoplasia (VIN)

Concurrent RB1 Loss and BRCA Deficiency Predicts Enhanced Immunologic Response and Long-term Survival in Tubo-ovarian High-grade Serous Carcinoma - Saner, Flurina A.M.; Takahashi, Kazuaki; Budden, Timothy; Pandey, Ahwan; Ariyaratne, Dinuka; Zwimpfer, Tibor A.; Meagher, Nicola S.; Fereday, Sian; Twomey, Laura; Pishas, Kathleen I.; Hoang, Therese; Bolithon, Adelyn; et al. (Clinical Cancer Research, 2024)
PURPOSE: The purpose of this study was to evaluate RB1 expression and survival across ovarian carcinoma histotypes and how co-occurrence of BRCA1 or BRCA2 (BRCA) alterations and RB1 loss influences survival in tubo-ovarian high-grade serous carcinoma (HGSC). EXPERIMENTAL DESIGN: RB1 protein expression was classified by immunohistochemistry in ovarian carcinomas of 7,436 patients from the Ovarian Tumor Tissue Analysis consortium. We examined RB1 expression and germline BRCA status in a subset of 1,134 HGSC, and related genotype to overall survival (OS), tumor-infiltrating CD8+ lymphocytes, and transcriptomic subtypes. Using CRISPR-Cas9, we deleted RB1 in HGSC cells with and without BRCA1 alterations to model co-loss with treatment response. We performed whole-genome and transcriptome data analyses on 126 patients with primary HGSC to characterize tumors with concurrent BRCA deficiency and RB1 loss. RESULTS: RB1 loss was associated with longer OS in HGSC but with poorer prognosis in endometrioid ovarian carcinoma. Patients with HGSC harboring both RB1 loss and pathogenic germline BRCA variants had superior OS compared with patients with either alteration alone, and their median OS was three times longer than those without pathogenic BRCA variants and retained RB1 expression (9.3 vs. 3.1 years). Enhanced sensitivity to cisplatin and paclitaxel was seen in BRCA1-altered cells with RB1 knockout. Combined RB1 loss and BRCA deficiency correlated with transcriptional markers of enhanced IFN response, cell-cycle deregulation, and reduced epithelial-mesenchymal transition. CD8+ lymphocytes were most prevalent in BRCA-deficient HGSC with co-loss of RB1. CONCLUSIONS: Co-occurrence of RB1 loss and BRCA deficiency was associated with exceptionally long survival in patients with HGSC, potentially due to better treatment response and immune stimulation.
CRIS-Team Scopus Importer:2024-08-23

Conditional progression-free survival in patients with metastatic hormone receptor-positive, human epidermal growth factor receptor 2-negative breast cancer treated with first-line ribociclib and endocrine therapy: real-world data from the RIBANNA study - Decker, T.; Brucker, C.; Engel, A.; Fasching, Peter; Göhler, T.; Jackisch, C.; Janssen, J.; Köhler, A.; Lüdtke-Heckenkamp, K.; Lüftner, D.; Marmé, F.; van Mackelenbergh, M.; et al. (ESMO Open, 2025)
Background: Progression-free survival (PFS) for patients with metastatic hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2−) breast cancer significantly improved with cyclin-dependent kinase 4/6 inhibitors as part of first-line treatment. No data is available for these patients on how the risk of progression evolves. Therefore, we analyzed conditional PFS (cPFS), which reflects patient prognosis after initial management, that is, the probability of remaining free from progression in those who have already survived without progression for a given period. Patients and methods: We analyzed PFS and cPFS for patients free from progression after 12, 24, and 36 months (reference time points) treated with ribociclib and endocrine therapy (ET) as first-line treatment for advanced HR+, HER2− breast cancer (aBC) within the RIBANNA noninterventional study (NCT06311383). Relevant subgroups with established prognostic factors were additionally examined. Results: Compared with the median PFS of 35 months (95% confidence interval 32.3-38.4 months) in the overall population, the median cPFS was higher for all reference points: cPFS of 40.5 months (95% confidence interval 35.0-45.5 months) for patients who were progression-free 12 months, cPFS of 53.6 months (95% confidence interval 42.7-not reached months) for 24 months reference point, whereas for the 36 months reference point, the median cPFS was not reached. After patients had reached 2-year disease control, the initial presence of liver metastases or grade 3 disease no longer qualified as poor prognostic factors; internal organ metastases (central nervous system, liver, and lungs) showed a diminishing prognostic impact over time. A short treatment-free interval remained a relevant prognostic factor. Conclusion: For the first time, increasing cPFS was demonstrated in patients treated with ribociclib and ET. Such information is highly relevant and reassuring for patients with HR+, HER2− aBC, and could be used to aid patient counseling and treatment decision-making, including possible de-escalation strategies. It is also a starting point for identifying dynamic prognostic factors related to long-term survival.
CRIS-Team Scopus Importer:2025-05-23
Keywords: advanced breast cancer; conditional progression-free survival; conditional survival; metastatic breast cancer; RIBANNA; ribociclib

Considerations on the Improved Integration of Medical Guidelines into Routine Clinical Practice - a Review and Concept Proposal - Beckmann, Matthias; Schlieter, H.; Richter, P.; Wesselmann, S. (Geburtshilfe und Frauenheilkunde, 2016)
Medical guidelines have become established as the standard for the comprehensive synopsis of all available information (scientific trials, expert opinion) on diagnosis and treatment recommendations. The transfer of guidelines to clinical practice and subsequent monitoring has however proven difficult. In particular the potential interaction between guideline developers and guideline users has not been fully utilised. This review article analyses the status quo and existing methodological and technical information solutions supporting the guideline life cycle. It is shown that there are numerous innovative developments that in isolation do not provide comprehensive support. The vision of the "Living Guidelines 2.0" is therefore presented. This outlines the merging of guideline development and implementation on the basis of clinical pathways and guideline-based quality control, and building on this, the generation of information for guideline development and research.
EVALuna2:32985

Consortium analysis of gene and gene-folate interactions in purine and pyrimidine metabolism pathways with ovarian carcinoma risk - Kelemen, Linda E.; Terry, Kathryn L.; Goodman, Marc T.; Webb, Penelope M.; Bandera, Elisa V.; Mcguire, Valerie; Rossing, Mary Anne; Wang, Qinggang; Dicks, Ed; Tyrer, Jonathan P.; Song, Honglin; Kupryjanczyk, Jolanta; et al. (Molecular Nutrition & Food Research, 2014)
We reevaluated previously reported associations between variants in pathways of one-carbon (1-C) (folate) transfer genes and ovarian carcinoma (OC) risk, and in related pathways of purine and pyrimidine metabolism, and assessed interactions with folate intake.Odds ratios (OR) for 446 genetic variants were estimated among 13,410 OC cases and 22,635 controls, and among 2281 cases and 3444 controls with folate information. Following multiple testing correction, the most significant main effect associations were for dihydropyrimidine dehydrogenase (DPYD) variants rs11587873 (OR = 0.92; p = 6 × 10(-5)) and rs828054 (OR = 1.06; p = 1 × 10(-4)). Thirteen variants in the pyrimidine metabolism genes, DPYD, DPYS, PPAT, and TYMS, also interacted significantly with folate in a multivariant analysis (corrected p = 9.9 × 10(-6)) but collectively explained only 0.2% of OC risk. Although no other associations were significant after multiple testing correction, variants in SHMT1 in 1-C transfer, previously reported with OC, suggested lower risk at higher folate (p(interaction) = 0.03-0.006).Variation in pyrimidine metabolism genes, particularly DPYD, which was previously reported to be associated with OC, may influence risk; however, stratification by folate intake is unlikely to modify disease risk appreciably in these women. SHMT1 SNP-by-folate interactions are plausible but require further validation. Polymorphisms in selected genes in purine metabolism were not associated with OC.
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Co-observation of germline pathogenic variants in breast cancer predisposition genes: Results from analysis of the BRIDGES sequencing dataset - Davidson, Aimee L.; Michailidou, Kyriaki; Parsons, Michael T.; Fortuno, Cristina; Bolla, Manjeet K.; Wang, Qin; Dennis, Joe; Naven, Marc; Abubakar, Mustapha; Ahearn, Thomas U.; Alonso, M. Rosario; Andrulis, Irene L.; et al. (American Journal of Human Genetics, 2024)
Co-observation of a gene variant with a pathogenic variant in another gene that explains the disease presentation has been designated as evidence against pathogenicity for commonly used variant classification guidelines. Multiple variant curation expert panels have specified, from consensus opinion, that this evidence type is not applicable for the classification of breast cancer predisposition gene variants. Statistical analysis of sequence data for 55,815 individuals diagnosed with breast cancer from the BRIDGES sequencing project was undertaken to formally assess the utility of co-observation data for germline variant classification. Our analysis included expected loss-of-function variants in 11 breast cancer predisposition genes and pathogenic missense variants in BRCA1, BRCA2, and TP53. We assessed whether co-observation of pathogenic variants in two different genes occurred more or less often than expected under the assumption of independence. Co-observation of pathogenic variants in each of BRCA1, BRCA2, and PALB2 with the remaining genes was less frequent than expected. This evidence for depletion remained after adjustment for age at diagnosis, study design (familial versus population-based), and country. Co-observation of a variant of uncertain significance in BRCA1, BRCA2, or PALB2 with a pathogenic variant in another breast cancer gene equated to supporting evidence against pathogenicity following criterion strength assignment based on the likelihood ratio and showed utility in reclassification of missense BRCA1 and BRCA2 variants identified in BRIDGES. Our approach has applicability for assessing the value of co-observation as a predictor of variant pathogenicity in other clinical contexts, including for gene-specific guidelines developed by ClinGen Variant Curation Expert Panels.
CRIS-Team Scopus Importer:2024-08-30
Keywords: ACMG/AMP; BP5; breast cancer; co-observation; genetics; sequencing data; variant classification

Copy Number Variants Are Ovarian Cancer Risk Alleles at Known and Novel Risk Loci - Devries, Amber A.; Dennis, Joe; Tyrer, Jonathan P.; Peng, Pei-Chen; Coetzee, Simon G.; Reyes, Alberto L.; Plummer, Jasmine T.; Davis, Brian D.; Chen, Stephanie S.; Dezem, Felipe Segato; Aben, Katja K. H.; Anton-Culver, Hoda; et al. (Journal of the National Cancer Institute, 2022)
Background Known risk alleles for epithelial ovarian cancer (EOC) account for approximately 40% of the heritability for EOC. Copy number variants (CNVs) have not been investigated as EOC risk alleles in a large population cohort. Methods Single nucleotide polymorphism array data from 13 071 EOC cases and 17 306 controls of White European ancestry were used to identify CNVs associated with EOC risk using a rare admixture maximum likelihood test for gene burden and a by-probe ratio test. We performed enrichment analysis of CNVs at known EOC risk loci and functional biofeatures in ovarian cancer-related cell types. Results We identified statistically significant risk associations with CNVs at known EOC risk genes; BRCA1 (P-EOC = 1.60E-21; OREOC = 8.24), RAD51C (Phigh-grade serous ovarian cancer [HGSOC] = 5.5E-4; odds ratio [OR](HGSOC) = 5.74 del), and BRCA2 (P-HGSOC = 7.0E-4; ORHGSOC = 3.31 deletion). Four suggestive associations (P < .001) were identified for rare CNVs. Risk-associated CNVs were enriched (P < .05) at known EOC risk loci identified by genome-wide association study. Noncoding CNVs were enriched in active promoters and insulators in EOC-related cell types. Conclusions CNVs in BRCA1 have been previously reported in smaller studies, but their observed frequency in this large population-based cohort, along with the CNVs observed at BRCA2 and RAD51C gene loci in EOC cases, suggests that these CNVs are potentially pathogenic and may contribute to the spectrum of disease-causing mutations in these genes. CNVs are likely to occur in a wider set of susceptibility regions, with potential implications for clinical genetic testing and disease prevention.
CRIS-Team WoS Importer:2022-10-21

Correction: Collective forces of tumor spheroids in three-dimensional biopolymer networks. - Mark, Christoph; Grundy, Thomas J.; Strissel, Pamela; Böhringer, David; Grummel, Nadine; Gerum, Richard; Steinwachs, Julian; Hack, Carolin; Beckmann, Matthias; Eckstein, Markus; Strick, Reiner; O'Neill, Geraldine M.; et al. (eLife, 2020)
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Correction: PredictCBC-2.0: a contralateral breast cancer risk prediction model developed and validated in 200,000 patients (Breast Cancer Research, (2022), 24, 1, (69), 10.1186/s13058-022-01567-3) - Giardiello, Daniele; Hooning, Maartje J.; Hauptmann, Michael; Keeman, Renske; Heemskerk-Gerritsen, B. A.M.; Becher, Heiko; Blomqvist, Carl; Bojesen, Stig E.; Bolla, Manjeet K.; Camp, Nicola J.; Czene, Kamila; Devilee, Peter; et al. (BREAST CANCER RES, 2022)
CRIS-Team Scopus Importer:2022-12-02

Correction to: Breast cancer patients' satisfaction with individual therapy goals and treatment in a standardized integrative medicine consultancy service - Hack, Carolin; Antoniadis, Sophia; Hackl, Janina; Langemann, Hanna; Schwitulla, Judith; Fasching, Peter; Beckmann, Matthias; Theuser, Anna-Katharin (Archives of Gynecology and Obstetrics, 2018)
In the original version of this article contained an error in figure 1. It was provided in German.
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Correction to: Comparative assessment of breast volume using a smartphone device versus MRI (Breast Cancer, (2025), 32, 1, (166-176), 10.1007/s12282-024-01647-6) - Behrens, Annika; Hübner, Hanna; Häberle, Lothar; Stamminger, Marc; Zint, Daniel; Heindl, Felix; Emons, Julius; Hack, Carolin; Nabieva, Naiba; Uder, Michael; Wetzl, Matthias; Wunderle, Marius; et al. (Breast Cancer, 2025)
The article ‘Comparative assessment of breast volume using a smartphone device versus MRI’, written by Annika S. Behrens, Hanna Huebner, Lothar Häberle, Marc Stamminger, Daniel Zint, Felix Heindl, Julius Emons, Carolin C. Hack, Naiba Nabieva, Michael Uder, Matthias Wetzl, Marius Wunderle, Matthias W. Beckmann, Peter A. Fasching, Sabine Ohlmeyer, was originally published under exclusive license to The Author(s), under exclusive licence to The Japanese Breast Cancer Society. As a result of the subsequent decision to publish the article under the open access model, the article’s copyright notice was changed on 12 February 2025 to © The Author(s) 2025 and the article is now distributed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The original article has been corrected.
CRIS-Team Scopus Importer:2025-03-21

Correction to: Genetic drivers and cellular selection of female mosaic X chromosome loss (Nature, (2024), 631, 8019, (134-141), 10.1038/s41586-024-07533-7) - Liu, Aoxing; Genovese, Giulio; Zhao, Yajie; Pirinen, Matti; Zekavat, Seyedeh M.; Kentistou, Katherine A.; Yang, Zhiyu; Yu, Kai; Vlasschaert, Caitlyn; Liu, Xiaoxi; Brown, Derek W.; Hudjashov, Georgi; et al. (Nature, 2024)
Correction to: Naturehttps://doi.org/10.1038/s41586-024-07533-7 Published online 12 June 2024 In the version of this article initially published, members of the Breast Cancer Association Consortium did not appear in the full text and have now been added in the HTML and PDF versions of the article.
CRIS-Team Scopus Importer:2025-02-04

Correction to: Introducing multiple-choice questions to promote learning for medical students: effect on exam performance in obstetrics and gynecology (Archives of Gynecology and Obstetrics, (2020), 302, 6, (1401-1406), 10.1007/s00404-020-05758-1) - Jud, Sebastian; Cupisti, Susanne; Frobenius, Wolfgang; Winkler, Andrea; Schultheis, Franziska; Antoniadis, Sophia; Beckmann, Matthias; Heindl, Felix (Archives of Gynecology and Obstetrics, 2021)
A correction to this paper has been published: https://doi.org/10.1007/s00404-021-06112-9.
CRIS-Team Scopus Importer:2021-07-02

Correction to: TGFB-induced factor homeobox 1 (TGIF) expression in breast cancer (BMC Cancer, (2021), 21, 1, (920), 10.1186/s12885-021-08656-0) - Stuerken, Christine; Moebus, Volker; Milde-Langosch, Karin; Schmatloch, Sabine; Fasching, Peter; Rueschoff, Josef; Stickeler, Elmar; Henke, Rolf-Peter; Denkert, Carsten; Hanker, Lars; Schem, Christian; Vladimirova, Valentina; et al. (BMC Cancer, 2021)
CRIS-Team Scopus Importer:2021-09-24

Correction to: Understanding the genetic complexity of puberty timing across the allele frequency spectrum (Nature Genetics, (2024), 56, 7, (1397-1411), 10.1038/s41588-024-01798-4) - Kentistou, Katherine A.; Kaisinger, Lena R.; Stankovic, Stasa; Vaudel, Marc; Mendes de Oliveira, Edson; Messina, Andrea; Walters, Robin G.; Liu, Xiaoxi; Busch, Alexander S.; Helgason, Hannes; Thompson, Deborah J.; Santoni, Federico; et al. (Nature Genetics, 2024)
Correction to: Nature Geneticshttps://doi.org/10.1038/s41588-024-01798-4, published online 1 July 2024. In the version of the article initially published, in Fig. 5c, the trajectory labels now reading T01, T02, T03, T04, T05, T06, T07, T08, T09 and T10 appeared incorrectly as T-01, T-02, T-03, T-04, T-05, T-06, T-07, T-08, T-09 and T-10. The figure has now been amended in the HTML and PDF versions of the article.
CRIS-Team Scopus Importer:2024-11-01

Correlation between referral cytology and in-house colposcopy-guided cytology for detecting early cervical neoplasia - Schulmeyer, Carla; Stübs, Frederik; Gaß, Paul; Renner, Stefan; Hartmann, Arndt; Strehl, Johanna; Mehlhorn, Grit; Geppert, Carol-Immanuel; Adler, Werner; Beckmann, Matthias; Koch, Martin (Archives of Gynecology and Obstetrics, 2019)
Purpose: The current cervical cancer screening program in Germany recommends that the results showing suspected HPV infection should be further examined in specialized colposcopy units. This study aimed to correlate externally documented Pap smear results with in-house colposcopy-guided Pap cytology results and compare colposcopy-guided biopsy and postoperative histopathology results. Methods: Clinical data were analyzed from 3627 examinations in 2844 patients who visited a university certified dysplasia unit from 2014 to 2017; 2212 patients underwent complete assessments, including Pap smear, colposcopy, HPV testing, colposcopy-guided biopsy, and/or surgery. The results were analyzed descriptively. Results: External and in-house Pap results were consistent in 1054 ofthe 2212 patients (47.65%). Referral cytology showed a higher grade than in-house in 456 (20.61%) and a lower grade in 702 (31.74%). Using the histopathological findings as the gold standard, overdiagnosis in the referral cytology was noted in 180 patients (13.19%), underdiagnosis in 263 (19.27%), and concordant findings in 922 (67.55%). For in-house cytology, overdiagnosis was found in 133 patients (10.74%), underdiagnosis in 192 (15.51%), and accurate diagnosis with congruent cytology and histopathology findings in 913 (73.75%). Conclusions: The rate of detection of cervical abnormalities differs significantly depending on whether the examination is performed routinely or in specialized units. Colposcopy-guided Pap smears correlate significantly better with histology than referral cytology results without colposcopic guidance. More severe lesions were also detected more accurately.
CRIS-Team Scopus Importer:2019-12-20
Keywords: Cervical cancer screening; Cervical intraepithelial neoplasia (CIN); Dysplasia; High-grade squamous intraepithelial lesion (HSIL); Low-grade squamous intraepithelial lesion (LSIL); Pap smear; Precancerous lesions of the cervix

Correlation of histological and macroscopic findings in peritoneal endometriosis - Strehl, Johanna; Hackl, Janina; Wachter, David; Klingsiek, Peter; Burghaus, Stefanie; Renner, Stefan; Fasching, Peter; Hartmann, Arndt; Beckmann, Matthias (International Journal of Clinical and Experimental Pathology, 2014)
In the last two decades, a color based concept of disease activity in peritoneal endometriosis has been in use in the clinical context, with red lesions being considered active and black or white lesions being interpreted as less active or dormant.Our aim was to analyze 4 main color categories of peritoneal endometriosis (black, white, red and brown) in one single patient group using histomorphological and immunohistochemical methods.65 endometriosis lesions (30 black, 17 white, 11 brown, 7 red) were resected from 47 premenopausal, nulliparous women which had not received exogenous hormones for at least six months prior to the operation. Specimen workup, histomorphological analysis and immunohistochemical analysis were performed in a standardized manner.The color categories showed a broad overlap in proliferative activity and hormone receptor expression. Differences were found in lesion morphology. Adjacent stromal reaction in particular showed a marked increase from red through brown and black to white lesions. Differences were also seen in gland pattern and gland content.Lesion colors in peritoneal endometriosis seem to be determined by gland content and a varying adjacent stromal reaction and more likely reflect an aging process than different levels of disease activity.
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Correlation of mammographic density and serum calcium levels in patients with primary breast cancer - Hack, Carolin; Stoll, Martin; Jud, Sebastian; Heusinger, Katharina; Adler, Werner; Haeberle, Lothar; Ganslandt, Thomas; Heindl, Felix; Schulz-Wendtland, Rüdiger; Uder, Michael; Beckmann, Matthias; Fasching, Peter; et al. (Cancer Medicine, 2017)
Percentage mammographic breast density (PMD) is one of the most important risk factors for breast cancer (BC). Calcium, vitamin D, bisphosphonates, and denosumab have been considered and partly confirmed as factors potentially influencing the risk of BC. This retrospective observational study investigated the association between serum calcium level and PMD. A total of 982 BC patients identified in the research database at the University Breast Center for Franconia with unilateral BC, calcium and albumin values, and mammogram at the time of first diagnosis were included. PMD was assessed, using a semiautomated method by two readers. Linear regression analyses were conducted to investigate the impact on PMD of the parameters of serum calcium level adjusted for albumin level, and well-known clinical predictors such as age, body mass index (BMI), menopausal status and confounder for serum calcium like season in which the BC was diagnosed. Increased calcium levels were associated with reduced PMD (P = 0.024). Furthermore, PMD was inversely associated with BMI (P < 0.001) and age (P < 0.001). There was also an association between PMD and menopausal status (P < 0.001). The goodness-of-fit of the regression model was moderate. This is the first study assessing the association between serum calcium level and PMD. An inverse association with adjusted serum calcium levels was observed. These findings add to previously published data relating to vitamin D, bisphosphonates, denosumab, and the RANK/RANKL signaling pathway in breast cancer risk and prevention.
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Correlation of RANK and RANKL with mammographic density in primary breast cancer patients - Wunderle, Marius; Heindl, Felix; Behrens, Annika; Häberle, Lothar; Hack, Carolin; Heusinger, Katharina; Hübner, Hanna; Gaß, Paul; Rübner, Matthias; Schulz-Wendtland, Rüdiger; Erber, Ramona; Hartmann, Arndt; et al. (Archives of Gynecology and Obstetrics, 2024)
Purpose: The receptor activator of nuclear factor kappa B (RANK) and its ligand (RANKL) have been shown to promote proliferation of the breast and breast carcinogenesis. The objective of this analysis was to investigate whether tumor-specific RANK and RANKL expression in patients with primary breast cancer is associated with high percentage mammographic density (PMD), which is a known breast cancer risk factor. Methods: Immunohistochemical staining of RANK and RANKL was performed in tissue microarrays (TMAs) from primary breast cancer samples of the Bavarian Breast Cancer Cases and Controls (BBCC) study. For RANK and RANKL expression, histochemical scores (H scores) with a cut-off value of > 0 vs 0 were established. PMD was measured in the contralateral, non-diseased breast. Linear regression models with PMD as outcome were calculated using common predictors of PMD (age at breast cancer diagnosis, body mass index (BMI) and parity) and RANK and RANKL H scores. Additionally, Spearman rank correlations (ρ) between PMD and RANK and RANKL H score were performed. Results: In the final cohort of 412 patients, breast cancer-specific RANK and RANKL expression was not associated with PMD (P = 0.68). There was no correlation between PMD and RANK H score (Spearman’s ρ = 0.01, P = 0.87) or RANKL H score (Spearman’s ρ = 0.04, P = 0.41). RANK expression was highest in triple-negative tumors, followed by HER2-positive, luminal B-like and luminal A-like tumors, while no subtype-specific expression of RANKL was found. Conclusion: Results do not provide evidence for an association of RANK and RANKL expression in primary breast cancer with PMD.
CRIS-Team Scopus Importer:2024-06-14
Keywords: Breast cancer; Immunohistochemistry; Mammographic density; RANK expression; RANKL expression

Correlation of short-term variation and Doppler parameters with adverse perinatal outcome in low-risk fetuses at term - Stumpfe, Florian M.; Kehl, Sven; Pretscher, Jutta; Baier, Friederike; Bayer, Christian M.; Schwenke, Eva; Schneider, Michael; Mayr, Andreas; Schild, Ralf L.; Schmid, Matthias; Beckmann, Matthias; Faschingbauer, Florian (Archives of Gynecology and Obstetrics, 2019)
ObjectiveTo evaluate the association of short-term variation (STV) and Doppler parameters with adverse perinatal outcome in low-risk fetuses at term.MethodsThis was a retrospective study of 1008 appropriate-for-gestational age (AGA) term fetuses. Doppler measurements [umbilical artery (UA), middle cerebral artery (MCA), and cerebroplacental ratio (CPR)] and computerized CTG (cCTG) with STV analysis were performed prior to active labor (4cm cervical dilatation) within 72h of delivery. The association between Doppler indices and STV values with adverse perinatal outcome was analyzed using univariate regression analysis.ResultsNo significant association between Doppler parameters and the need for secondary cesarean delivery (CD) or operative vaginal delivery (OVD) was shown. Regarding fetuses delivered by CD due to fetal distress, regression analyzes revealed significantly higher UA PI MoM. However, the differences in MCA PI MoM and CPR MoM were not statistically significant. Fetuses with the need for emergency CD showed significantly higher UA PI MoM, lower MCA PI MoM and lower CPR MoM. Neonates with a 5-min Apgar score <7 had significantly lower MCA PI MoM and neonatal acidosis (UA pH 7.10) showed a significant association with UA PI MoM. None of the assessed outcome parameters were significantly associated to STV.ConclusionDoppler indices assessed close to delivery in low-risk fetuses at term show a moderate association with adverse outcome parameters,whereas STV does not appear to predict poor perinatal outcome in this group of fetuses.
CRIS-Team WoS Importer:2019-03-08

Correlation of short-term variation and Doppler parameters with adverse perinatal outcome in small-for-gestational age fetuses at term - Stumpfe, Florian M.; Faschingbauer, Florian; Kehl, Sven; Pretscher, Jutta; Stelzl, Patrick; Mayr, Andreas; Schild, Ralf L.; Schmid, Matthias; Beckmann, Matthias; Schneider, Michael (Archives of Gynecology and Obstetrics, 2019)
Objective: To evaluate the association of short-term variation (STV) and Doppler parameters with adverse perinatal outcome in small-for-gestational-age (SGA) fetuses at term. Methods: In this retrospective single-center study 97 patients with singleton SGA fetuses at term (≥ 37 + 0 weeks’ gestation) were examined. Inclusion criteria were a birth weight < 10th centile, cephalic presentation and planned vaginal birth. Only cases with available Doppler measurements of umbilical artery (UA) and middle cerebral artery (MCA) with calculated cerebroplacental ratio (CPR) in combination with a computerized CTG (cCTG) and STV 72 h prior to delivery were eligible for analysis. Pulsatility indices (PI) were converted into multiples of median (MoM), adjusted for gestational age. The association between Doppler indices and STV values with mode of delivery [secondary cesarean delivery (CD), operative vaginal delivery (OVD), as well as secondary CD and OVD due to fetal distress] and neonatal outcome [UA blood pH ≤ 7.15 and the need of admission to the neonatal intensive care unit (NICU)] was analyzed using logistic regression analysis. Results: There was a significant association between UA PI MoM and the rate of CD. CD due to fetal distress, OVD and OVD due to fetal distress did not show a correlation with the evaluated Doppler parameters. Furthermore, we did not find an association between low UA birth pH and Doppler parameters while neonates with the need of admission to NICU had significant higher UA PI MoM and significant lower MCA PI MoM and CPR MoM. Regarding STV, a significant effect of low STV on NICU admission was found while none of the other assessed outcome parameters were significantly associated with STV. Conclusion: STV and Doppler parameters in SGA fetuses at term are significantly associated to the rate of NICU admission.
CRIS-Team Scopus Importer:2019-07-09
Keywords: Cardiotocography; Cerebroplacental ratio; Computerized CTG; Doppler; Fetal distress; SGA; Short-term variation; small-for-gestational age

Corrigendum to “A randomised phase II study investigating durvalumab in addition to an anthracycline taxane-based neoadjuvant therapy in early triple-negative breast cancer: clinical results and biomarker analysis of GeparNuevo study”: [Annals of Oncology (2019), volume 30:1279-1288, (Annals of Oncology (2019) 30(1279-1288) (S0923753419312785)) - Loibl, S.; Untch, M.; Burchardi, N.; Huober, J.; Sinn, B. V.; Blohmer, J. U.; Grischke, E. M.; Furlanetto, J.; Tesch, H.; Hanusch, C.; Engels, K.; Rezai, M.; et al. (Annals of Oncology, 2022)
The authors regret that in the original publication Fig. 3 was incorrectly presented. The correct figure is as below. The following corrections were made: - In figure 3A, part “additional TIL parameters”, box “iTILs postTx”: The number of patients was N=82 (not N=84 as published).- In figure 3B, row “Durvalumab-arm, sTILs preTx”, column “OR”: The estimated odds ratio was 1.29 (not 1.23 as published). This correction also affects the graphical representation left to column “OR”: The diamond marker must be in the center of the line.The authors would like to apologize for any inconvenience caused.[Formula presented]
CRIS-Team Scopus Importer:2022-11-11

Corrigendum to “Initial experience with CDK4/6 inhibitor-based therapies compared to antihormone monotherapies in routine clinical use in patients with hormone receptor positive, HER2 negative breast cancer — Data from the PRAEGNANT research network for the first 2 years of drug availability in Germany” (The Breast (2020) 54 (88–95), (S0960977620301648), (10.1016/j.breast.2020.08.011)) - Schneeweiss, Andreas; Ettl, Johannes; Lüftner, Diana; Beckmann, Matthias; Belleville, Erik; Fasching, Peter; Fehm, Tanja N.; Geberth, Matthias; Häberle, Lothar; Hadji, Peyman; Hartkopf, Andreas D.; Hielscher, Carsten; et al. (BREAST, 2021)
In Fig. 2c and f of our publication Schneeweiss et al. [1] we mistakenly placed wrong Kaplan Meier Plots. In the attached figure this was corrected. All other estimates concerning the survival including the regression models are correct. We apologize for the mistake. 1. Schneeweiss A, Ettl J, Luftner D et al. Initial experience with CDK4/6 inhibitor-based therapies compared to antihormone monotherapies in routine clinical use in patients with hormone receptor positive, HER2 negative breast cancer - Data from the PRAEGNANT research network for the first 2 years of drug availability in Germany. Breast 2020; 54: 88–95.Fig. 2. Progression-free survival (PFS) and overall survival (OS) for the total group analyzed. CDK4/6i, CDK4/6 inhibitors; ET, endocrine therapy; OS, overall survival; PFS, progression-free survival. [Table presented]
CRIS-Team Scopus Importer:2021-01-15

Corrigendum to Rationale and trial design of NATALEE: a Phase III trial of adjuvant ribociclib + endocrine therapy versus endocrine therapy alone in patients with HR+/HER2- early breast cancer. - Slamon, Dennis J.; Fasching, Peter; Hurvitz, Sara (Therapeutic Advances in Medical Oncology, 2023)
[This corrects the article DOI: 10.1177/17588359231178125.].
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Corrigendum to ‘Ribociclib plus fulvestrant for postmenopausal women with hormone receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer in the phase III randomized MONALEESA-3 trial: updated overall survival’: [Annals of Oncology Volume 32, Issue 8, August 2021, Pages 1015-1024] (Annals of Oncology (2021) 32(8) (1015–1024), (S0923753421015532), (10.1016/j.annonc.2021.05.353)) - Slamon, D. J.; Neven, P.; Chia, S.; Jerusalem, G.; De Laurentiis, M.; Im, S.; Petrakova, K.; Valeria Bianchi, G.; Martín, M.; Nusch, A.; Sonke, G. S.; De la Cruz-Merino, L.; et al. (Annals of Oncology, 2021)
The authors regret that at the time the article was published, Supplementary Table S2 contained errors. This has now been corrected. The authors would like to apologise for any inconvenience caused.
CRIS-Team Scopus Importer:2021-08-27

Cost effectiveness of bilateral risk-reducing mastectomy and salpingo-oophorectomy - Schrauder, Michael G.; Brunel-Geuder, Lisa; Häberle, Lothar; Wunderle, Marius; Hoyer, Juliane; Csorba, Roland; Reis, André; Schulz-Wendtland, Rüdiger; Beckmann, Matthias; Lux, Michael P. (European Journal of Medical Research, 2019)
BACKGROUND: Growing demand for risk-reducing surgery in individuals with inherited susceptibility to cancer leads to the question whether these procedures are cost effective for the executing hospitals. This study compared the clinical costs for bilateral risk-reducing mastectomy (BRRM) with and without different types of reconstruction, risk-reducing salpingo-oophorectomy (RRSO), and their combinations with corresponding reimbursements in the statutory health-care system in Germany. PATIENTS AND METHODS: Real total costs of care for BRRM with and without reconstruction, RRSO, and their combinations were calculated as the sum of all personnel and technical costs. These costs calculated in a German University hospital were compared with the sum of all reimbursements in the German DRG-based health-care system. RESULTS: While sole RRSO, BRRM without reconstruction, and BRRM with secondary DIEP (deep inferior epigastric perforator)-reconstruction still result in a small benefit, we even found shortfalls for the hospital with all other prophylactic operations under consideration. The calculated deficits were especially high for BRRM with implant-based breast reconstruction and for combined operations when the risk reduction is achieved with a minimum of separate operations. CONCLUSIONS: Risk-reducing surgery in BRCA-mutation carriers is frequently not cost-covering for the executing hospitals in the German health-care system. Thus, appropriate concepts are required to ensure a nationwide care.
CRIS-Team Scopus Importer:2019-09-24
Keywords: BRCA; Breast cancer; Cost effectiveness; Genetic counseling; Ovarian cancer

Cost-Effectiveness of Neoadjuvant Pembrolizumab Plus Chemotherapy Followed by Adjuvant Single-Agent Pembrolizumab for High-Risk Early-Stage Triple-Negative Breast Cancer in the United States - Huang, Min; Fasching, Peter; Haiderali, Amin; Xue, Weiguang; Yang, Chelsey; Pan, Wilbur; Zhou, Zheng Yi; Hu, Peter; Chaudhuri, Mitashri; Le Bailly De Tilleghem, Celine; Cappoen, Nicolas; O’Shaughnessy, Joyce (Advances in Therapy, 2023)
Introduction: The randomized phase III KEYNOTE-522 trial demonstrated that addition of pembrolizumab to neoadjuvant chemotherapy provided a significant improvement in event-free survival and a favorable trend in overall survival for high-risk early-stage triple-negative breast cancer (eTNBC). This analysis evaluated the cost-effectiveness of pembrolizumab in combination with chemotherapy as neoadjuvant treatment and continued as a single-agent adjuvant treatment after surgery vs. neoadjuvant chemotherapy for patients with high-risk eTNBC in the USA. Methods: The analysis was conducted from a US third-party public healthcare payer perspective. A multistate transition model was developed using efficacy and safety data from the KEYNOTE-522 trial. The model included four mutually exclusive health states: event-free, locoregional recurrence, distant metastasis, and death to simulate patients’ lifetime disease course. Quality-adjusted life years (QALYs) were calculated on the basis of EuroQoL-5 Dimensions utility data collected in KEYNOTE-522. Costs for drug acquisition/administration, adverse events, disease management, and subsequent therapies were reported (2021 US dollars). Costs and outcomes were discounted at 3% annually. A series of sensitivity analyses were performed to test the robustness of the main results. Results: In the base case scenario, pembrolizumab plus chemotherapy followed by pembrolizumab resulted in expected gains of 3.37 life years (LYs) and 2.90 QALYs, and an incremental cost of 79,046 versus chemotherapy. The incremental cost per QALY gained was 27,285, which is lower than all commonly cited US willingness-to-pay thresholds. Sensitivity analyses showed the results were robust over plausible values of key model inputs and assumptions. Conclusions: Compared with neoadjuvant chemotherapy, pembrolizumab in combination with chemotherapy as neoadjuvant treatment and continued as a single-agent adjuvant treatment after surgery is considered a cost-effective option for high-risk eTNBC in the USA.
CRIS-Team Scopus Importer:2023-01-27
Keywords: Adjuvant therapy; Cost-effectiveness analysis; Early-stage triple-negative breast cancer; Neoadjuvant therapy; Pembrolizumab

COST EFFECTIVENESS OF PEMBROLIZUMAB COMBINED WITH CHEMOTHERAPY VS. CHEMOTHERAPY AS FIRST-LINE TREATMENT FOR METASTATIC TNBC THAT EXPRESSES PD-L1 IN THE UNITED STATES - Huang, M.; Fasching, Peter; Haiderali, A.; Pan, W.; Gray, E.; Zhou, J.; Hu, P. H.; De Tilleghem, Le Bailly C.; Cappoen, N.; Chaudhuri, M.; O'Shaughnessy, J. (VALUE IN HEALTH, 2022)
CRIS-Team WoS Importer:2022-08-26

Cost effectiveness of pembrolizumab in combination with chemotherapy as neoadjuvant therapy and continued as a single agent as adjuvant therapy for high-risk early-stage TNBC in the United States - Fasching, Peter; Huang, M.; Haiderali, A.; Xue, W.; Pan, W.; Zhou, Z-Y.; Hu, P.; Chaudhuri, M.; De Tilleghem, C. Le Bailly; Cappoen, N.; O'Shaughnessy, J. (ANNALS OF ONCOLOGY, 2022)
CRIS-Team WoS Importer:2022-06-03

Cost-effectiveness of pembrolizumab plus chemotherapy as first-line treatment in PD-L1-positive metastatic triple-negative breast cancer - Huang, Min; Fasching, Peter; Haiderali, Amin; Pan, Wilbur; Gray, Emma; Zhou, Zheng-Yi; Hu, Peter; Chaudhuri, Mitashri; De Tilleghem, Celine Le Bailly; Cappoen, Nicolas; O'Shaughnessy, Joyce (Immunotherapy, 2022)
Objective: This study evaluated the cost-effectiveness of pembrolizumab/chemotherapy combinations for previously untreated metastatic triple-negative breast cancer patients in the USA with PD-L1 combined positive score >= 10. Methods: A partitioned-survival model was developed to project health outcomes and direct medical costs over a 20-year time horizon. Efficacy and safety data were from randomized clinical trials. Comparative effectiveness of indirect comparators was assessed using network meta-analyses. A series of sensitivity analyses were performed to test the robustness of the results. Results: Pembrolizumab/chemotherapy resulted in total quality-adjusted life-year (QALY) gains of 0.70 years and incremental cost-effectiveness ratio of US182,732/QALY compared with chemotherapy alone. The incremental cost-effectiveness ratio for pembrolizumab/nab-paclitaxel versus atezolizumab/nab-paclitaxel was US44,157/QALY. Sensitivity analyses showed the results were robust over plausible values of model inputs. Conclusion: Pembrolizumab/chemotherapy is cost effective compared with chemotherapy as well as atezolizumab/nab-paclitaxel as first-line treatment for PD-L1-positive metastatic triple-negative breast cancer from a US payer perspective.
CRIS-Team WoS Importer:2022-07-15

Cost-effectiveness of risk-reducing surgeries in preventing hereditary breast and ovarian cancer - Schrauder, Michael G.; Brunel-Geuder, Lisa; Häberle, Lothar; Wunderle, Marius; Hoyer, Juliane; Wiesmann da Silva Reis, André; Schulz-Wendtland, Rüdiger; Beckmann, Matthias; Lux, Michael P. (BREAST, 2017)
Risk-reducing surgeries are a feasible option for mitigating the risk in individuals with inherited susceptibility to cancer, but are the procedures cost-effective in the current health-care system in Germany? This study compared the health-care costs for bilateral risk-reducing mastectomy (BRRM) and risk-reducing (bilateral) salpingo-oophorectomy (RRSO) with cancer treatment costs that could potentially be prevented.The analysis is based on interdisciplinary consultations with individuals with a high familial risk for breast and ovarian cancer at the University Breast Center for Franconia (Germany) between 2009 and 2013 (370 consultations; 44 patients with BRCA1 mutations and 26 with BRCA2 mutations). Health-care costs for risk-reducing surgeries in BRCA mutation carriers were calculated as reimbursements in the German diagnosis-related groups (DRG) hospital pricing system. These costs for the health-care system were compared with the potential cancer treatment costs that could possibly be prevented by risk-reducing surgeries.Long-term health-care costs can be reduced by risk-reducing surgeries after genetic testing in BRCA mutation carriers. The health-care system in Germany would have saved EUR 136,295 if BRRM had been performed and EUR 791,653 if RRSO had been performed before the development of cancer in only 50% of the 70 mutation carriers seen in our center. Moreover, in patients with combined RRSO and BRRM (without breast reconstruction), one further life-year for a 40-year-old BRCA mutation carrier would cost EUR 2,183.Intensive care, including risk-reducing surgeries in BRCA mutation carriers, is cost-effective from the point of view of the health-care system in Germany.
EVALuna2:9369

Cranial and cerebral signs in the diagnosis of spina bifida between 18 and 22 weeks of gestation: a German multicentre study - Bahlmann, F.; Reinhard, I.; Schramm, T.; Geipel, A.; Gembruch, U.; Von Kaisenberg, C. S.; Schmitz, R.; Stupin, J.; Chaoui, R.; Karl, K.; Kalache, K.; Faschingbauer, Florian; et al. (Prenatal Diagnosis, 2015)
The aim of this article is to study secondary cranial signs in fetuses with spina bifida in a precisely defined screening period between 18 + 0 and 22 + 0 weeks of gestation.On the basis of retrospective analysis of 627 fetuses with spina bifida, the value of indirect cranial and cerebral markers was assessed by well-trained ultrasonographers in 13 different prenatal centres in accordance with the ISUOG (International Society of Ultrasound in Obstetrics and Gynecology) guidelines on fetal neurosonography.Open spina bifida was diagnosed in 98.9% of cases whereas 1.1% was closed spina bifida. Associated chromosomal abnormalities were found in 6.2%. The banana and lemon signs were evident in 97.1% and 88.6% of cases. Obliteration of the cisterna magna was seen in 96.7%. Cerebellar diameter, head circumference and biparietal diameter were below the 5th percentile in chromosomally normal fetuses in 72.5%, 69.7% and 52%, respectively. The width of the posterior horn of the lateral ventricle was above the 95th percentile in 57.7%. The secondary cranial and cerebral signs were dependent on fetal chromosome status and width of the posterior horn. Biparietal diameter was also dependent on the chromosome status with statistical significance p = 0.0068. Pregnancy was terminated in 89.6% of cases.In standard measuring planes, lemon sign, banana sign and an inability to image the cistern magna are very reliable indirect ultrasound markers of spina bifida. © 2014 John Wiley & Sons, Ltd.
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Cross-Cancer Genome-Wide Association Study of Endometrial Cancer and Epithelial Ovarian Cancer Identifies Genetic Risk Regions Associated with Risk of Both Cancers - Glubb, Dylan M.; Thompson, Deborah J.; Aben, Katja K. H.; Alsulimani, Ahmad; Amant, Frederic; Annibali, Daniela; Attia, John; Barricarte, Aurelio; Beckmann, Matthias; Berchuck, Andrew; Bermisheva, Marina; Bernardini, Marcus Q.; et al. (Cancer Epidemiology Biomarkers & Prevention, 2021)
Background: Accumulating evidence suggests a relationship between endometrial cancer and ovarian cancer. Independent genome-wide association studies (GWAS) for endometrial cancer and ovarian cancer have identified 16 and 27 risk regions, respectively, four of which overlap between the two cancers. We aimed to identify joint endometrial and ovarian cancer risk loci by performing a meta-analysis of GWAS summary statistics from these two cancers.
CRIS-Team WoS Importer:2021-03-12

Cullin 7 and Fbxw 8 expression in trophoblastic cells is regulated via oxygen tension: Implications for intrauterine growth restriction - Fahlbusch, Fabian; Dawood, Yousif Louay; Hartner, Andrea; Menendez-Castro, Carlos; Nögel, Stephanie; Tzschoppe, Anja; Schneider, Holm; Strissel, Pamela; Beckmann, Matthias; Schleussner, Ekkehard; Rübner, Matthias; Dörr, Helmuth-Günther; et al. (Journal of Maternal-Fetal & Neonatal Medicine, 2012)
Objective: The F-box protein Fbxw8 is a cofactor of Cullin 7 (Cul7), which regulates protein transfer to the proteasome and cell growth. Cul7 or Fbxw8 deficiency is associated with intrauterine growth restriction (IUGR) due to abnormal placental development leading to poor oxygen supply to the fetus. We studied the role of hypoxia for Fbxw8 and Cul7 expression in trophoblastic cells. Methods: Immunomagnetic bead-separated extravillous trophoblast (EVT) and villous trophoblast (VT) and trophoblast cell lines were incubated with 1 or 8% O2. Fbxw8 and Cul7 expression was determined in IUGR versus matched control placentas. Results: Fbxw8 was expressed uniformly in trophoblasts, whereas Cul7 expression was most prominent in trophoblast cell lines. Hypoxia reduced expression of Cul7 and Fbxw8 in all trophoblastic cells, except for villous trophoblasts. In vivo, Cul7 and Fbxw8 were detected in syncytiotrophoblast cells, VT, and EVT cells. Although no significant changes in expression levels of Fbxw8 or Cul7 were noted in IUGR compared with control placentas, Fbxw8 expression correlated negatively with gestational age in the control, but not in the IUGR group. Conclusion: Fbxw8 and Cul7 expression reveals a complex regulation in trophoblastic cells. Our findings suggest that dysregulation of Cul7 and Fbxw8 expression might affect trophoblast turnover in IUGR. © 2012 Informa UK, Ltd.
CRIS-Team Scopus Importer:2020-07-01
Keywords: Cul7; Fbxw8; IUGR; Oxygen; Placenta; Trophoblast

Culture of Individually Required Number of 2-Pronuclei-Stage Oocytes - Patient Participation in Decision-Making is in Accordance with the Aim of Avoiding Surplus Embryo Freezing - Cupisti, Susanne; Mueller, A.; Hildebrandt, T.; Hackl, J.; Beckmann, Matthias; Dittrich, Ralf (Geburtshilfe und Frauenheilkunde, 2014)
Background: The aim of this study was to evaluate how many embryos will develop if more than 3 2-pronuclei-stage oocytes (2-PNOs) are cultured at the patient's request and in accordance with the Germany Embryo Protection Law. Methods: A total of 106 cycles of patients undergoing their 1st, 2nd or 3rd cycle of IVF or ICSI treatment in 2010 were prospectively included in the study. In each individual case, a decision was taken prior to treatment about the number of 2-PNOs to be cultured after each cycle. Results: Ninety female patients were treated for a total of 106 cycles. A mean of two to six 2-PNOs were cultivated for a period of between 3 and 6 days for each patient. After culture, no viable embryo was identified for 5 patients (4.7 %), a single viable embryo was identified for 37 cycles (34.7 %), and 2 viable embryos were identified for 52 cycles (48.8 %). Eleven patients (10.3 %) had 3 viable embryos after a further 11 cycles and 1 patient had 4 viable embryos in a single cycle. Ten of the patients with 3 embryos each opted to have all 3 embryos transferred in the same cycle. This meant that a single embryo from one patient with 3 viable embryos and a single embryo of the patient with 4 viable embryos were cryopreserved after culture. The pregnancy rate was 19 % per embryo transfer and 25 % per blastocyst transfer (20 pregnancies in total). All cryopreserved embryos were transferred in a subsequent cycle. Discussion: Based on this study it is possible to make a statement about the number of viable embryos which should be cultivated to obtain, at best, two embryos for transfer without running an unacceptably high risk of producing too many embryos which would then need to be cryopreserved. Only 12 patients (13.3 %) had more than 2 viable embryos. The number of supernumerary pre-implantation-stage embryos was acceptably low (only 2 patients had additional viable embryos, 2.2 %). This means that it is possible to fulfil the wishes of individual patients while complying with the German Embryo Protection Law.
EVALuna2:17451

Current landscape of hospital information systems in gynecology and obstetrics in Germany: a survey of the commission Digital Medicine of the German Society for Gynecology and Obstetrics - Pfob, André; Griewing, Sebastian; Seitz, Katharina; Hillen, Christoph; Becker, Sven; Bayer, Christian; Wagner, Uwe; Fasching, Peter; Wallwiener, Markus; Abele, Harald; Alexa, Matthias; Cieslik, Jan Philipp; et al. (Archives of Gynecology and Obstetrics, 2023)
Purpose: Hospital information systems (HIS) play a critical role in modern healthcare by facilitating the management and delivery of patient care services. We aimed to evaluate the current landscape of HIS in the specialty of gynecology and obstetrics in Germany. Methods: An anonymous questionnaire was distributed via the German Society of Gynecology and Obstetrics newsletter in December 2022. The questionnaire covered the domains baseline demographic information, satisfaction with daily use, satisfaction with implementation, and degree of digitization. Results: Ninety-one participants completed the survey. Median age was 34 years; 67.4% (60 of 89) were female, and 32.6% (29 of 89) were male. Of the survey participants, 47.7% (42 of 88) were residents, 26.1% (23 of 91) senior physicians, and 9.1% (8 of 88) medical directors. The degree of digitization of clinical documentation is mainly mixed digital and paper-based (64.0%, 57 of 89) while 16.9% (15 of 89) operate mainly paper-based. The current HIS has been in use on average for 9 years. The median number of different software systems used in daily routine is 4. About 33.7% (30 of 89) would likely or very likely recommend their current HIS to a colleague. Conclusions: The current landscape of HIS in gynecology and obstetrics in Germany is characterized by a high heterogeneity of systems with low interoperability and long service life; thus, many healthcare professionals are not satisfied. There is both a need to enhance and an interest in modernizing the technological infrastructure to meet today’s requirements for patient care.
CRIS-Team Scopus Importer:2023-11-03
Keywords: Artificial intelligence; Digital health; eHealth; Gynecology and obstetrics; Implementation

CYP19A1 fine-mapping and Mendelian randomization: estradiol is causal for endometrial cancer - Thompson, Deborah J.; O'Mara, Tracy A.; Glubb, Dylan M.; Painter, Jodie N.; Cheng, Timothy; Folkerd, Elizabeth; Doody, Deborah; Dennis, Joe; Webb, Penelope M.; Gorman, Maggie; Martin, Lynn; Hodgson, Shirley; et al. (Endocrine-Related Cancer, 2016)
Candidate gene studies have reported CYP19A1 variants to be associated with endometrial cancer and with estradiol (E2) concentrations. We analyzed 2937 single nucleotide polymorphisms (SNPs) in 6608 endometrial cancer cases and 37 925 controls and report the first genome wide-significant association between endometrial cancer and a CYP19A1 SNP (rs727479 in intron 2, P=4.8×10(-11)). SNP rs727479 was also among those most strongly associated with circulating E2 concentrations in 2767 post-menopausal controls (P=7.4×10(-8)). The observed endometrial cancer odds ratio per rs727479 A-allele (1.15, CI=1.11-1.21) is compatible with that predicted by the observed effect on E2 concentrations (1.09, CI=1.03-1.21), consistent with the hypothesis that endometrial cancer risk is driven by E2. From 28 candidate-causal SNPs, 12 co-located with three putative gene-regulatory elements and their risk alleles associated with higher CYP19A1 expression in bioinformatical analyses. For both phenotypes, the associations with rs727479 were stronger among women with a higher BMI (Pinteraction=0.034 and 0.066 respectively), suggesting a biologically plausible gene-environment interaction.
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CYP2B6*6 is associated with increased breast cancer risk - Justenhoven, Christina; Pentimalli, Daniela; Rabstein, Sylvia; Harth, Volker; Lotz, Anne; Pesch, Beate; Bruening, Thomas; Doerk, Thilo; Schuermann, Peter; Bogdanova, Natalia; Park-Simon, Tjoung-Won; Couch, Fergus J.; et al. (International Journal of Cancer, 2014)
The cytochrome P450 2B6 (CYP2B6) is involved in the metabolism of testosterone. Functional changes in this enzyme may influence endogenous hormone exposure, which has been associated with risk of breast cancer. To assess potential associations between two functional polymorphisms CYP2B6_516_G>T (rs3745274) and CYP2B6_785_A>G (rs2279343) and breast cancer risk, we established a specific matrix-assisted laser desorption/ionization time-of-flight mass spectrometry assay. The GENICA breast cancer case-control study showed associations between the variant genotypes CYP2B6_516_TT and CYP2B6_785_GG and breast cancer risk with odds ratios (ORs) of 1.34 (p = 0.001) and 1.31 (p = 0.002), respectively. A similar effect was observed for carriers of the CYP2B6_516_T allele in a validation study including four independent studies from Germany, Sweden and USA. In a pooled analysis of all five studies involving 4,638 breast cancer cases and 3,594 controls of European ancestry, carriers of the CYP2B6_516_G and the CYP2B6_785_G variant had an increased breast cancer risk with ORs of 1.10 (p = 0.027) and 1.10 (p = 0.031), respectively. We conclude that the genetic variants CYP2B6_516_G and CYP2B6_785_G (designated CYP2B6*6), which are known to decrease activity of the CYP2B6 enzyme, contribute to an increased breast cancer risk.
EVALuna2:9206

CYP2D6 genotype and adjuvant tamoxifen: meta-analysis of heterogeneous study populations - Province, M. A.; Goetz, M. P.; Brauch, H.; Flockhare, D. A.; Hebert, J. M.; Whaley, R.; Suman, V. J.; Schroth, W.; Winter, S.; Zembutsu, H.; Mushiroda, Taisei; Newman, W. G.; et al. (Clinical Pharmacology & Therapeutics, 2014)
The International Tamoxifen Pharmacogenomics Consortium was established to address the controversy regarding cytochrome P450 2D6 (CYP2D6) status and clinical outcomes in tamoxifen therapy. We performed a meta-analysis on data from 4,973 tamoxifen-treated patients (12 globally distributed sites). Using strict eligibility requirements (postmenopausal women with estrogen receptor-positive breast cancer, receiving 20 mg/day tamoxifen for 5 years, criterion 1); CYP2D6 poor metabolizer status was associated with poorer invasive disease-free survival (IDFS: hazard ratio = 1.25; 95% confidence interval = 1.06, 1.47; P = 0.009). However, CYP2D6 status was not statistically significant when tamoxifen duration, menopausal status, and annual follow-up were not specified (criterion 2, n = 2,443; P = 0.25) or when no exclusions were applied (criterion 3, n = 4,935; P = 0.38). Although CYP2D6 is a strong predictor of IDFS using strict inclusion criteria, because the results are not robust to inclusion criteria (these were not defined a priori), prospective studies are necessary to fully establish the value of CYP2D6 genotyping in tamoxifen therapy.
EVALuna2:17447

Cytology and High-Risk Human Papillomavirus Test for Cervical Cancer Screening Assessment - Stübs, Frederik; Koch, Martin C.; Dietl, Anna; Adler, Werner; Geppert, Carol-Immanuel; Hartmann, Arndt; Knöll, Antje; Beckmann, Matthias; Mehlhorn, Grit; Schulmeyer, Carla; Gaß, Paul (Diagnostics, 2022)
Background: A new nationwide screening strategy was implemented in Germany in January 2020. No data are available for women referred to certified dysplasia units for secondary clarification after primary diagnosis by a local physician. We therefore investigated combined testing with Papanicolaou smears and high-risk human papillomavirus (hrHPV) and compared the data with the final histological findings. Methods: Between January 2015 and October 2020, all referred women who underwent colposcopy of the uterine cervix in our certified dysplasia unit were included. Cytology findings were classified using the Munich III nomenclature. Results: A total of 3588 colposcopies were performed in 3118 women, along with Pap smear and hrHPV co-testing, followed by histology. Women with Pap II-p (ASC-US) and a positive hrHPV co-test had a 22.4% risk for cervical intraepithelial neoplasia (CIN) 3/high-grade squamous intraepithelial lesion (HSIL). The risk of CIN 3/HSIL was 83.8% in women with Pap IVa-p (HSIL) and a positive hrHPV co-test. A positive hrHPV co-test increased the risk for HSIL+ (OR 5.942; 95% CI, 4.617 to 7.649; p < 0.001) as compared to a negative hrHPV co-test. Conclusions: The accuracy of Pap smears is comparable with the screening results. A positive hrHPV test increases the risk for HSIL+ fivefold. Colposcopy is necessary to diagnose HSIL+ correctly.
CRIS-Team WoS Importer:2022-08-12

Cytology and HPV Co-Testing for Detection of Vaginal Intraepithelial Neoplasia: A Retrospective Study. - Stübs, Frederik; Dietl, Anna; Koch, Martin C.; Adler, Werner; Geppert, Carol-Immanuel; Hartmann, Arndt; Knöll, Antje; Mehlhorn, Grit; Beckmann, Matthias; Schulmeyer, Carla; Heindl, Felix; Emons, Julius; et al. (Cancers, 2023)
(1) Background: Vaginal intraepithelial neoplasia (VaIN) is a rare premalignant disease caused by persistent human papillomavirus (HPV) infection. Diagnosing VaIN is challenging; abnormal cytology and positive HPV tests are usually the first signs, but published data on their accuracy for detecting it are rare and contradictory. The aim of this study is to compare the results of hrHPV and cytology co-testing with the histological findings of the vagina. (2) Methods: In the certified Dysplasia Unit at Erlangen University Hospital, cytology and HPV samples from the uterine cervix or vaginal wall after hysterectomy were obtained between 2015 and 2023 and correlated with histological findings in biopsies from the vaginal wall. Women without vaginal biopsy findings or concomitant cervical disease were excluded. (3) Results: In all, 279 colposcopies in 209 women were included. The histological results were: benign (n = 86), VaIN I/vLSIL (n = 116), VaIN II/vHSIL (n = 41), VaIN III/vHSIL (n = 33), and carcinoma (n = 3). Accuracy for detecting VaIN was higher in women with previous hysterectomies. Positive HPV testing during colposcopy increased the likelihood for VaIN II/III/vHSIL threefold. The detection rate for VaIN III/vHSIL was 50% after hysterectomy and 36.4% without hysterectomy. (4) Conclusions: Women with risk factors for VaIN, including HPV-16 infection or prior HPV-related disease, need careful work-up of the entire vaginal wall. Hysterectomy for HPV-related disease and a history of cervical intraepithelial neoplasia (CIN) also increased the risk for VaIN II/III/vHSIL.
EVALuna2:540622

Cytology and hrHPV for cervical cancer screening assessment - Stübs, Frederik; Koch, M. C.; Dietl, Anna; Adler, Werner; Geppert, Carol-Immanuel; Hartmann, Arndt; Knöll, Antje; Beckmann, Matthias; Mehlhorn, G.; Gaß, Paul; Schulmeyer, Carla (GEBURTSHILFE UND FRAUENHEILKUNDE, 2022)
CRIS-Team WoS Importer:2022-11-04

DasPAQT: Treating patients with Chronic Myeloid Leukemia (CML) in Chronic Phase (CP) with Dasatinib: PCR-Monitoring, adherence, quality of life, therapy satisfaction (OMC 2014-I; BMS CA180-565) - an analysis of the first 150 patients - Tesch, H.; Pelz, H.; Janssen, J.; Hansen, R.; Fietz, T.; Anhuf, J.; Häberle, Lothar; Belleville, E.; Schardt, C.; Azeh,; Steinmetz, T. (2016)
EVALuna2:33454

DasPAQT: Treating Patients with Chronic Myeloid Leukemia (CML) in Chronic Phase (CP) with Dasatinib - PCR-Monitoring, Adherence, Quality of Life, Therapy Satisfaction (OMC 2014-I; BMS CA180-565) - Tesch, H.; Pelz, H.; Janssen, J.; Hansen, R.; Fietz, T.; Anhuf, J.; Häberle, Lothar; Belleville, E.; Steinmetz, T.; Azeh, I.; Schardt, C. (2016)
EVALuna2:33457

Deactivating attachment strategies associate with early processing of facial emotion and familiarity in middle childhood: an ERP study - Kungl, Melanie; Vrticka, Pascal; Heinisch, Christine; Beckmann, Matthias; Fasching, Peter; Ziegler, Clara; Spangler, Gottfried (Attachment and Human Development, 2022)
Neurophysiological evidence suggests associations between attachment and the neural processing of emotion expressions. This study asks whether this relationship is also evident in middle childhood, and how it is affected by facial familiarity. Attachment strategies (deactivation, hyperactivation) were assessed in 51 9- to 11-year olds using a story stem completion task. Event-related potentials (ERPs) were recorded during children's passive viewing of mother and stranger emotional faces (angry/happy). At the stage of facial information encoding (N250), attachment deactivation was associated with a pattern pointing to increased vigilance towards angry faces. Further, the attention-driven LPP was increased to happy mother faces as highly salient stimuli overall, but not in children scoring high on deactivation. These children did not discriminate between mothers' facial emotions and showed a general attentional withdrawal from facial stimuli. While our results on attachment deactivation support a two-stage processing model, no effect of hyperactivation was found.
CRIS-Team WoS Importer:2022-10-21

Design and Implementation of a Single Source Multipurpose Hospital-Wide Clinical Trial Registry - Sommer, Marcus; Kirchner, Melanie; Gulden, Christian; Egloffstein, Sainab; Lux, Michael P.; Beckmann, Matthias; Mackensen, Andreas; Prokosch, Hans-Ulrich (ICT FOR HEALTH SCIENCE RESEARCH, 2019)
CRIS-Team WoS Importer:2021-10-18

Design and Implementation of a Single Source Multipurpose Hospital-Wide Clinical Trial Registry - Sommer, Marcus; Kirchner, Melanie; Gulden, Christian; Egloffstein, Sainab; Lux, Michael P.; Beckmann, Matthias; Mackensen, Andreas; Prokosch, Hans-Ulrich (Studies in health technology and informatics, 2019)
IT-supported patient recruitment, serious adverse event reporting as well as making information about clinical trials accessible to the public on websites, are still major challenges in clinical trials. Too often the distribution of information about trials being performed within a hospital across numerous institutions and IT systems is a barrier to provide efficient IT support for such scenarios. Thus, the essential prerequisite to mastering those challenges is to achieve one single point of truth with adequate, complete, accurate and up-to-date information about all clinical trials running at a hospital. We describe the design and implementation of such a single source clinical trial registry serving multiple purposes at a university hospital.
CRIS-Team Scopus Importer:2019-05-02
Keywords: Clinical trials as topic; electronic health record; registries

Design and Implementation of a Single Source Multipurpose Hospital-Wide Clinical Trial Registry. - Sommer, Marcus; Kirchner, Melanie; Gulden, Christian; Egloffstein, Sainab; Lux, Michael P.; Beckmann, Matthias; Mackensen, Andreas; Prokosch, Hans-Ulrich (Studies in health technology and informatics, 2019)
IT-supported patient recruitment, serious adverse event reporting as well as making information about clinical trials accessible to the public on websites, are still major challenges in clinical trials. Too often the distribution of information about trials being performed within a hospital across numerous institutions and IT systems is a barrier to provide efficient IT support for such scenarios. Thus, the essential prerequisite to mastering those challenges is to achieve one single point of truth with adequate, complete, accurate and up-to-date information about all clinical trials running at a hospital. We describe the design and implementation of such a single source clinical trial registry serving multiple purposes at a university hospital.
EVALuna2:184246

Desire to Have Children Among Transgender People in Germany: A Cross-Sectional Multi-Center Study - Auer, Matthias K.; Fuss, Johannes; Nieder, Timo O.; Briken, Peer; Biedermann, Sarah; Stalla, Guenter K.; Beckmann, Matthias; Hildebrandt, Thomas (Journal of Sexual Medicine, 2018)
Many trans individuals undergo medical interventions that result in irreversible loss of fertility. Little is known about their desire to have children and attitudes toward fertility preservation options.To study how the desire for children and the use of fertility preservation options varies among trans women and trans men in different transitioning stages in Germany.In this cross-sectional multi-center study, N = 99 trans women and N = 90 trans men were included. Of these, 26 of each sex were just about to start medical treatment.Outcome parameter were the prevalence and determinants of a desire to have children in trans persons.Before treatment, a desire for children was significantly higher in trans men compared to trans women (P = .016). In contrast, in those who had already started treatment, a current desire to have children was equally present in about one fourth of participants of both genders while the interest in having children in the future was significantly higher in trans women (69.9%) than in trans men (46.9%; P = .034). Although 76.1% of trans women and 76.6% of trans men indicated that they had at least thought about preserving germ cells before starting medical transition, only 9.6% of trans women and 3.1% of trans men had put this idea into practice. Most trans men in both groups indicated that insemination of a female partner with sperm from an unrelated donor was a suitable option to fulfill their child wish, potentially explaining their low interest in preserving their own germ cells. Finally, a logistic regression analysis accounting for potential confounders revealed that overall trans women were more than twice as likely to have a current desire to have children (odds ratio 2.58), and this wish was on average 5.3% lower with each year of increasing age.A low level of fertility preservation among trans persons is contrasted by a high level of desire for children. This highlights the importance of counseling trans individuals regarding fertility preservation options.To our knowledge, this is the first study that addresses desire to have children in a clinical sample of trans women. It is also the first that investigates this issue among trans men who have not started medical treatment, and the first comparison of both genders. A limitation for the generalization of our results is the special legal context in Germany that forbids oocyte donation for reciprocal in vitro fertilization. Reproductive desire is high among trans individuals, but the use of reproductive options is surprisingly low. Auer MK, Fuss J, Nieder TO, et al. Desire to Have Children Among Transgender People in Germany: A Cross-Sectional Multi-Center Study. J Sex Med 2018;15:757-767.
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DETECT III und IV - Individualisierte CTC-basierte Therapie des HER2-negativen metastasierten Mammakarzinoms - Friedl, T. W. P.; Schneeweiss, A.; Mueller,; Riethdorf, S.; Pantel, K.; Taran, F-A; Polasik, A.; Tzschaschel, M.; Schochter, F.; De Gregorio, A.; Meier-Stiegen, F.; Fasching, Peter; et al. (GEBURTSHILFE UND FRAUENHEILKUNDE, 2020)
CRIS-Team WoS Importer:2020-07-31

Detection of circulating tumor cells using manually performed immunocytochemistry (MICC) does not correlate with outcome in patients with early breast cancer - Results of the German SUCCESS-A- trial - Jueckstock, Julia; Rack, Brigitte; Friedl, Thomas W. P.; Scholz, Christoph; Steidl, Julia; Trapp, Elisabeth; Tesch, Hans; Forstbauer, Helmut; Lorenz, Ralf; Rezai, Mahdi; Haeberle, Lothar; Alunni-Fabbroni, Marianna; et al. (BMC Cancer, 2016)
BACKGROUND: Recently, the prognostic significance of circulating tumor cells (CTCs) in primary breast cancer as assessed using the Food-and-Drug-Administration-approved CellSearch® system has been demonstrated. Here, we evaluated the prognostic relevance of CTCs, as determined using manually performed immunocytochemistry (MICC) in peripheral blood at primary diagnosis, in patients from the prospectively randomized multicenter SUCCESS-A trial (EudraCT2005000490-21). METHODS: We analyzed 23 ml of blood from 1221 patients with node-positive or high risk node-negative breast cancer before adjuvant taxane-based chemotherapy. Cells were separated using a density gradient followed by epithelial cell labeling with the anti-cytokeratin-antibody A45-B/B3, immunohistochemical staining with new fuchsin, and cytospin preparation. All cytospins were screened for CTCs, and the cutoff for positivity was at least one CTC. The prognostic value of CTCs with regard to disease-free survival (DFS), distant disease-free survival (DDFS), breast-cancer-specific survival (BCSS), and overall survival (OS) was assessed using both univariate analyses applying the Kaplan-Meier method and log-rank tests, and using multivariate Cox regressions adjusted for other predictive factors. RESULTS: In 20.6 % of all patients (n = 251) a median of 1 (range, 1-256) CTC was detected, while 79.4 % of the patients (n = 970) were negative for CTCs before adjuvant chemotherapy. A pT1 tumor was present in 40.0 % of patients, 4.8 % had G1 grading and 34.6 % were node-negative. There was no association between CTC positivity and tumor stage, nodal status, grading, histological type, hormone receptor status, Her2 status, menopausal status or treatment. Univariate survival analyses based on a median follow-up of 64 months revealed no significant differences between CTC-positive and CTC-negative patients with regard to DFS, DDFS, BCSS, or OS. This was confirmed by fully adjusted multivariate Cox regressions, showing that the presence of CTCs (yes/no) as assessed by MICC did not predict DFS, DDFS, BCSS or OS. CONCLUSIONS: We could not demonstrate prognostic relevance regarding CTCs that were quantified using the MICC method at the time of primary diagnosis in our cohort of early breast cancer patients. Further studies are necessary to evaluate if the presence of CTCs assessed using MICC has prognostic relevance, or can be used for risk stratification and treatment monitoring in adjuvant breast cancer. TRIAL REGISTRATION: The ClinicalTrial.gov registration ID of this prospectively randomized trial is NCT02181101 ; the (retrospective) registration date was June 2014 (study start date September 2005).
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Detection of ESR1 Mutations in Single Circulating Tumor Cells on Estrogen Deprivation Therapy but Not in Primary Tumors from Metastatic Luminal Breast Cancer Patients - Franken, André; Honisch, Ellen; Reinhardt, Florian; Meier-Stiegen, Franziska; Yang, Liwen; Jaschinski, Sandra; Esposito, Irene; Alberter, Barbara; Polzer, Bernhard; Hübner, Hanna; Fasching, Peter; Pancholi, Sunil; et al. (Journal of Molecular Diagnostics, 2020)
Mutations in the ligand-binding domain (LBD) of the ESR1 gene result in resistance to estrogen deprivation therapy (EDT) in breast cancer. Their detection might enable optimization of therapy strategies. However, the predictive utility of the primary tumor (PT) is limited, and obtaining serial biopsies of metastatic lesions is challenging. To underline their application as a liquid biopsy, single circulating tumor cells (CTCs) were analyzed with a next-generation sequencing approach for the ESR1 coding region. CTCs from 46 metastatic luminal breast cancer patients were enriched using CellSearch system and isolated by micromanipulation. Their genomic DNA was amplified and the ESR1 gene was sequenced. Furthermore, tissue samples from corresponding PTs and/or metastatic lesions were investigated. ESR1 mutations were detected in 12 patients—exclusively in patients treated with EDT (P = 0.048). In seven cases mutations were located in the hotspot regions in the LBD. Six novel mutations were identified. ESR1 mutations were absent in PT tissue samples and were detected only in metastases obtained after CTC characterization. Single-cell CTC analysis for ESR1 mutations could be of clinical value to identify patients who progress under EDT and therefore benefit from an early switch to an alternative endocrine therapy or other treatment regimens. Furthermore, our data indicate that mutations outside the LBD's hotspot regions might also contribute to resistance to EDT.
CRIS-Team Scopus Importer:2019-12-20

Detection of microcalcifications in spiral breast computed tomography with photon-counting detector is feasible: A specimen study - Wetzl, Matthias; Wenkel, Evelyn; Balbach, Eva; Dethlefsen, Ebba; Hartmann, Arndt; Emons, Julius; Kuhl, Christiane; Beckmann, Matthias; Uder, Michael; Ohlmeyer, Sabine (Diagnostics, 2021)
The primary objective of the study was to compare a spiral breast computed tomography system (SBCT) to digital breast tomosynthesis (DBT) for the detection of microcalcifications (MCs) in breast specimens. The secondary objective was to compare various reconstruction modes in SBCT. In total, 54 breast biopsy specimens were examined with mammography as a standard reference, with DBT, and with a dedicated SBCT containing a photon-counting detector. Three different reconstruction modes were applied for SBCT datasets (Recon1 = voxel size (0.15 mm)3, smooth kernel; Recon2 = voxel size (0.05 mm)3, smooth kernel; Recon3 = voxel size (0.05 mm)3, sharp kernel). Sensitivity and specificity of DBT and SBCT for the detection of suspicious MCs were analyzed, and the McNemar test was used for comparisons. Diagnostic confidence of the two readers (Likert Scale 1 = not confident; 5 = completely confident) was analyzed with ANOVA. Regarding detection of MCs, reader 1 had a higher sensitivity for DBT (94.3%) and Recon2 (94.9%) compared to Recon1 (88.5%; p < 0.05), while sensitivity for Recon3 was 92.4%. Respectively, reader 2 had a higher sensitivity for DBT (93.0%), Recon2 (92.4%), and Recon3 (93.0%) compared to Recon1 (86.0%; p < 0.05). Specificities ranged from 84.7–94.9% for both readers (p > 0.05). The diagnostic confidence of reader 1 was better with SBCT than with DBT (DBT 4.48 ± 0.88, Recon1 4.77 ± 0.66, Recon2 4.89 ± 0.44, and Recon3 4.75 ± 0.72; DBT vs. Recon1/2/3: p < 0.05), while reader 2 found no differences. Sensitivity and specificity for the detection of MCs in breast specimens is equal for DBT and SBCT when a small voxel size of (0.05 mm)3 is used with an equal or better diagnostic confidence for SBCT compared to DBT.
CRIS-Team Scopus Importer:2021-06-04
Keywords: Breast cancer; Microcalcifications; Reconstruction modes; Spiral breast CT

DETECT V/CHEVENDO - duale HER2-zielgerichteten Therapie mit Trastuzumab und Pertuzumab plus Ribociclib in Kombination mit Chemotherapie oder endokriner Therapie bei Patientinnen mit HER2-positivem und hormonrezeptor-positivem metastasierten Mammakarzinom - Friedl, T. W. P.; Polasik, A.; Tzschaschel, M.; Schochter, F.; De Gregorio, A.; Fasching, Peter; Taran, F-A; Schneeweiss, A.; Mueller,; Riethdorf, S.; Pantel, K.; Meier-Stiegen, F.; et al. (GEBURTSHILFE UND FRAUENHEILKUNDE, 2020)
CRIS-Team WoS Importer:2020-07-31

Determinants Affecting the Clinical Implementation of a Molecularly Informed Molecular Tumor Board Recommendation: Experience from a Tertiary Cancer Center. - Tögel, Lars; Schubart, Christoph; Lettmaier, Sebastian; Neufert, Clemens; Hoyer, Juliane; Wolff, Kerstin; Moskalev, Evgeny; Stöhr, Robert; Agaimy, Abbas; Wiesmann da Silva Reis, André; Wullich, Bernd; Mackensen, Andreas; et al. (Cancers, 2023)
Molecular Tumor Boards (MTBs) converge state-of-the-art next-generation sequencing (NGS) methods with the expertise of an interdisciplinary team consisting of clinicians, pathologists, human geneticists, and molecular biologists to provide molecularly informed guidance in clinical decision making to the treating physician. In the present study, we particularly focused on elucidating the factors impacting on the clinical translation of MTB recommendations, utilizing data generated from gene panel mediated comprehensive genomic profiling (CGP) of 554 patients at the MTB of the Comprehensive Cancer Center Erlangen, Germany, during the years 2016 to 2020. A subgroup analysis of cases with available follow-up data (n = 332) revealed 139 cases with a molecularly informed MTB recommendation, which was successfully implemented in the clinic in 44 (31.7%) of these cases. Here, the molecularly matched treatment was applied in 45.4% (n = 20/44) of cases for ≥6 months and in 25% (n = 11/44) of cases for 12 months or longer (median time to treatment failure, TTF: 5 months, min: 1 month, max: 38 months, ongoing at data cut-off). In general, recommendations were preferentially implemented in the clinic when of high (i.e., tier 1) clinical evidence level. In particular, this was the case for MTB recommendations suggesting the application of PARP, PIK3CA, and IDH1/2 inhibitors. The main reason for non-compliance to the MTB recommendation was either the application of non-matched treatment modalities (n = 30)/stable disease (n = 7), or deteriorating patient condition (n = 22)/death of patient (n = 9). In summary, this study provides an insight into the factors affecting the clinical implementation of molecularly informed MTB recommendations, and careful considerations of these factors may guide future processes of clinical decision making.
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Keywords: Molecular Tumor Board; clinical decision making; precision medicine; molecular pathology; real-world data; cancer care

Determinants of transplantation success with cryopreserved ovarian tissue: data from 196 women of the FertiPROTEKT network - Lotz, Laura; Bender-Liebenthron, J.; Dittrich, Ralf; Häberle, Lothar; Beckmann, Matthias; Germeyer, A.; Korell, M.; Saenger, N.; Kruessel, J. S.; Von Wolff, Michael (Human Reproduction, 2022)
STUDY QUESTION What are the pregnancy and live birth rates for ovarian tissue transplantation and which factors are associated with the success rate? SUMMARY ANSWER Pregnancy and live birth rates per transplanted woman are 32.7% and 26.5% and success rate is associated with female age and first versus repeated transplantation. WHAT IS KNOWN ALREADY Live birth rates after ovarian tissue transplantations have been reported to be between around 24% and 41% per patient. Success rates seem to be negatively associated with increasing female age at the time of tissue cryopreservation and with pelvic radiation. Success rates are apparently not reduced after overnight transportation of ovarian tissue before freezing. STUDY DESIGN, SIZE, DURATION Registry analysis of 244 transplantations in 196 women, performed by 26 FertiPROTEKT network centres from 2007 to 2019 with follow-up till December 2020. PARTICIPANTS/MATERIALS, SETTING, METHODS Orthotopic ovarian tissue transplantations were performed in 196 women, 191 with previous malignant and 5 with previous non-malignant diseases. Size of transplanting centres varied between 1 and 100 transplantations per centre (median: 2). Factors possibly associated with success rate such as female age, first and repeated transplantation, experience of the transplanting centre and overnight transportation of the ovarian tissue before freezing were analysed. MAIN RESULTS AND THE ROLE OF CHANCE Average age of all 196 transplanted women was 31.3 years (SD 5.2; range 17-44) at the time of cryopreservation of tissue and 35.9 years (SD 4.8; range 23-47) at the time of transplantation. Pregnancy rate was 30.6% (95% CI, 24.2-37.6%) per first transplantation and 32.7% (95% CI, 26.1-39.7%) per patient. Pregnancy rate was higher after first transplantation (30.6% (95% CI, 24.2-37.6%)) compared to second and subsequent transplantations (11.8% (95% CI, 3.3-27.5%)). Live birth rate per first transplantation was 25.0% (95% CI, 19.1-31.7%) and per patient 26.5% (95% CI, 20.5-33.3%). Success rate decreased with increasing age at the time of ovarian tissue freezing. Live birth rate was 28.2% (95% CI, 20.9-36.3%) in women <35 years and 16.7% (95% CI, 7.9-29.3%) in women >35 years. Pregnancy rates after first transplantation were higher in centres who had performed >= 10 transplantations (35.1%) compared to centres with <10 transplantation (25.4%) (P = 0.12). Corresponding live birth rates were 27.0% and 18.6%. Success rates were not different in women with and without overnight transportation of tissue before cryopreservation. LIMITATIONS, REASONS FOR CAUTION The data were drawn from a registry analysis. Data such as ovarian reserve and premature ovarian insufficiency were not available for all women. Data might be influenced by different follow-up policies of the centres. WIDER IMPLICATIONS OF THE FINDINGS The study reveals the high potential of ovarian tissue freezing and transplantation, but only if freezing is performed in younger women. The study suggests focus should be placed on the first and not on repeated transplantations. It also opens the discussion of whether transplantation should rather be performed by experienced centres. STUDY FUNDING/COMPETING INTEREST(S) No funding. No competing interests.
CRIS-Team WoS Importer:2022-11-04

Detyrosinated tubulin is decreased in fetal vessels of preeclampsia placentas - Huebner, H.; Knoerr, B.; Betzler, A.; Kehl, Sven; Baier, F.; Wachter, David Lukas; Strick, Reiner; Beckmann, Matthias; Fahlbusch, F. B.; Rübner, Matthias; Hartner, Andrea (Placenta, 2018)
INTRODUCTION: Preeclampsia is a hypertensive, gestational disease, which is still the leading cause of pregnancy related morbidity and mortality. The impairment of placental angiogenesis and vascularization is discussed to be of etiopathologic relevance. Deytrosination and tyrosination of α-tubulin is important for the stability and dynamics of microtubules. An increase of α-tubulin detyrosination leads to microtubule stabilization, which is an essential prerequisite for physiologic vascular tube morphogenesis during angiogenesis. So far, little is known about the specific localization of detyrosinated (detyr) and tyrosinated (tyr) tubulin in the placenta and its relevance for preeclampsia. METHODS: Placental expression of detyr- and tyr-tubulin was analyzed by immunohistochemistry, immunofluorescence and western blot. For western blot quantification we used biopsies from healthy placentas (n = 21) and placentas from pregnancies complicated with small for gestational age (n = 5), preeclampsia (n = 5) or both (n = 5). RESULTS: Specific placental localization of detyr-tubulin was detected in the fetal endothelial cells of the placenta. Villous and extravillous trophoblasts as well as villous stroma cells were tyr-tubulin positive. Detyr-tubulin protein expression was significantly decreased in placentas complicated by preeclampsia. CONCLUSIONS: In summary, we report an accumulation of detyr-tubulin in villous vessels of the placenta and a significantly reduced level of detyr-tubulin in placental biopsies of preeclampsia cases. The reduction of placental detyr-tubulin in preeclampsia could suggest a deficit in villous vascular plasticity and might be associated with the impaired arborization of the disease.
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Development and Validation of a Standardized Questionnaire and Standardized Diary for Use in Integrative Medicine Consultations in Gynecologic Oncology - Hack, Carolin; Huettner, N. B. M.; Fasching, Peter; Beckmann, Matthias (Geburtshilfe und Frauenheilkunde, 2015)
Introduction: Use of complementary and alternative medicine (CAM) in diagnoses is not standardized and is very heterogeneous. There are few published standards on integrative medicine consultations or CAM-specific validated follow-up questionnaires. The aim of this study was to develop a standard for integrative medicine consultations, a patient questionnaire which could be used as a basis for medical decisions, and a diary to evaluate the course of the integrative therapy. Patients and Methods: Between June 2013 and September 2014 a standardized integrative medicine consultation in gynecologic oncology was developed and implemented at the Department of Gynecology and Obstetrics of Erlangen University Hospital. A standard operating procedure for consultations was developed; the necessary instruments were developed and validated. Results: Overall patient assessment of the integrative medicine questionnaire and the integrative medicine diary with regard to the time required for completion, comprehensibility, complexity and functionality was positive. Patients evaluated the standardized overall concept of the integrative medicine consultation and its instruments as suitable. Conclusion: Our team is one of the first study groups to develop, validate and publish a standard procedure for integrative medicine consultations. In future, the standard operating procedure for integrative medicine procedures of the Department of Gynecology and Obstetrics of Erlangen University Hospital could be introduced in other hospitals and certified breast cancer centers and gynecologic cancer centers. This would offer patients maximum security and a standardized quality of care in integrative medicine.
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Development and validation of the gene-expression Predictor of high-grade-serous Ovarian carcinoma molecular subTYPE (PrOTYPE) - Talhouk, Aline; George, Joshy; Wang, Chen; Budden, Timothy; Tan, Tuan Zea; Chiu, Derek S.; Kommoss, Stefan; Leong, Huei San; Chen, Stephanie; Intermaggio, Maria P.; Gilks, Blake; Nazeran, Tayyebeh Mehrane; et al. (Clinical Cancer Research, 2020)
PURPOSE: Gene-expression-based molecular subtypes of high-grade serous tubo-ovarian cancer (HGSOC), demonstrated across multiple studies, may provide improved stratification for molecularly targeted trials. However, evaluation of clinical utility has been hindered by non-standardized methods which are not applicable in a clinical setting. We sought to generate a clinical-grade minimal gene-set assay for classification of individual tumor specimens into HGSOC subtypes and confirm previously reported subtype-associated features. EXPERIMENTAL DESIGN: Adopting two independent approaches, we derived and internally validated algorithms for subtype prediction using published gene-expression data from 1650 tumors. We applied resulting models to NanoString data on 3829 HGSOCs from the Ovarian Tumor Tissue Analysis Consortium. We further developed, confirmed, and validated a reduced, minimal gene-set predictor, with methods suitable for a single patient setting. RESULTS: Gene-expression data was used to derive the Predictor of high-grade-serous Ovarian carcinoma molecular subTYPE (PrOTYPE) assay. We established a de facto standard as a consensus of two parallel approaches. PrOTYPE subtypes are significantly associated with age, stage, residual disease, tumor infiltrating lymphocytes, and outcome. The locked-down clinical-grade PrOTYPE test includes a model with 55 genes that predicted gene-expression subtype with >95% accuracy that was maintained in all analytical and biological validations. CONCLUSIONS: We validated the PrOTYPE assay following the Institute of Medicine guidelines for the development of omics-based tests. This fully defined and locked-down clinical-grade assay will enable trial design with molecular subtype stratification and allow for objective assessment of the predictive value of HGSOC molecular subtypes in precision medicine applications.
CRIS-Team Scopus Importer:2020-06-30

Development of central nervous system metastases as a first site of metastatic disease in breast cancer patients treated in the neoadjuvant trials GeparQuinto and GeparSixto - Laakmann, Elena; Witzel, Isabel; Fasching, Peter; Rezai, Mandi; Schem, Christian; Solbach, Christine; Tesch, Hans; Klare, Peter; Schneeweiss, Andreas; Salat, Christoph; Zahm, Dirk-Michael; Blohmer, Jens-Uwe; et al. (Breast Cancer Research, 2019)
Background: The incidence of central nervous system (CNS) metastases in breast cancer patients is rising and has become a major clinical challenge. Only few data are published concerning risk factors for the development of CNS metastases as a first site of metastatic disease in breast cancer patients. Moreover, the incidence of CNS metastases after modern neoadjuvant treatment is not clear. Methods: We analyzed clinical factors associated with the occurrence of CNS metastases as the first site of metastatic disease in breast cancer patients after neoadjuvant treatment in the trials GeparQuinto and GeparSixto (n = 3160) where patients received targeted treatment in addition to taxane and anthracycline-based chemotherapy. Results: After a median follow-up of 61 months, 108 (3%) of a total of 3160 patients developed CNS metastases as the first site of recurrence and 411 (13%) patients had metastatic disease outside the CNS. Thirty-six patients (1%) developed both CNS metastases and other distant metastases as the first site of metastatic disease. Regarding subtypes of the primary tumor, 1% of luminal A-like (11/954), 2% of luminal B-like (7/381), 4% of HER2-positive (34/809), and 6% of triple-negative patients (56/1008) developed CNS metastases as the first site of metastatic disease. In multivariate analysis, risk factors for the development of CNS metastases were larger tumor size (cT3-4; HR 1.63, 95% CI 1.08-2.46, p = 0.021), node-positive disease (HR 2.57, 95% CI 1.64-4.04, p < 0.001), no pCR after neoadjuvant chemotherapy (HR 2.29, 95% CI 1.32-3.97, p = 0.003), and HER2-positive (HR 3.80, 95% CI 1.89-7.64, p < 0.001) or triple-negative subtype (HR 6.38, 95% CI 3.28-12.44, p < 0.001). Conclusions: Especially patients with HER2-positive and triple-negative tumors are at risk of developing CNS metastases despite effective systemic treatment. A better understanding of the underlying mechanisms is required in order to develop potential preventive strategies.
CRIS-Team Scopus Importer:2019-05-21
Keywords: Breast cancer; Central nervous system metastases; First site of metastatic disease

DGGG Guidelines Programme: Status Quo - Quo Vadis! - Beckmann, Matthias; Linde, I.; Buetof, C.; Kreienberg, R.; Gaß, Paul (Geburtshilfe und Frauenheilkunde, 2014)
The Guidelines programme of the German Society of Gynaecology and Obstetrics (DGGG) is an executive part of the DGGG Guidelines Commission. It includes in-house planning and organisation of all guidelines as well as representation outside of the DGGG. This article does not concern the development of the guidelines as much as it concerns the planning, organisation, registration, editing and publication of the guidelines in context of the DGGG Guidelines programme. It targets interested parties, especially authors and coordinators of guidelines.
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Diabetes and prognosis in a breast cancer cohort - Schrauder, Michael; Fasching, Peter A.; Häberle, Lothar; Lux, Michael P.; Rauh, Claudia; Hein, Alexander; Bayer, Christian M.; Heusinger, Katharina; Hartmann, Arndt; Strehl, Johanna D.; Wachter, David; Schulz-Wendtland, Rüdiger; et al. (Journal of Cancer Research and Clinical Oncology, 2011)
Purpose: Epidemiological studies indicated that type 2 diabetes mellitus may increase breast cancer risk and mortality. The aim of this retrospective cohort study was to examine the effect of diabetes on the clinical course and the prognosis of early stage breast cancer in relation to tumour and patient characteristics. Methods: The cohort analyzed in this study consisted of 4,056 patients with invasive primary breast cancer. We compared overall survival, distant metastasis-free survival and local recurrence free survival between breast cancer patients with and without diabetes. Results: In our cohort 276 breast cancer patients (6.8%) were affected by diabetes compared to 3,780 patients (93.2%) without diabetes. Women with diabetes were significantly older, had larger tumours, and a higher rate of lymph node involvement. After a follow-up period of 5 years, stratification for age and adjustment for other prognostic factors, overall mortality following breast cancer was significantly higher in diabetic breast cancer patients (hazard ratio, HR 1.92; 95% confidence interval, CI 1.49-2.48). We found no significant differences in distant metastasis-free survival and local recurrence free survival between the two groups, but we found a slightly significant higher rate of distant metastasis in the group of patients with diabetes and oestrogen receptor negative tumours (HR 2.28; CI 1.31-3.97). Conclusion: In this study, patients with diabetes and oestrogen receptor negative breast cancer had a more than 2-fold higher risk for distant metastasis compared to patients without diabetes. Diabetes was also associated with an almost 2-fold increase in mortality within the 5 years follow-up period. © 2010 Springer-Verlag.
CRIS-Team Scopus Importer:2021-07-19
Keywords: Breast cancer; Cohort study; Diabetes mellitus; Distant metastasis; Local recurrence; Survival

Diagnosis and Therapy before Assisted Reproductive TreatmentsGuideline of the DGGG, OEGGG and SGGG (S2k Level, AWMF Register Number 015-085, February 2019)-Part 1, Basic Assessment of the Woman - Toth, Bettina; Baston-Buest, Dunja Maria; Behre, Hermann M.; Bielfeld, Alexandra; Bohlmann, Michael; Buehling, Kai; Dittrich, Ralf; Goeckenjan, Maren; Hancke, Katharina; Kliesch, Sabine; Koehn, Frank-Michael; Kruessel, Jan; et al. (Geburtshilfe und Frauenheilkunde, 2019)
Introduction Supporting and counselling couples with fertility issues prior to starting ART is a multidisciplinary diagnostic and therapeutic challenge. The first German/Austrian/Swiss interdisciplinary S2k guideline on Diagnosis and Therapy Before Assisted Reproductive Treatments (ART) was published in February 2019. This guideline was developed in the context of the guidelines program of the German Society of Gynecology and Obstetrics (DGGG) in cooperation with the Swiss Society of Gynecology and Obstetrics (SGGG) and the Austrian Society of Gynecology and Obstetrics (OEGGG). Aims One third of the causes of involuntary childlessness are still unclear, even if the woman or man have numerous possible risk factors. Because the topic is still very much taboo, couples may be socially isolated and often only present quite late to a fertility center. At present, there is no standard treatment concept, as currently no standard multidisciplinary procedures exist for the diagnostic workup and treatment of infertility. The aim of this guideline is to provide physicians with evidence-based recommendations for counselling, diagnostic workup and treatment. Methods This S2k guideline was developed on behalf of the Guidelines Commission of the DGGG by representative members from different professional medical organizations and societies using a structured consensus process. Recommendations The first part of this guideline focuses on the basic assessment of affected women, including standard anatomical and endocrinological diagnostic procedures and examinations into any potential infections. Other areas addressed in this guideline are the immunological workup with an evaluation of the patient's vaccination status, an evaluation of psychological factors, and the collection of data relating to other relevant factors affecting infertility. The second part will focus on explanations of diagnostic procedures compiled in collaboration with specialists from other medical specialties such as andrologists, human geneticists and oncologists.
CRIS-Team Scopus Importer:2020-02-21
Keywords: endometriosis; guideline; infertility; PCOS; preconception counselling

Diagnosis and Therapy of Triple-Negative Breast Cancer (TNBC) - Recommendations for Daily Routine Practice - Schneeweiss, Andreas; Denkert, Carsten; Fasching, Peter; Fremd, Carlo; Gluz, Oleg; Kolberg-Liedtke, Cornelia; Loibl, Sibylle; Lück, Hans Joachim (Geburtshilfe und Frauenheilkunde, 2019)
The rapid increase in knowledge in tumour biology and tumour pathogenesis of triple-negative breast cancer (TNBC) has resulted in new therapeutic approaches and new therapeutic concepts for treatment. For years, TNBC has been considered to be a difficult-to-treat tumour due to its generally aggressive tumour biology and in view of limited therapeutic options. The risk of recurrence and metastasis is higher than in the case of other breast cancer subtypes of the same stage. In addition to surgery and radiation in the curative situation, systemic chemotherapy with anthracyclines and/or taxanes is still the therapy of choice. New therapeutic approaches are based on the knowledge that TNBC is a molecularly very heterogeneous disease. Research groups are working to classify TNBC better and better on a molecular level and use this molecular subtyping as the basis for new therapeutic strategies. The most promising new approaches and considerations regarding the therapy of TNBCs are shown below. In addition, the current therapeutic strategies are discussed using a fictitious case history, taking the current data and the resultant therapeutic consequence into account.
CRIS-Team Scopus Importer:2019-06-28
Keywords: BRCA mutation; diagnosis and therapy of TNBC; subtyping of TNBC; triple-negative breast cancer

Diagnosis and Treatment Before Assisted Reproductive Treatments. Guideline of the DGGG, OEGGG and SGGG (S2k Level, AWMF Register Number 015-085, February 2019) – Part 2, Hemostaseology, Andrology, Genetics and History of Malignant Disease - Toth, Bettina; Baston-Buest, Dunja Maria; Behre, Hermannm.; Bielfeld, Alexandra; Bohlmann, Michael; Buehling, Kai; Dittrich, Ralf; Goeckenjan, Maren; Hancke, Katharina; Kliesch, Sabine; Koehn, Frank-Michael; Kruessel, Jan; et al. (Geburtshilfe und Frauenheilkunde, 2019)
Introduction Supporting and counselling couples with fertility issues prior to starting ART is a multidisciplinary diagnostic and therapeutic challenge. The first German-language interdisciplinary S2k guideline on Diagnosis and Therapy Before Assisted Reproductive Treatments (ART) was published in February 2019. The guideline was developed in the context of the guidelines program of the German Society of Gynecology and Obstetrics (DGGG) in cooperation with the Swiss Society of Gynecology and Obstetrics (SGGG) and the Austrian Society of Gynecology and Obstetrics (OEGGG). Aim In one third of cases, the cause of involuntary childlessness remains unclear, even if the woman or man have numerous possible risk factors. Because the topic is still very much taboo, couples may be socially isolated and often only present quite late to a fertility center. There is no standard treatment concept for these patients at present, as there are currently no standard multidisciplinary procedures for the diagnostic workup and treatment of infertility. The aim of this guideline is to provide physicians with evidence-based recommendations for counselling, diagnosis and treatment. Methods This S2k guideline was developed on behalf of the Guidelines Commission of the DGGG by representative members from different professional medical organizations and societies using a structured consensus process. Recommendations This second part of the guideline describes the hematological workup for women as well as additional diagnostic procedures which can be used to investigate couples and which are carried out in cooperation with physicians working in other medical fields such as andrologists, geneticists and oncologists.
CRIS-Team Scopus Importer:2020-02-21
Keywords: andrology; genetics; guideline; infertility; oncology; preconception counselling

Diagnosis and Treatment of Endometriosis. Guideline of the DGGG, SGGG and OEGGG (S2k Level, AWMF Registry Number 015/045, August 2020) - Burghaus, Stefanie; Schäfer, Sebastian D.; Beckmann, Matthias; Brandes, Iris; Brünahl, Christian; Chvatal, Radek; Drahoå ovský, Jan; Dudek, Wojciech; Ebert, Andreas D.; Fahlbusch, Christine; Fehm, Tanja; Fehr, Peter Martin; et al. (Geburtshilfe und Frauenheilkunde, 2021)
Aims The aim of this official guideline published and coordinated by the German Society of Gynaecology and Obstetrics (DGGG) in cooperation with the Austrian Society for Gynaecology and Obstetrics (OEGGG) and the Swiss Society for Gynaecology and Obstetrics (SGGG) was to provide consensus-based recommendations for the diagnosis and treatment of endometriosis based on an evaluation of the relevant literature. Methods This S2k guideline represents the structured consensus of a representative panel of experts with different professional backgrounds commissioned by the Guideline Committee of the DGGG, OEGGG and SGGG. Recommendations Recommendations on the epidemiology, aetiology, classification, symptomatology, diagnosis and treatment of endometriosis are given and special situations are discussed.
CRIS-Team Scopus Importer:2021-04-23
Keywords: diagnosis; endometriosis; guideline; pelvic pain; treatment

Diagnosis, Therapy and Follow-up of Cervical Cancer. Guideline of the DGGG, DKG and DKH (S3-Level, AWMF Registry No. 032/033OL, May 2021) – Part 1 with Recommendations on Epidemiology, Screening, Diagnostics and Therapy - Beckmann, Matthias; Stübs, Frederik; Koch, Martin; Mallmann, Peter; Dannecker, Christian; Dietl, Anna; Sevnina, Anna; Mergel, Franziska; Lotz, Laura; Hack, Carolin; Ehret, Anne; Gantert, Daniel; et al. (Geburtshilfe und Frauenheilkunde, 2022)
Aim This update of the interdisciplinary S3 guideline on the Diagnosis, Therapy and Follow-up of Cervical Cancer (AWMF Registry No. 032/033OL) was published in March 2021. This updated guideline was funded by German Cancer Aid (Deutsche Krebshilfe) as part of the German Guideline Program in Oncology. The guideline was coordinated by the German Society of Gynecology and Obstetrics (Deutsche Gesellschaft für Gynäkologie und Geburtshilfe, DGGG) and the Working Group on Gynecological Oncology (Arbeitsgemeinschaft Gynäkologische Onkologie, AGO) of the German Cancer Society (Deutsche Krebsgesellschaft, DKG). Method The process of updating the S3 guideline dating from 2014 was based on an appraisal of the available evidence using the criteria of evidence-based medicine, adaptations of existing evidence-based national and international guidelines or - if evidence was lacking - on a consensus of the specialists involved in compiling the update. After an initial review of the current literature was carried out according to a prescribed algorithm, several areas were identified which, in contrast to the predecessor version from September 2014, required new recommendations or statements which took account of more recently published literature and the appraisal of the new evidence. Recommendations The short version of this guideline consists of recommendations and statements on the epidemiology, screening, diagnostic workup and therapy of patients with cervical cancer. The most important new aspects included in this updated guideline include the newly published FIGO classification of 2018, the radical open surgery approach for cervical cancers up to FIGO stage IB1, and use of the sentinel lymph node technique for tumors ≤ 2 cm. Other changes include the use of PET-CT, new options in radiotherapy (e.g., intensity-modulated radiotherapy, image-guided adaptive brachytherapy), and drug therapies to treat recurrence or metastasis.
CRIS-Team Scopus Importer:2022-03-04
Keywords: cervical cancer; cervical intraepithelial neoplasia; follow-up; guideline; therapy

Diagnosis, Therapy and Follow-up of Cervical Cancer. Guideline of the DGGG, DKG and DKH (S3-Level, AWMF Registry No. 032/033OL, May 2021) – Part 2 with Recommendations on Psycho-oncology, Rehabilitation, Follow-up, Recurrence, Palliative Therapy and Healthcare Facilities - Fehm, Tanja; Stübs, Frederik; Koch, Martin; Mallmann, Peter; Dannecker, Christian; Dietl, Anna; Sevnina, Anna; Mergel, Franziska; Lotz, Laura; Hack, Carolin; Ehret, Anne; Gantert, Daniel; et al. (Geburtshilfe und Frauenheilkunde, 2022)
Aim This is an update of the interdisciplinary S3-guideline on the Diagnosis, Therapy and Follow-up of Cervical Cancer (AWMF Registry No. 032/033OL), published in March 2021. The work on the updated guideline was funded by German Cancer Aid (Deutsche Krebshilfe) as part of the German Guideline Program in Oncology. The guideline was coordinated by the German Society of Gynecology and Obstetrics (Deutsche Gesellschaft für Gynäkologie und Geburtshilfe, DGGG) and the Working Group on Gynecological Oncology (Arbeitsgemeinschaft Gynäkologische Onkologie, AGO) of the German Cancer Society (Deutsche Krebsgesellschaft, DKG). Method The process used to update the 2014 S3-guideline was based on an appraisal of the available evidence using the criteria of evidence-based medicine, adaptations of existing evidence-based national and international guidelines or - if evidence was lacking - on the consensus of the specialists involved in compiling the update. After an initial review of the current literature was carried out according to a prescribed algorithm, several areas were identified which, in contrast to the predecessor version from September 2014, required new recommendations or statements which would take account of more recently published literature and the recent appraisal of new evidence. Recommendations The short version of this guideline consists of recommendations and statements on palliative therapy and follow-up of patients with cervical cancer. The most important aspects included in this updated guideline are the new FIGO classification published in 2018, the radical open surgery approach used to treat cervical cancer up to FIGO stage IB1, and the use of the sentinel lymph node technique for tumors ≤ 2 cm. Other changes include the use of PET-CT, new options in radiotherapy (e.g., intensity-modulated radiotherapy, image-guided adaptive brachytherapy), and drug therapies to treat recurrence or metastasis.
CRIS-Team Scopus Importer:2022-02-25
Keywords: cervical cancer; cervical intraepithelial neoplasia; follow-up; guideline; therapy

Diagnosis, Therapy and Follow-up of Vaginal Cancer and Its Precursors. Guideline of the DGGG and the DKG (S2k-Level, AWMF Registry No. 032/042, October 2018) - Schnürch, Hans Georg; Ackermann, Sven; Alt-Radtke, Celine D.; Angleitner, Lukas; Barinoff, Jana; Beckmann, Matthias; Böing, Carsten; Dannecker, Christian; Fehm, Tanja; Gaase, Rüdiger; Gaß, Paul; Gebhardt, Marion; et al. (Geburtshilfe und Frauenheilkunde, 2019)
Purpose This is an official guideline, published and coordinated by the Gynecological Oncology Working Group (AGO) of the German Cancer Society (DKG) and the German Society for Gynecology and Obstetrics (DGGG). Vaginal cancers are rare tumors, which is why there is very little evidence on these tumors. Knowledge about the optimal clinical management is limited. This first German S2k guideline on vaginal cancer has aimed to compile the most current expert knowledge and offer new recommendations on the appropriate treatment as well as providing pointers about individually adapted therapies with lower morbidity rates than were previously generally available. The purpose of this guideline is also to set up a register to record data on treatment data and the course of disease as a means of obtaining evidence in future. Methods The present S2k guideline was developed by members of the Vulvar und Vaginal Tumors Commission of the AGO in an independently moderated, structured, formal consensus process and the contents were agreed with the mandate holders of the participating scientific societies and organizations. Recommendations To optimize the daily care of patients with vaginal cancer: 1. Monitor the spread pattern; 2. Follow the step-by-step diagnostic workup based on initial stage at detection; 3. As part of individualized clinical therapeutic management of vaginal cancer, follow the sentinel lymph node protocol described here, where possible; 4. Participate in the register study on vaginal cancer.
CRIS-Team Scopus Importer:2019-11-05
Keywords: sentinel lymph node biopsy; vaginal cancer; VaIN

Diagnostic Accuracy of Breast Medical Tactile Examiners (MTEs): A Prospective Pilot Study - Lux, Michael P.; Emons, Julius; Bani, Mayada; Wunderle, Marius; Sell, Charlotte; Preuss, Caroline; Rauh, Claudia; Jud, Sebastian; Heindl, Felix; Langemann, Hanna; Geyer, Thomas; Brandl, Anna-Lisa; et al. (Breast Care, 2019)
Background: The usefulness of clinical breast examination (CBE) in general and in breast cancer screening programs has been a matter of debate. This study investigated whether adding vision-impaired medical tactile examiners (MTEs) improves the predictiveness of CBE for suspicious lesions and analyzed the feasibility and acceptability of this approach. Methods: The prospective study included 104 patients. Physicians and MTEs performed CBEs, and mammography and ultrasound results were used as the gold standard. Sensitivity and specificity were calculated and logistic regression models were used to compare the predictive value of CBE by physicians alone, MTEs alone, and physicians and MTEs combined. Results: For CBEs by physicians alone, MTEs alone, and both combined, sensitivity was 71, 82, and 89% and specificity was 55, 45, and 35%, respectively. Using adjusted logistic regression models, the validated areas under the curve were 0.685, 0.692, and 0.710 (median bootstrapped p value (DeLong) = 0.381). Conclusion: The predictive value for a suspicious breast lesion in CBEs performed by MTEs in patients without prior surgery was similar to that of physician-conducted CBEs. Including MTEs in the CBE procedure in breast units thus appears feasible and could be a way of utilizing their skills. (c) 2019 S. Karger AG, Basel
CRIS-Team WoS Importer:2019-03-22

Diagnostic impact of ascites cytology in 941 patients: malignancy rates and time of detection in ovarian cancer relative to other tumor types - Krugmann, Jens; Schwarz, Corinna Lang; Melcher, Balint; Sterlacci, William; Rösch, Sophia; Lermann, Johannes; Vieth, Michael (Archives of Gynecology and Obstetrics, 2020)
Background: Cytological analysis of ascitic fluid is an important tool for diagnosis, staging, and prognostic assessment in patients with cancer, but more detailed information is needed regarding malignancy rates and the time sequence in which ascites develops for different sites of cancer origin. Especially, an increased early tumor diagnosis may improve the acceptance for cytological examinations for the tumor patients in oncological practice. Methods: Ascites specimens from patients who were treated at Bayreuth Hospital from 2006 to 2015 were reevaluated retrospectively and correlated with clinical reports. Results: 580 of all 941 ascitis specimens (61.6%) were from patients with malignancies with predominant appearance of gastrointestinal and gynecological tumors in 516/580 (89%) patients. Histologically, 549 (94.6%) were carcinomas, 23 (4%) hematological malignancies, 5 (0.9%) mesotheliomas and 3 (0.5%) were melanomas. Malignant ascitic fluid was noted in 298 of the 580 (51.4%) patients with cancer, thus the overall malignancy rate in the ascites specimens examined was 298/941 (31.7%). The most frequent malignancy rate for gynecological tumors we obtained in ovarian cancer with 85.7% and in the upper gastrointestinal tract with 77.8% for Barrett’s carcinoma and 61,4% for gastric carcinoma. Regarding time of detection, malignant ascitic fluid was noted as a separate finding, prior or simultaneous to the histological diagnosis of cancer in 225/298 patients (75.5%). An outstanding earliest occurrence was found in ovarian carcinoma in 94.9% and in the gastrointestinal tract in pancreatic carcinoma in 66.7%. Conclusions: Tumor staging was the main important clinical question in our single center study of ascitic fluid, especially for patients with gastrointestinal and gynecological malignomas. The highest malignancy rate and earliest time of tumor detection caused the leading importance for ovarian tumors in malignant ascitic fluid. Moreover, the application of immunostains in our study allowed in 75.5% of all tumor patients a correct initial diagnosis, which is important for further clinical therapy.
CRIS-Team Scopus Importer:2020-05-08
Keywords: Malignancy rates; Malignant ascites; Neoplasia; Time of detection

Did you drink alcohol during pregnancy? Inaccuracy and discontinuity of women's self-reports: On the way to establish meconium ethyl glucuronide (EtG) as a biomarker for alcohol consumption during pregnancy - Eichler, Anna; Grunitz, Juliane; Grimm, Jennifer; Walz, Lisa; Raabe, Eva; Goecke, Tamme W.; Beckmann, Matthias; Kratz, Oliver; Heinrich, Hartmut; Moll, Gunther; Fasching, Peter; Kornhuber, Johannes (Alcohol, 2016)
Consuming alcohol during pregnancy is one of the most verified prenatal risk factors for impaired child development. Information about the amount of alcohol consumed prenatally is needed to anticipate negative effects and to offer timely support. Women's self-reports are not reliable, often influenced by social stigmas and retrospective recall bias, causing biomarkers of intrauterine ethanol exposure to become more and more relevant. The present study compares both women's gestational and retrospective self-reports of prenatal alcohol consumption with levels of ethyl glucuronide (EtG) in meconium. Women (n = 180) gave self-reports of prenatal alcohol consumption both during their 3rd trimester (gestational self-report) and when their children were 6-8 years old (retrospective self-report). Child meconium was collected after birth and analyzed for EtG. No individual feedback of children's EtG level was given to the women. All analyses were run separately for two cut-offs: 10 ng/g (limit of detection) and 120 ng/g (established by Goecke et al., 2014). Mothers of children with EtG values above 10 ng/g (n = 42) tended to report prenatal alcohol consumption more frequently. There was no trend or significance for the EtG cut-off of 120 ng/g (n = 26) or for retrospective self-report. When focusing on women who retrospectively reported alcohol consumption during pregnancy, a claim to five or more consumed glasses per month made an EtG over the 10 ng/g and the 120 ng/g cut-off more probable. Women whose children were over the 10 ng/g EtG cut-off were the most inconsistent in their self-report behavior, whereas the consistency in the above 120 ng/g EtG group was higher than in any other group. The next step to establish EtG as a biomarker for intrauterine alcohol exposure is to correlate EtG values in meconium with child developmental impairments.
EVALuna2:23752

Die Arbeits- und Weiterbildungssituation junger Ärztinnen und Ärzte in Deutschland – eine zusammenfassende Analyse von Befragungsergebnissen aus sechs Fachrichtungen - Joachim, Stephanie C.; Bitzinger, Diane; Arnold, Hannah; Lermann, Johannes; Oechtering, Thekla H.; Schott, Sarah; Schulte, Kevin; Raspe, Matthias (Gesundheitswesen, 2020)
Objective The working and training conditions of young physicians in Germany have changed over the last few years, as a result of far-reaching changes in the healthcare system. Therefore, Germany-wide surveys among young physicians of several disciplines were evaluated in a pooled analysis, in order to obtain a current interdisciplinary impression of conflicts in their daily work. Material and methods Data from web-based surveys from residents training in six disciplines were analyzed together retrospectively. One focus was a gratification crises model for the assessment of psychosocial workload. Results Data on 4041 participants were evaluated. In day-to-day work, young physicians were burdened with a high proportion of tasks that were not directly medical. Instruments of good subspecialty training, such as training contracts, curricula and regular feedback were associated with a lower psychosocial workload, which was generally significant among the participants. An economic influence on medical-professional decisions was subjectively clearly present among the participants. Conclusion Many young doctors find the current work and training conditions in the medical work environment unsatisfactory. This might have consequences not only for the doctors themselves, but also for the patients they care for. A healthy work environment with health professionals in good health is therefore crucial and should be in everyone's interest.
CRIS-Team Scopus Importer:2020-04-17
Keywords: economic influence; gratification crisis; psychosocial workstrain; specialty training; working conditions; young physician

Die Bedeutung mütterlicher präpartaler Depression und Mutter-Kind-Bindung für die Entwicklung der kindlichen Emotionsregulation: Erste Befunde einer Längsschnittstudie - Ziegler, Clara; Zalan, Vera; Eichler, Anna; Heinrich, Hartmut; Moll, Gunther; Fasching, Peter; Beckmann, Matthias; Kornhuber, Johannes; Lenz, Bernd; Spangler, Gottfried (50. Jahreskongress der Deutschen Gesellschaft für Psychologie, 2016)

Differential effect on different immune subsets of neoadjuvant chemotherapy in patients with TNBC - Massa, Chiara; Karn, Thomas; Denkert, Carsten; Schneeweiss, Andreas; Hanusch, Claus; Blohmer, Jens Uwe; Zahm, Dirk Michael; Jackisch, Christian; Van Mackelenbergh, Marion; Thomalla, Jörg; Marme, Frederik; Huober, Jens; et al. (Journal for ImmunoTherapy of Cancer, 2020)
Background Triple-negative breast cancer (TNBC) is the most aggressive form of breast cancer (BC). Due to the absence of targets such as HER2 or hormone receptors, early TNBC is treated with surgery and chemotherapy. Since TNBC is also considered the most immunogenic type of BC with tumor infiltrating lymphocytes that are predictive for chemotherapy response and prognostic for patients′ survival, many different immunotherapeutic strategies are currently explored in clinical trials for the treatment of this disease. In order to efficiently combine chemotherapy with immunotherapy, it is important to evaluate the effect of chemotherapy on immune cells in vivo. Methods Peripheral blood was taken from 56 patients with TNBC undergoing neoadjuvant chemotherapy with nanoparticle albumin-bound paclitaxel (Nab-Pac) followed by epirubicin and cyclophosphamide (EC) at three different time points. Multicolor flow cytometry was used to characterize the immune cell composition and functional properties along neoadjuvant chemotherapy. Results Whereas the first phase of the neoadjuvant chemotherapy did not significantly alter the patients′ immune cell composition, after the second phase of chemotherapeutic administration most B cells (>90%) were lost and the frequency of natural killer (NK) cells and CD4 + T lymphocytes decreased approximately to 50%. In contrast, the frequency of CD8 + T cells were less affected. Conclusions Despite late consequences of Nab-Pac cannot be ruled out, these data suggest that different chemotherapeutics might have distinct effects on the immune cell repertoire and that different immune cell populations exhibit a specific susceptibility to these chemotherapies with B and NK cells being more affected than T cells. This might also have an impact on the combination of chemotherapies with immunotherapies. Trial registration number NCT02685059.
CRIS-Team Scopus Importer:2020-11-27
Keywords: breast neoplasms; immunocompetence

Differential effects of low birthweight and intrauterine growth restriction on umbilical cord blood insulin-like growth factor concentrations - Tzschoppe, Anja; Riedel, Christina; Von Kries, Ruediger; Struwe, Ellen; Rascher, Wolfgang; Dörr, Helmuth-Günther; Beckmann, Matthias; Schild, Ralf L.; Goecke, Tamme W.; Flyvbjerg, Allan; Frystyk, Jan; Doetsch, Joerg (Clinical Endocrinology, 2015)
Alterations in the growth hormone-insulin-like growth factor (IGF) axis have been considered as a causal factor for intrauterine growth restriction (IUGR) and for the increased risk of metabolic disease in later life. We compared members of the IGF axis in umbilical cord blood between IUGR neonates, small for gestational age without foetal restriction (SGA) and appropriate for gestational age (AGA) neonates.Prospective controlled multicenter study.Sixteen ultrasound-proven IUGR, 8 SGA and 40 AGA neonates.Concentrations of total IGF-I and total IGF-II by immunoassays, bioactive IGF by cell-based bioassay and IGFBP-I in mixed venous and arterial umbilical cord blood samples at birth. Auxological parameters at birth.IGF-I concentrations in IUGR [17·7 ?g/l (CI 13·8;21·6)] were clearly below those in AGA [48·3 ?g/l (CI 43·7;52·9)] and SGA neonates [36·0 ?g/l (CI 26·6;45·4)]. IGF-II levels were significantly reduced in IUGR [201·4 ?g/l (CI 190·2;212·6)] compared to AGA neonates [231·2 ?g/l (CI 220·6;241·9)]. A trend for lower IGF-II concentrations was observed in IUGR when compared to SGA neonates [232·0 ?g/l (CI 207·2;256·8)]. These differences could not be explained by confounding. For IGFBP-1, a trend towards higher values in IUGR was observed.Low IGF-I cord blood concentrations in hypotrophic neonates after IUGR might not only result from low birthweight per se, but also reflect prenatal placental environment. Alterations of the IGF axis could be in the causal pathway of IUGR and thus constitute a potential surrogate marker for IUGR in the assessment of foetal programming.
EVALuna2:17440

Differential prognostic relevance of patho-anatomical factors among different tumor-biological subsets of breast cancer: Results from the adjuvant SUCCESS A study - Deniz, Miriam; Degregorio, Amelie; Degregorio, Nikolaus; Bekes, Inga; Widschwendter, Peter; Schochter, Fabienne; Ernst, Kristina; Scholz, Christoph; Bauer, Emanuel C. A.; Aivazova-Fuchs, Viktoria; Weissenbacher, Tobias; Kost, Bernd; et al. (BREAST, 2019)
Objectives: In breast cancer, large tumor size, positive nodal stage and a triple-negative tumor subtype are associated with reduced survival, but the interactions between these prognostic factors are not well understood.
CRIS-Team WoS Importer:2019-03-20

DIFFERENT NUTRIENT INTAKE AND PREVALENCE OF GASTROINTESTINAL COMORBIDITIES IN WOMEN WITH ENDOMETRIOSIS - Schink, Monic; Konturek, P. C.; Herbert, S. L.; Renner, S. P.; Burghaus, Stefanie; Blum, Simon; Fasching, Peter; Neurath, Markus; Zopf, Yurdagül (Journal of Physiology and Pharmacology, 2019)
Even though endometriosis presents one of the most common gynaecological diseases, the pathogenesis is insufficiently studied. Besides immunologic, inflammatory or oxidative processes, recent studies also suggest an influence of nutrition on disease onset and progression. Because data about the actual nutrient intake of endometriosis patients are scarce, we aimed to examine the actual nutrient intake and potential influencing factors in these women. A total of 156 women with endometriosis (EM) and 52 age-matched controls were included in this retrospective case-control study. All women filled in a validated food frequency questionnaire to acquire the nutrient intake of the past 12 months and a disease-related questionnaire for the determination of disease status, clinical symptoms and comorbidities. Patients with endometriosis suffered significantly more from diet-related comorbidities like food intolerances (25.6% versus 7.7%; P = 0.009) and allergies (57% versus 31%; P < 0.001) compared to controls. Also gastrointestinal symptoms, including constipation, flatulence, pyrosis, diarrhea or frequent defecation, were higher in the EM group (77% versus 29%; P < 0.001). The nutrient intake of patients with endometriosis differed significantly compared to controls with a significantly lower ingestion of organic acids (P = 0.006), maltose (P = 0.0.16), glycogen (P = 0.035), tetradecenoic acid (P = 0.041), methionine (P = 0.046), lysine (P = 0.048), threonine (P = 0.046) and histidine (P = 0.049). The total intake of animal proteins was significantly lower in the EM group compared to the controls (P = 0.047). EM patients showed a decreased intake of vitamin C (P = 0.031), vitamin B-12 (P = 0.008) and magnesium (P = 0.043) compared to controls. This study confirms a high association of endometriosis and gastrointestinal disorders accompanied by an altered nutrient intake. A dietary intervention by a professional nutritionist may help to reduce disease burden in the affected women.
CRIS-Team WoS Importer:2019-10-18

Digitalization is not everything but everything is nothing without digitalization Digitalisierung ist nicht alles, aber alles ist nichts ohne Digitalisierung - Kiechle, Marion; Wallwiener, Stephanie; Wagner, Uwe; Fasching, Peter (Die Gynäkologie, 2024)
CRIS-Team Scopus Importer:2025-02-04

Digital Maternity Records: Motivation, Acceptance, Requirements, Usability and Prototype Evaluation of an Interface for Physicians and Midwives - Dörflinger, Luisa; Nissen, Michael; Jäger, Katharina; Wirth, Markus; Titzmann, Adriana; Pontones, Constanza; Fasching, Peter; Beckmann, Matthias; Gradl, Stefan; Eskofier, Björn (Mensch und Computer 2021, 2021)
Maternity records (”Mutterpass”) are a central tool in Germany’s antenatal care. Its digitalisation offers advantages such as improved readability, data standardisation, analysability, digital assistance and the avoidance of media breaks. Despite the examined necessity and technical possibility, no system has been implemented yet. In this work, we address this gap by assessing physicians’ and midwives’ perception, motivation, acceptance and requirements of a digital maternity record and its user interface in particular. Nine medical professionals participated in semi-structured interviews. Based on the results, an interface prototype was subsequently developed. The prototype laid a particular focus on two different gravidogram implementations. Thirteen medical professionals participated in the interactive user interface study, which aimed to assess general acceptance, completion time, error rate and implemented assistance functions compared to the analogue counterpart. Results show that the implementation of the digital maternity logbook is of value and that its advantages are both accepted and demanded by medical professionals. Eight key requirements were identified. A tabular gravidogram prototype, inspired by the analogue maternity record, was favoured over a more novel list prototype. Users presented a clear learning curve of the digital system. Nevertheless, the digital average completion time is 30% higher than its analogue counterpart. The digital prototype lead to a lower average number of errors per entry (0.45±0.3 vs. 0.58±0.4). With respect to digital maternity records, this work underlines user acceptance, summarizes key user requirements and presents a first step on the path to a digital maternity record interface for medical professionals. On a broader scale, it delivers insights based on several metrics with respect to digitalisation in an area that is still highly dominated by long established paper-based tools.

Digit ratio (2D:4D) and behavioral symptoms in primary-school aged boys - Eichler, Anna; Heinrich, Hartmut; Moll, Gunther; Beckmann, Matthias; Goecke, Tamme W.; Fasching, Peter; Muschler, Marcel-Rene; Bouna-Pyrrou, Polyxeni; Lenz, Bernd; Kornhuber, Johannes (Early Human Development, 2018)
The second-to-forth digit length ratio (2D:4D) is considered to be a biomarker for intrauterine androgen levels. It is associated with adult and child mental health problems, primarily with behavioral symptoms and predominantly in males. Using a cross-sectional design, we examined whether 2D:4D was associated with conduct disorder (CD) symptoms in 138 primary-school aged children (54% boys, Mage = 7.70 years) and considered child sex as a moderating factor. Children's digit lengths were measured from hand scans and mothers rated the behavioral/emotional symptoms of their child. The regression analyses revealed that 2D:4D ratios were associated with behavioral symptoms in boys (β = -0.260, p = 0.026), but not in girls (β = -0.040, p = 0.762). Child emotional symptoms, analyzed as a control, were not significantly correlated with 2D:4D. In conclusion, prenatal brain hyperandrogenization - operationalized by the 2D:4D biomarker - could result in behavioral symptoms in boys at early school age, reflecting one predictor for early onset CD. Our data support the use of 2D:4D as a marker of prenatal androgen exposure.
EVALuna2:36369

Discordance between Primary Breast Cancer and Ipsilateral Breast Cancer Tumor Recurrence as a Function of Distance - Jud, Sebastian; Hatko, Reinhard; Emons, Julius; Lauterbach, Bianca; Hack, Carolin; Preuss, Caroline; Adler, Werner; Beckmann, Matthias; Heindl, Felix (Journal of Clinical Medicine, 2020)
Background: Risk factors for ipsilateral breast cancer tumor recurrence (IBTR) are well established and include grading, nodal status, and receptor status. Little is known about the influence of the local distance between the primary tumor and recurrences on changes in tumor characteristics and prognosis. Methods: In a retrospective setting, we analyzed primary breast cancers and their recurrences. Localizations of primary and recurrent breast cancer were recorded to calculate the relative distance in pixels. Analysis was performed regarding tumor characteristics, relative distance between both, and their impact on breast cancer prognosis. Results: In a cohort of 142 patients with ipsilateral recurrence, no statistically significant difference could be shown in the change in tumor characteristics depending on distance. Progesterone receptor (PR) and estrogene receptor (ER) status changed in 22.7% and 14.9% of cases, respectively. human epidermal growth factor receptor 2 (ERBB2, HER2) status changed in 18.3% of cases. Survival was in accordance with the literature, with luminal-A-like tumors as best and triple negative breast cancers (TNBC) as worst prognosis. With a threshold of 162 pixels, the survival was significantly better in the group with shorter distance. Conclusion: Change in tumor characteristics from primary breast cancer to recurrence occurs more often in PR than ER. In contrast to other work, in this dataset, recurrences with a larger distance to the primary tumor had a worse prognosis in univariate analysis. A Cox model might indicate the possibility that this influence is independent of other risk factors.
CRIS-Team WoS Importer:2021-01-15

Discourse Is Research at German University Clinics still desirable, possible and effective? - Summary of the Discussion Forum at the 61st DGGG-Congress 2016 in Stuttgart - Puppe, Julian; Schott, Sarah; Eismann, Sabine; Tzschaschel, Marie; Rody, Achim; Woeckel, Achim; Lermann, Johannes; Gabriel, Lena; Beckmann, Matthias; Gaß, Paul (Geburtshilfe und Frauenheilkunde, 2017)
EVALuna2:36135

Discrimination analysis of breast calcifications using x-ray dark-field radiography - Rauch, Thomas; Rieger, Jens; Pelzer, Georg; Horn, Florian; Erber, Ramona; Wunderle, Marius; Emons, Julius; Nabieva, Naiba; Fuhrich, Nicole; Michel, Thilo; Hartmann, Arndt; Fasching, Peter; et al. (Medical Physics, 2020)
Background X-ray dark-field radiography could enhance mammography by providing more information on imaged tissue and microcalcifications. The dark field signal is a measure of small angle scattering and can thus provide additional information on the imaged materials. This information can be useful for material distinction of calcifications and the diagnosis of breast cancer by classifying benign and malign association of these calcifications.
CRIS-Team WoS Importer:2020-03-06

Discussion of ABC7 Consensus and German Recommendations - Untch, Michael; Ditsch, Nina; Fasching, Peter; Busch, Steffi; Ettl, Johannes; Haidinger, Renate; Harbeck, Nadia; Jackisch, Christian; Lüftner, Diana; Müller, Lothar; Ruckhäberle, Eugen; Schumacher-Wulf, Eva; et al. (Geburtshilfe und Frauenheilkunde, 2024)
The rationale behind the International Consensus Conference for Advanced Breast Cancer (ABC) is to standardize the treatment of patients with advanced or metastatic breast cancer worldwide using an evidence-based approach. The aim is also to ensure that patients in all countries receive adequate treatment based on current treatment recommendations and standards. The 7th International Consensus Conference on Advanced Breast Cancer (ABC7) took place from November 9 to 12, 2023 in Lisbon/Portugal. ABC7 focused on metastatic disease as well as on locally advanced and inflammatory breast cancer. Special topics included the treatment of oligometastatic patients, leptomeningeal disease, treatment of brain metastases, and pregnant women with ABC. As in previous years, patient advocates from all over the world participated in the consensus conference and were involved in decision making.
CRIS-Team Scopus Importer:2024-06-14
Keywords: ABC and pregnancy; ADCs; brain metastases; leptomeningeal disease; oligometastases; systemic therapy

Disease-free survival as a surrogate for overall survival in HR+/HER2– early breast cancer: A correlation analysis - Untch, Michael; Pérol, David; Mayer, Erica L.; Cortes, Javier; Nusch, Arnd; Cameron, David; Barrios, Carlos; Delea, Thomas; Danyliv, Andrii; Mishra, Namita; Gupta, Rhea; Pathak, Purnima; et al. (European Journal of Cancer, 2024)
Background: Overall survival (OS) is a universally accepted measure of clinical benefit; however, prolonged follow-up is needed to observe sufficient events. Disease-free survival (DFS) has been widely adopted as a primary endpoint for early breast cancer (EBC) trials, as follow-up is comparatively shorter. Here, we present an analysis evaluating DFS as a surrogate for OS for adjuvant treatment of hormone receptor–positive/human epidermal growth factor receptor 2–negative (HR+/HER2–) EBC. Methods: A systematic literature review which included randomized controlled trials (RCTs) with ≥80% of adult patients with HR+/HER2– EBC was conducted. The RCTs evaluated various systemic therapeutic categories; key inclusion criteria included reporting of DFS and OS hazard ratios (HRs) and mature OS data. Spearman rank correlation and weighted linear regression analyses evaluated DFS and OS HR correlation. A scenario analysis tested base-case analysis robustness, and a parallel analysis using patient-level data was conducted. Results: The base case (N = 14 RCTs) showed an unweighted Spearman coefficient of 0.81 between OS and DFS (weighted: 0.81), with 84% of the variability in OS explained by DFS differences (R2 from weighted regression). The surrogate threshold effect (Burzykowski T, Buyse M. Pharm Stat. 2006;5:173–186) was 0.82 for DFS/OS HR. Scenario analysis (n = 9 RCTs), which excluded chemotherapy trials, and patient-level analysis using FACE trial data were consistent with the base-case analysis. Conclusions: These analyses support DFS as a reliable surrogate endpoint for OS in adjuvant HR+/HER2− EBC trials. Using DFS as a surrogate measure will permit timelier access to novel treatments for patients with HR+/HER2− EBC.
CRIS-Team Scopus Importer:2024-03-22
Keywords: Disease-free survival; HR+/HER2– early breast cancer; Overall survival; Surrogate endpoint

Disentangling the relationships of body mass index and circulating sex hormone concentrations in mammographic density using Mendelian randomization - Haas, Cameron B.; Chen, Hongjie; Harrison, Tabitha; Fan, Shaoqi; Gago-Dominguez, Manuela; Castelao, Jose E.; Bolla, Manjeet K.; Wang, Qin; Dennis, Joe; Michailidou, Kyriaki; Dunning, Alison M.; Easton, Douglas F.; et al. (Breast Cancer Research and Treatment, 2024)
Purpose: Mammographic density phenotypes, adjusted for age and body mass index (BMI), are strong predictors of breast cancer risk. BMI is associated with mammographic density measures, but the role of circulating sex hormone concentrations is less clear. We investigated the relationship between BMI, circulating sex hormone concentrations, and mammographic density phenotypes using Mendelian randomization (MR). Methods: We applied two-sample MR approaches to assess the association between genetically predicted circulating concentrations of sex hormones [estradiol, testosterone, sex hormone-binding globulin (SHBG)], BMI, and mammographic density phenotypes (dense and non-dense area). We created instrumental variables from large European ancestry-based genome-wide association studies and applied estimates to mammographic density phenotypes in up to 14,000 women of European ancestry. We performed analyses overall and by menopausal status. Results: Genetically predicted BMI was positively associated with non-dense area (IVW: β = 1.79; 95% CI = 1.58, 2.00; p = 9.57 × 10−63) and inversely associated with dense area (IVW: β = − 0.37; 95% CI = − 0.51,− 0.23; p = 4.7 × 10−7). We observed weak evidence for an association of circulating sex hormone concentrations with mammographic density phenotypes, specifically inverse associations between genetically predicted testosterone concentration and dense area (β = − 0.22; 95% CI = − 0.38, − 0.053; p = 0.009) and between genetically predicted estradiol concentration and non-dense area (β = − 3.32; 95% CI = − 5.83, − 0.82; p = 0.009), although results were not consistent across a range of MR approaches. Conclusion: Our findings support a positive causal association between BMI and mammographic non-dense area and an inverse association between BMI and dense area. Evidence was weaker and inconsistent for a causal effect of circulating sex hormone concentrations on mammographic density phenotypes. Based on our findings, associations between circulating sex hormone concentrations and mammographic density phenotypes are weak at best.
CRIS-Team Scopus Importer:2024-05-03
Keywords: BMI; Breast density; Causal inference; Mendelian randomization; Sex hormones

Disseminated tumour cells from the bone marrow of early breast cancer patients: Results from an international pooled analysis - Hartkopf, Andreas D.; Brucker, Sara Y.; Taran, Florin Andrei; Harbeck, Nadia; von Au, Alexandra; Naume, Bjørn; Pierga, Jean Yves; Hoffmann, Oliver; Beckmann, Matthias; Rydén, Lisa; Fehm, Tanja; Aft, Rebecca; et al. (European Journal of Cancer, 2021)
Purpose: Presence of disseminated tumour cells (DTCs) in the bone marrow (BM) has been described as a surrogate of residual disease in patients with early breast cancer (EBC). PADDY (Pooled Analysis of DTC Detection in Early Breast Cancer) is a large international analysis of pooled data that aimed to assess the prognostic impact of DTCs in patients with EBC. Experimental design: Individual patient data were collected from 11 centres. Patients with EBC and available follow-up data in whom BM sampling was performed at the time of primary diagnosis before receiving any anticancer treatment were eligible. DTCs were identified by antibody staining against epithelial cytokeratins. Multivariate Cox regression was used to compare the survival of DTC-positive versus DTC-negative patients. Results: In total, 10,307 patients were included. Of these, 2814 (27.3%) were DTC-positive. DTC detection was associated with higher tumour grade, larger tumour size, nodal positivity, oestrogen receptor and progesterone receptor negativity, and HER2 positivity (all p < 0.001). Multivariate analyses showed that DTC detection was an independent prognostic marker for overall survival, disease-free survival and distant disease-free survival with hazard ratios (HR) and 95% confidence intervals (CI) of 1.23 (95% CI: 1.06–1.43, p = 0.006), 1.30 (95% CI: 1.12–1.52, p < 0.001) and 1.30 (95% CI: 1.08–1.56, p = 0.006), respectively. There was no association between locoregional relapse-free survival and DTC detection (HR 1.21; 95% CI 0.68–2.16; p = 0.512). Conclusions: DTCs in the BM represent an independent prognostic marker in patients with EBC. The heterogeneous metastasis-initiating potential of DTCs is consistent with the concept of cancer dormancy.
CRIS-Team Scopus Importer:2021-07-23
Keywords: Bone marrow; Disseminated tumour cells; Early breast cancer; Micrometastases; Prognosis; Tumour staging

DNA methylation outliers in normal breast tissue identify field defects that are enriched in cancer - Teschendorff, Andrew E.; Gao, Yang; Jones, Allison; Rübner, Matthias; Beckmann, Matthias; Wachter, David; Fasching, Peter; Widschwendter, Martin (Nature Communications, 2016)
Identifying molecular alterations in normal tissue adjacent to cancer is important for understanding cancer aetiology and designing preventive measures. Here we analyse the DNA methylome of 569 breast tissue samples, including 50 from cancer-free women and 84 from matched normal cancer pairs. We use statistical algorithms for dissecting intra- and inter-sample cellular heterogeneity and demonstrate that normal tissue adjacent to breast cancer is characterized by tens to thousands of epigenetic alterations. We show that their genomic distribution is non-random, being strongly enriched for binding sites of transcription factors specifying chromatin architecture. We validate the field defects in an independent cohort and demonstrate that over 30% of the alterations exhibit increased enrichment within matched cancer samples. Breast cancers highly enriched for epigenetic field defects, exhibit adverse clinical outcome. Our data support a model where clonal epigenetic reprogramming towards reduced differentiation in normal tissue is an important step in breast carcinogenesis.
EVALuna2:6810

DNA methylation profiling identifies two distinct subgroups in breast cancers with low hormone receptor expression, mainly associated with HER2 amplification status - Jurmeister, Philipp; Weber, Karsten; Villegas, Sonia; Karn, Thomas; Untch, Michael; Thieme, Anne; Mueller, Volkmar; Taube, Eliane; Fasching, Peter; Schmitt, Wolfgang D.; Marme, Frederik; Stickeler, Elmar; et al. (Clinical Epigenetics, 2021)
Background: Current clinical guidelines suggest that breast cancers with low hormone receptor expression (LowHR) in 1–10% of tumor cells should be regarded as hormone receptor positive. However, clinical data show that these patients have worse outcome compared to patients with hormone receptor expression above 10%. We performed DNA methylation profiling on 23 LowHR breast cancer specimens, including 13 samples with HER2 amplification and compared our results with a reference breast cancer cohort from The Cancer Genome Atlas to clarify the status for this infrequent but important patient subgroup. Results: In unsupervised clustering and dimensionality reduction, breast cancers with low hormone receptor expression that lacked HER2 amplification usually clustered with triple negative breast cancer (TNBC) reference samples (8/10; “LowHR TNBC-like”). In contrast, most specimens with low hormone receptor expression and HER2 amplification grouped with hormone receptor positive cancers (11/13; “LowHR HRpos-like”). We observed highly similar DNA methylation patterns of LowHR TNBC-like samples and true TNBCs. Furthermore, the Ki67 proliferation index of LowHR TNBC-like samples and clinical outcome parameters were more similar to TNBCs and differed from LowHR HRpos-like cases. Conclusions: We here demonstrate that LowHR breast cancer comprises two epigenetically distinct groups. Our data strongly suggest that LowHR TNBC-like samples are molecularly, histologically and clinically closely related to TNBC, while LowHR HRpos-like specimens are closely related to hormone receptor positive tumors.
CRIS-Team Scopus Importer:2021-10-15

DNA mismatch repair gene MSH6 implicated in determining age at natural menopause - Perry, John R. B.; Hsu, Yi-Hsiang; Chasman, Daniel I.; Johnson, Andrew D.; Elks, Cathy; Albrecht, Eva; Andrulis, Irene L.; Beesley, Jonathan; Berenson, Gerald S.; Bergmann, Sven; Bojesen, Stig E.; Bolla, Manjeet K.; et al. (Human Molecular Genetics, 2014)
The length of female reproductive lifespan is associated with multiple adverse outcomes, including breast cancer, cardiovascular disease and infertility. The biological processes that govern the timing of the beginning and end of reproductive life are not well understood. Genetic variants are known to contribute to 50% of the variation in both age at menarche and menopause, but to date the known genes explain <15% of the genetic component. We have used genome-wide association in a bivariate meta-analysis of both traits to identify genes involved in determining reproductive lifespan. We observed significant genetic correlation between the two traits using genome-wide complex trait analysis. However, we found no robust statistical evidence for individual variants with an effect on both traits. A novel association with age at menopause was detected for a variant rs1800932 in the mismatch repair gene MSH6 (P = 1.9 × 10(-9)), which was also associated with altered expression levels of MSH6 mRNA in multiple tissues. This study contributes to the growing evidence that DNA repair processes play a key role in ovarian ageing and could be an important therapeutic target for infertility.
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Documentation Behavior in the CANKADO eHealth-Application and Effects on observed Side Effects - An exploratory Analysis of the PreCycle-Study - Schmidt, M.; Degenhardt, T.; Fasching, Peter; Wurstlein, R.; Lueftner, D.; Kates, R. E.; Schumacher, J.; Wenzel, C.; Schinkoethe, T.; Harbeck, N. (GEBURTSHILFE UND FRAUENHEILKUNDE, 2020)
CRIS-Team WoS Importer:2020-07-31

Documentation in Gynaecologic Oncology: Conflicts between quality management, science, efficacy, and liability Dokumentation in der gynäkologischen Onkologie: Im Spannungsfeld zwischen Qualitätssicherung und Wissenschaft, Ergonomie und Rechtssicherheit - Beckmann, K.; Jud, Sebastian; Hein, Alexander; Heusinger, K.; Bayer, Christian M.; Schwenk, M.; Häberle, Lothar; Beckmann, Matthias (Gynäkologe, 2010)
The rapid growth in medical documentation seen in recent decades has affected gynaecologic oncology as well. Particularly for malignant disorders the need for longitudinal and horizontal documentation, centralisation, guideline conformity, and quality management requires dealing with huge stores of data, often in different systems together (mammography screening, internal patient files, DMP, BQS/AQUA, studies, etc). Thanks in part to these redundancies, the mass of data can take on gigantic proportions. Some relief might be found from increased digitalisation, standardisation, and centralisation urged in the new German National Cancer Plan, mainly with respect to repeat data. © 2010 Springer-Verlag.
CRIS-Team Scopus Importer:2021-07-19
Keywords: Cancer registers; German National Cancer Plan; Quality management; Therapy guidelines

Documentation Time and Effort and Associated Resources for Patients with Primary Breast Cancer from Diagnosis to End of Follow-Up - Results of a Multicentre Validation - Beckmann, Matthias; Sell, C.; Aydogdu, M.; Brucker, S. Y.; Fehm, T.; Janni, W.; Kreienberg, R.; Kuemmel, S.; Neumann, M.; Scharl, A.; Schleicher, B.; Wallwiener, D.; et al. (Gesundheitswesen, 2016)
INTRODUCTION: Tumour documentation is essential for quality assurance of oncological therapies and as a source of reliable information about the in- and outpatient care. The documentation effort and the associated resource consumption were analysed for the example of breast cancer. MATERIAL AND METHODS: The different steps in the care of patients with primary breast cancer in a standardised disease situation were defined from initial diagnosis to the end of the follow-up. After the pilot phase, a multicentre validation (n=7 centres) was performed with the support of the Federal Ministry of Health. The documentation time points were horizontally collected and analysed with regard to amount, duration and personnel expenses. RESULTS: 57% of the documentation costs are caused by the physicians. Regarding the different centres, documentation costs were calculated between € 352.82 and € 1 084.08 per patient from diagnosis to completion of aftercare. Non-certified centres had a reduced documentation effort and thus lower costs. CONCLUSIONS: The results demonstrate the need for a reduction of the documentation effort - particularly for physicians - the most expensive profession in the health system. A quality improvement is expected from the certification with its special requirements. In this context, there is a justified demand for an adequate remuneration of the documentation effort for certified centres. Furthermore, it is necessary to reduce the number of variables for quality assurance and to define them centrally. A comprehensive multi-disciplinary documentation should be achieved. Investments in a single data set and interface enhancements of existing documentation systems should be realised.
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Does Anti-Müllerian hormone vary during a menstrual cycle? A systematic review and meta-analysis - Khodavirdilou, Rasa; Pournaghi, Marjaneh; Rastgar Rezaei, Yeganeh; Hajizadeh, Khadijeh; Khodavirdilou, Lida; Javid, Farzin; Hamdi, Kobra; Shahnazi, Mahnaz; Nouri, Mohammad; Fattahi, Amir; Beckmann, Matthias; Dittrich, Ralf (Journal of Ovarian Research, 2022)
Objective: Numerous studies have indicated that the level of the Anti-Müllerian hormone (AMH), one of the main markers for the ovarian reserve, does not fluctuate throughout a menstrual cycle, while some studies have rejected this finding. The purpose of this systematic and meta-analysis study is to consensus on all contradictory studies that have measured AMH levels throughout the menstrual cycle and to investigate the exact extent of AMH variation in a cycle. Methods: The protocol for this meta-analysis was registered at PROSPERO before data extraction. Relevant studies were identified by systematic search in PubMed, ScienceDirect, Embase, Cochrane Library, and Google Scholar with no limitation on publication date. Longitudinal studies which have evaluated AMH levels in the follicular and luteal phases of an unstimulated (natural) menstrual cycle in healthy women without endocrinology or ovarian disorders were included. We used the JBI Critical Appraisal Checklist for assessing the quality of studies found eligible for meta-analysis. Results: A total of 11 studies involving 733 women with regular menstrual cycles were included. The results showed that the AMH level in the follicular phase was significantly higher than in the luteal phase (95% Cl = 0.11 [0.01 to 0.21]; p < 0.05) and it varies about 11.5% from the luteal phase. The analysis of studies which had also examined the ovulatory phase (n = 380) showed that the serum levels of AMH in the ovulatory phase (about 2.02 ng/ml) did not significantly vary compared to follicular (95% Cl = 0.11 [-0.10 to 0.33]; p = 0.30) and luteal (95% Cl = 0.06 [-0.08 to 0.20]; p = 0.43) phases. Conclusions: According to the results of this study, AMH levels differ between follicular and luteal phases which might be due to ovarian response to the gonadotropins. It seems the phase of AMH measurement needs to be considered for interpretation of the serum AMH test.
CRIS-Team Scopus Importer:2022-07-15
Keywords: Anti mullerian hormone; Fullicular phase; Luteal phase; Menstrual cycle; Meta-analysis; Ovulation; Systematic review

Does anxiety impact the neural processing of child faces in mothers of school-aged children? An ERP study using an emotional Go/NoGo task - Kungl, Melanie; Rutherford, Helena J.V.; Heinisch, Christine; Beckmann, Matthias; Fasching, Peter; Spangler, Gottfried (Social Neuroscience, 2020)
Maternal anxiety during pregnancy and the early postpartum period is associated with heightened neural processing of neutral infant faces as measured by event-related potentials (ERPs). However, less is known about how anxiety shapes neural face processing in mothers of older children. In our study, 36 mothers of 8–10 year old children completed a Go/NoGo task consisting of neutral and emotional (happy, fearful) facial expressions posed by unfamiliar school-aged children while EEG was recorded. Higher levels of maternal anxiety -indexed via self-report- were associated with delayed behavioral responses to children’s fearful faces and increased N170 and LPP amplitudes elicited by children’s neutral faces. While anxiety was also positively related to the LPP elicited by children’s emotional faces, it only led to increased N170 amplitude responses to children’s fearful, but not happy, faces and only when they were NoGo cues. The study replicates and extends prior findings examining the impact of maternal anxiety on neural responses to neutral infant faces to later stages of parenting with further neural markers and emotional expressions being affected. Findings evidence the importance of studying these associations beyond infancy to increase our knowledge about processes potentially underlying the relation between anxiety and less optimal parenting across development.
CRIS-Team Scopus Importer:2020-07-24
Keywords: EEG/ERP; emotional faces; Go/NoGo task; LPP; Maternal anxiety; N170

Does differential HLA-E and -F expression cause an aberrant immune tolerance in preeclampsia and HELLP? - Würfel, Franziska; Hübner, Hanna; Strick, Reiner; Fasching, Peter; Beckmann, Matthias; Wuerfel, Wolfgang; Rübner, Matthias (2016)
EVALuna2:32977

Does Induction of Labor for Preterm Premature Rupture of Membranes at 34 Weeks of Gestation Increase the Risk for Cesarean Section Erhöht die Geburtseinleitung wegen eines frühen vorzeitigen Blasensprungs ab 34+0 SSW das Risiko für einen Kaiserschnitt - Puhl, Alexander; Weiss, Christel; Schneid, Anna; Zahn, Eva; Kraft, Katrina; Pretscher, Jutta; Faschingbauer, Florian; Beckmann, Matthias; Kehl, Sven (Zeitschrift für Geburtshilfe und Neonatologie, 2020)
Purpose Induction of labor at 34 weeks of gestation is often linked to increased risk for cesarean section. Recently, the PPROMT trial demonstrated a higher cesarean section rate when labor wasinduced for preterm premature rupture of membranes (PPROM). The purpose of this study was thereforeto evaluate the success rate of induction of labor for PPROM at 34 and 35 weeks of gestation in comparison with a higher gestational age. Material and Methods In this historic cohort study, cases with labor inductions for PPROM ≥ 34 weeks of gestation were included. Induction of labor at 34 and 35 weeks of gestation (group 1) were compared with those performed at 36 weeks (group 2) and 37 weeks (group 3). Induction of labor was started 12 to 24 hours after (preterm) premature rupture of membranes. Antibiotics were given routinely. The primary outcome was the rate of cesarean section. Results There were significantly more cesarean sections in group 3 in comparison with group 2 (7 vs. 25, p=0.0136). However, univariable and multiple logistic regression analysis of the primary outcome measure showed that there was no impact of the group affiliation on cesarean section rate. Significant parameters influencing the risk of cesarean section were body mass index and Bishop score. Conclusion Induction of labor for PPROM at 34 weeks of gestation is not associated with an increased rate of cesarean section.
CRIS-Team Scopus Importer:2020-11-06
Keywords: induction of labor; moderate preterm birth; premature rupture of membranes; preterm premature rupture of membranes

Does it make sense to refreeze ovarian tissue after unexpected occurrence of endometriosis when transplanting the tissue? - Dietl, Anna; Dittrich, Ralf; Hoffmann, Inge; Denschlag, Dominik; Hanjalic-Beck, Aida; Muller, Andreas; Beckmann, Matthias; Lotz, Laura (Journal of Ovarian Research, 2022)
Background: Ovarian insufficiency is a major concern for long-term cancer survivors. Ovarian tissue cryopreservation for fertility preservation is an emerging technique that has proven successful over the past decade through transplantation of frozen-thawed ovarian tissue. Compared to other established techniques, such as oocyte freezing, ovarian tissue cryopreservation preserves actual organ function and thus the production of sex hormones. Endometriosis in perimenopausal women is rare, however it can be surprising diagnosis in the planned transplantation of cryopreserved ovarian tissue and the already thawed tissue may not be transplanted, so that it has to be refrozen. Results: Ovarian function returned in the patient two months after transplantation, as shown by estrogen production. Ten months after the ovarian tissue transplantation mild stimulation with FSH was initiated in accordance with a low-dose protocol. When ultrasonography revealed a follicle 17 mm in size in the ovarian graft, hCG was added and after follicular puncture one oocyte was obtained. The oocyte could be fertilized by IVF and transferred to the uterus. On day 14 after embryo-transfer, a positive hCG-Level was detected and after an uncomplicated pregnancy a healthy child was delivered. Conclusions: We report the first pregnancy and live birth achieved using transplantation of thawed and refrozen ovarian tissue in a woman treated by chemotherapy and subsequent endometriosis surgery. Refreezing of cryopreserved ovarian tissue is not a hindrance to successful transplantation of ovarian tissue. Against the background of increasing numbers of candidates for transplantation of ovarian tissue is expected that the combination chemotherapy followed by endometriosis will increase.
CRIS-Team Scopus Importer:2022-05-20
Keywords: Cancer; Chemotherapy; Cryopreservation; Endometriosis; Fertility preservation; Iatrogenic ovarian failure; Ovarian tissue transplantation; Refreezing

Does stimulation with human gonadotropins and gonadotropin-releasing hormone agonist enhance and accelerate the developmental capacity of oocytes in human ovarian tissue xenografted into severe combined immunodeficient mice? - Lotz, Laura; Schneider, Heike; Hackl, Janina; Wachter, David; Hoffmann, Inge; Jurgons, Roland; Beckmann, Matthias; Dittrich, Ralf (Fertility and Sterility, 2014)
To assess the capacity of human frozen-thawed ovarian follicles matured in xenografts to form metaphase II (MII) oocytes after xenotransplantation and exogenous stimulation.Prospective controlled animal study.University hospital gynecology research unit.Ovarian fragments were obtained from 17 women with malignant diseases who wished to cryopreserve ovarian tissue for later pregnancy before chemotherapy.Eighty-eight female severe combined immunodeficient (SCID) mice.Cryopreserved human ovarian tissue was grafted into oophorectomized SCID mice. The mice were divided into three groups: Group A received hMG alone every 2 days for a maximum of 24 weeks; group B additionally received nRH agonist (GnRHa) every 4 weeks; and group C was an untreated control group.Follicular density, morphology, proliferation, oocyte maturation, malignant cell contamination.Follicle survival and development were similar in all three groups. No significant interactions between the stimulation protocols and grafting duration were noted. Three MII oocytes were observed in grafted follicles. Two MII oocytes were harvested without stimulation. None of the mice showed signs of reintroduced malignancy, nor did microscopic evaluation of the grafts raise any suspicion of residual malignant disease.After xenotransplantation, human primordial follicles can be matured to MII oocytes even without stimulation. Administering human gonadotropin and GnRHa does not enhance the developmental capacity of xenografted oocytes. The optimal stimulation schedule for grafted tissue remains unknown.
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Does the Presence of Circulating Tumor Cells in High-Risk Early Breast Cancer Patients Predict the Site of First Metastasis-Results from the Adjuvant SUCCESS A Trial - Trapp, Elisabeth K.; Fasching, Peter; Fehm, Tanja; Schneeweiss, Andreas; Mueller, Volkmar; Harbeck, Nadia; Lorenz, Ralf; Schumacher, Claudia; Heinrich, Georg; Schochter, Fabienne; De Gregorio, Amelie; Tzschaschel, Marie; et al. (Cancers, 2022)
Simple Summary Due to recent advances in breast cancer detection and treatment strategies, the number of breast cancer survivors has increased over the past decades. However, breast cancer follow-up guidelines have not changed for years. The presence of CTCs detected during follow-up has been shown to indicate poor prognosis in high-risk breast cancer patients. Here, we evaluated if the presence of CTCs also indicates the site of metastatic disease by analyzing CTC status and metastatic location in 206 patients with distant recurrence from the large adjuvant breast cancer trial SUCCESS A. Patients who were CTC-positive both before and after chemotherapy were more likely to show bone-only first distant disease (37.5% vs. 21.0%) and first distant disease at multiple sites (31.3% vs. 12.6%) than patients without CTCs. These data indicate that CTCs might serve as a liquid biopsy surveillance-marker enabling risk-stratification for deciding on further adjuvant add-on-treatment. The prognostic relevance of circulating tumor cells (CTCs) in breast cancer is well established. However, little is known about the association of CTCs and site of first metastasis. In the SUCCESS A trial, 373 out of 3754 randomized high-risk breast cancer patients developed metastatic disease. CTC status was assessed by the FDA-approved CellSearch(R)-System (Menarini Silicon Biosystems, Bologna, Italy) in 206 of these patients before chemotherapy and additionally in 159 patients after chemotherapy. CTCs were detected in 70 (34.0%) of 206 patients before (median 2 CTCs, 1-827) and in 44 (27.7%) of 159 patients after chemotherapy (median 1 CTC, 1-124); 16 (10.1%) of 159 patients were CTC-positive at both timepoints. The site of first distant disease was bone-only, visceral-only, and other-site-only in 44 (21.4%), 60 (29.1%), and 74 (35.9%) patients, respectively, while 28 (13.6%) patients had multiple sites of first metastatic disease. Patients with CTCs at both timepoints more often showed bone-only first distant disease (37.5% vs. 21.0%) and first distant disease at multiple sites (31.3% vs. 12.6%) than patients without CTCs before and/or after chemotherapy (p = 0.027). In conclusion, the presence of CTCs before and after chemotherapy is associated with multiple-site or bone-only first-distant disease and may trigger intensified follow-up and perhaps further treatment.
CRIS-Team WoS Importer:2022-09-09

Dose adjustment of cisplatin, etoposide, and ifosfamide according to kidney function: a retrospective analysis and implications for medication safety - Grafe, Carolin; Semrau, Sabine; Hein, Alexander; Beckmann, Matthias; Mackensen, Andreas; Dörje, Frank; Fromm, Martin (Naunyn-Schmiedeberg's Archives of Pharmacology, 2018)
Clearance of cisplatin, etoposide, and ifosfamide depends on kidney function and dosages should be adjusted in patients with renal impairment. However, there is still limited data on the adherence of physicians to dosing recommendations for these drugs in cancer patients with renal impairment. Three thousand four hundred forty-eight prescriptions to 369 patients, treated in the Comprehensive Cancer Center of a German university hospital, were retrospectively evaluated. The administered relative doses of cisplatin, etoposide, and ifosfamide were compared with relative doses recommended at the time of prescription according to the patients' creatinine clearance. Cisplatin is contraindicated according to two German summary of product characteristics (SmPC) in patients with a creatinine clearance < 60 mL/min. Nevertheless, 37 cisplatin prescriptions were made for this group of patients (i.e., 2.0% of all cisplatin prescriptions). According to one German SmPC (valid in the year of data analysis), etoposide dosage should be reduced in patients with a creatinine clearance from 15 to 50 mL/min, while it is contraindicated below 15 mL/min. Thirteen etoposide prescriptions were without dose reduction in patients with creatinine clearance from 15 to 50 mL/min (1.5% of all etoposide prescriptions); one patient received etoposide with creatinine clearance below 15 mL/min. In 8.9% of ifosfamide prescriptions, patients did not receive a reduced dose in spite of respective recommendations. Dosages of cisplatin, etoposide, and ifosfamide are not always adjusted as recommended in patients with renal impairment. Consistent international dosing recommendations (e.g., in SmPCs), preferentially included in clinical decision support systems, should be developed to tackle this problem.
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Dose-Response Association of CD8+ Tumor-Infiltrating Lymphocytes and Survival Time in High-Grade Serous Ovarian Cancer - Goode, Ellen L.; Block, Matthew S.; Kalli, Kimberly R.; Vierkant, Robert A.; Chen, Wenqian; Fogarty, Zachary C.; Gentry-Maharaj, Aleksandra; Toloczko, Aleksandra; Hein, Alexander; Bouligny, Aliecia L.; Jensen, Allan; Osorio, Ana; et al. (JAMA Oncology, 2017)
Importance: Cytotoxic CD8+ tumor-infiltrating lymphocytes (TILs) participate in immune control of epithelial ovarian cancer; however, little is known about prognostic patterns of CD8+ TILs by histotype and in relation to other clinical factors. Objective: To define the prognostic role of CD8+ TILs in epithelial ovarian cancer. Design, Setting, and Participants: This was a multicenter observational, prospective survival cohort study of the Ovarian Tumor Tissue Analysis Consortium. More than 5500 patients, including 3196 with high-grade serous ovarian carcinomas (HGSOCs), were followed prospectively for over 24 650 person-years. Exposures: Following immunohistochemical analysis, CD8+ TILs were identified within the epithelial components of tumor islets. Patients were grouped based on the estimated number of CD8+ TILs per high-powered field: negative (none), low (1-2), moderate (3-19), and high (≥20). CD8+ TILs in a subset of patients were also assessed in a quantitative, uncategorized manner, and the functional form of associations with survival was assessed using penalized B-splines. Main Outcomes and Measures: Overall survival time. Results: The final sample included 5577 women; mean age at diagnosis was 58.4 years (median, 58.2 years). Among the 5 major invasive histotypes, HGSOCs showed the most infiltration. CD8+ TILs in HGSOCs were significantly associated with longer overall survival; median survival was 2.8 years for patients with no CD8+ TILs and 3.0 years, 3.8 years, and 5.1 years for patients with low, moderate, or high levels of CD8+ TILs, respectively (P value for trend = 4.2 × 10−16). A survival benefit was also observed among women with endometrioid and mucinous carcinomas, but not for those with the other histotypes. Among HGSOCs, CD8+ TILs were favorable regardless of extent of residual disease following cytoreduction, known standard treatment, and germline BRCA1 pathogenic mutation, but were not prognostic for BRCA2 mutation carriers. Evaluation of uncategorized CD8+ TIL counts showed a near-log-linear functional form. Conclusions and Relevance: This study demonstrates the histotype-specific nature of immune infiltration and provides definitive evidence for a dose-response relationship between CD8+ TILs and HGSOC survival. That the extent of infiltration is prognostic, not merely its presence or absence, suggests that understanding factors that drive infiltration will be the key to unraveling outcome heterogeneity in this cancer.
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Double-balloon catheter and sequential oral misoprostol versus oral misoprostol alone for induction of labour at term: a retrospective cohort study - Kehl, Sven; Weiss, Christel; Dammer, Ulf; Heimrich, Jutta; Beckmann, Matthias; Faschingbauer, Florian; Suetterlin, Marc (European Journal of Obstetrics Gynecology and Reproductive Biology, 2016)
OBJECTIVE: To evaluate the efficacy of induction of labour using a double-balloon catheter and, if necessary, sequential oral misoprostol without delay after removal of the catheter, in comparison with oral misoprostol alone. STUDY DESIGN: This retrospective cohort study included women undergoing induction of labour with oral misoprostol or double-balloon catheter with sequential oral misoprostol in singleton pregnancies at term. The catheter was placed in the evening and removed when there was no onset of labour within 12h. Then oral misoprostol was started within 3h. Primary outcome measure was the caesarean section rate. RESULTS: There were 13,082 deliveries during the study period with 3466 labour inductions out of which 1032 were eligible and analysed. The caesarean section rate was significantly lower in the double-balloon catheter group (26.1% vs. 17.3, p=0.021). Furthermore, in the combination group, the induction-to-delivery interval was shorter (median values 1144 vs. 1365min, p=0.001) and there were more deliveries within 24h (51.9 vs. 64.7%, p=0.003) and 48h (87.4 vs. 95.8%, p=0.002). When stratifying for parity, there were less caesarean sections in the combination group (37.2% vs. 24.2%, p=0.015) in nulliparous women, too. In both, nulliparous and parous women, the induction-to-delivery interval was shorter (1742 vs. 1400min, 0.005; 1020 vs. 912min, p=0.018). Especially in parous women, the rates of delivery within 24h (62.6% vs. 79.0%, p=0.007) and 48h (88.6% vs. 99.0%, p=0.007) were higher in the combination group. CONCLUSION: Double-balloon catheter and sequential oral misoprostol without long delay in absent onset of labour after removal of the catheter resulted in less caesarean section and shorter induction-to-delivery interval in comparison with oral misoprostol alone.
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Double-balloon catheter and sequential vaginal prostaglandin E2 versus vaginal prostaglandin E2 alone for induction of labor after previous cesarean section - Kehl, Sven; Weiss, Christel; Wamsler, Michael; Beyer, Jana; Dammer, Ulf; Heimrich, Jutta; Faschingbauer, Florian; Suetterlin, Marc; Beckmann, Matthias; Schleussner, Ekkehard (Archives of Gynecology and Obstetrics, 2016)
PURPOSE: To evaluate the efficacy of inducing labor using a double-balloon catheter and vaginal prostaglandin E2 (PGE2) sequentially, in comparison with vaginal PGE2 alone after previous cesarean section. METHODS: A total of 264 pregnant women with previous cesarean section undergoing labor induction at term were included in this prospective multicentre cohort study. Induction of labor was performed either by vaginal PGE2 gel or double-balloon catheter followed by vaginal PGE2. The primary outcome measure was the cesarean section rate. RESULTS: The cesarean section rate was 37 % without any statistically significant difference between the two groups (PGE2: n = 41, 37 % vs. balloon catheter/PGE2: n = 41, 42 %; P = 0.438). The median (range) number of applications of PGE2 [2 (1-10) versus 1 (0-8), P < 0.001] and the total amount of PGE2 used in median (range) mg [2 (1-15) vs. 1 (0-14), P = 0.001] was less in the balloon catheter/PGE2 group. Factors significantly increasing risk for cesarean section were "no previous vaginal delivery" (OR 5.391; CI 2.671-10.882) and "no oxytocin augmentation during childbirth" (OR 2.119; CI 1.215-3.695). CONCLUSIONS: The sequential application of double-balloon catheter and vaginal PGE2 is as effective as the sole use of vaginal PGE2 with less applications and total amount of PGE2.
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Economic and Humanistic Burden of Triple-Negative Breast Cancer: A Systematic Literature Review - Huang, Min; Haiderali, Amin; Fox, Grace E.; Frederickson, Andrew; Cortes, Javier; Fasching, Peter; O'Shaughnessy, Joyce (Pharmacoeconomics, 2022)
Background Triple-negative breast cancer (TNBC) accounts for 10-20% of all breast cancers (BCs). It is more commonly diagnosed in younger women and often has a less favorable prognosis compared with other BC subtypes. Objective The objective of this study was to provide a literature-based extensive overview of the economic and humanistic burden of TNBC to assist medical decisions for healthcare payers, providers, and patients. Methods A systematic literature review was performed using multiple databases, including EMBASE, MEDLINE, Econlit, the Cochrane Central Register of Controlled Trials, and the Cochrane Database of Systematic Reviews, from database inception to 16 May 2021. In addition, a targeted search was performed in the Northern Light Life Sciences Conference Abstracts database from 2016 through June 2021. The bibliographies of included articles were reviewed to identify other potentially relevant publications. Quality assessment of the included studies was conducted. Results The review identified 19 studies assessing the economic burden and 10 studies assessing the humanistic burden of TNBC. Studies varied widely in study design, settings, patient populations, and time horizons. The estimates of mean per-patient annual direct medical costs ranged from around 20,000 to over 100,000 in stage I-III TNBC and from 100,000 to 300,000 in stage IV TNBC. Healthcare costs and resource utilization increased significantly with disease recurrence, progression, and increased cancer stage or line of therapy. Compared with the costs of systemic anticancer therapy, cancer management costs comprised a larger portion of total direct costs. The estimates of indirect costs due to productivity loss ranged from 207 to 1573 per patient per month (all costs presented above were adjusted to 2021 US dollars). Cancer recurrence led to significantly reduced productivity and greater rates of leaving the workforce. A rapid deterioration of health utility associated with disease progression was observed in TNBC patients. Treatment with pembrolizumab or talazoparib showed significantly greater improvements in health-related quality of life (HRQoL) compared with chemotherapy, as measured by EORTC QLQ-C30, QLQ-BR23, and FACT-B. Conclusion TNBC is associated with a substantial economic burden on healthcare systems and societies and considerably reduced productivity and HRQoL for patients. This study synthesized the published literature on the economic and humanistic burden of TNBC and highlighted the need for continued research due to the rapidly changing landscape of TNBC care.
CRIS-Team WoS Importer:2022-02-11

Editorial: The potential for precision medicine to improve care and speed the development of new treatments in breast and gynecologic malignancies - Konecny, Gottfried E.; Fasching, Peter (Current Opinion in Obstetrics & Gynecology, 2019)
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Editor's Comment on the Review of the German IVF Register and the Subsequent Discussion - Beckmann, Matthias (Geburtshilfe und Frauenheilkunde, 2016)
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Effect of a comprehensive lifestyle intervention program on body weight and health behavior in women with breast cancer: Results from a randomized controlled trial - Hauner, Dagmar; Günther, Julia; Schederecker, Florian; Donik, Lara; Meyer, Dorothy; Hermsdörfer, Joachim; Friedl, Thomas W.P.; Rack, Brigitte; Beckmann, Matthias; Janni, Wolfgang; Hauner, Hans (Clinical Nutrition, 2024)
Background: Both overweight/obesity and a Western lifestyle are associated with a poorer prognosis in women with breast cancer. The primary aim of this analysis was to examine the effect of a telephone-delivered lifestyle intervention program on reducing body weight and waist circumference, decreasing cardiovascular risk factors and improving lifestyle. Design: Data is derived from an open-label, randomized, controlled phase III study that evaluated two chemotherapy regimens and the impact of a 2-year lifestyle intervention on disease-free survival and secondary outcomes in women with intermediate-risk to high-risk breast cancer. Initially, 2292 women with a body mass index (BMI) between 24 and 40 kg/m2 were randomized into one of two arms of the lifestyle intervention study. After accounting for dropout, 1785 participants remained: 776 in the intervention group (IG) who received a telephone-delivered lifestyle intervention supported by mailed materials, and 1009 in the low-level intervention group (LLIG) who received only mailed educational materials with general recommendations for a healthy lifestyle. Body weight, waist circumference, dietary intake, physical activity, and cardiovascular disease risk parameters were measured repeatedly throughout the intervention and a subsequent 2-year follow-up period. Linear mixed models for repeated measures were used to assess differences in study outcomes between the LLIG and IG at each measured time point. Results: IG participants showed a mean weight loss of −2.7 kg (kg) (versus +0.4 kg, LLIG) at 6 months, −2.8 kg (vs. +0.8 kg, LLIG) at 12 months and −1.8 kg at 24 months (versus +0.9 kg, LLIG). Significant between-group differences for weight loss and reduced waist circumference were observed at all time points until the end of the lifestyle intervention (all p-values < 0.0001), including post-intervention. Reduced energy intake and a higher alternate healthy eating index (AHEI) score in the IG was detected during the lifestyle intervention (AHEI at 24 months: IG 49.1% versus LLIG 42.0%, p < 0.001). Modest significant improvements in several cardiovascular risk factors were observed during the intervention, including fasting plasma glucose, HbA1c, systolic and diastolic blood pressure, and lipids. Conclusions: A mainly telephone-delivered lifestyle intervention program can reduce body weight and waist circumference, improve diet quality, and decrease cardiometabolic risk in women with overweight/obesity and newly diagnosed, human epidermal growth factor receptor 2 (HER2)/neu-negative, intermediate-risk to high-risk breast cancer. Weight loss, reduced waist circumference and improved dietary patterns were maintained for up to two years post-intervention. Trial registration: The protocol was registered under the EU Clinical Trials Register, https://www.clinicaltrialsregister.eu/, identifier: 2008-005453-38.
CRIS-Team Scopus Importer:2024-07-26
Keywords: Breast cancer; Diet quality; Lifestyle intervention; Obesity; Overweight; Weight loss

Effect of Denosumab Added to 2 Different nab-Paclitaxel Regimens as Neoadjuvant Therapy in Patients with Primary Breast Cancer: The GeparX 2 × 2 Randomized Clinical Trial - Blohmer, Jens-Uwe; Link, Theresa; Reinisch, Mattea; Just, Marianne; Untch, Michael; Stotzer, Oliver; Fasching, Peter; Schneeweiss, Andreas; Wimberger, Pauline; Seiler, Sabine; Huober, Jens; Thill, Marc; et al. (JAMA Oncology, 2022)
Importance: Adjuvant denosumab might improve disease-free survival in hormone receptor (HR)-positive primary breast cancer (BC). The optimal neoadjuvant nab-paclitaxel schedule in terms of efficacy and safety is unclear. Objective: To determine whether adding denosumab to anthracycline/taxane-containing neoadjuvant chemotherapy (NACT) increases the pathological complete response (pCR) rate and which nab-paclitaxel schedule is more effective in the NACT setting. Design, Setting, and Participants: The GeparX was a multicenter, prospective, open-label, phase 2b, 2 × 2 randomized clinical trial conducted by GBG and AGO-B at 38 German sites between February 2017 and March 2019. The analysis data set was locked September 4, 2020; analysis was completed November 13, 2020. Patients had unilateral or bilateral primary BC, stage cT2-cT4a-d or cT1c, with either clinically node-positive or pathologically node-positive or HR-negative disease, or Ki-67 proliferation index greater than 20%, or ERBB2 (formerly HER2)-positive BC. Interventions: Patients were randomized to receive or not receive denosumab, 120 mg subcutaneously every 4 weeks for 6 cycles, and either nab-paclitaxel, 125 mg/m2weekly for 12 weeks or days 1 and 8 every 3 weeks for 4 cycles (8 doses), followed by 4 cycles of epirubicin/cyclophosphamide, 90/600 mg/m2(every 2 weeks or every 3 weeks). Carboplatin was given in triple-negative BC (TNBC), and trastuzumab biosimilar ABP980 plus pertuzumab was given in ERBB2-positive BC (ERBB2-positive substudy). Main Outcomes and Measures: The primary outcome was pCR rates between arms for each randomization. Results: A total of 780 female (n = 779) and male (n = 1) patients (median [range] age, 49.0 [22-80] years) were randomized to the 4 treatment groups. The pCR (ypT0 ypN0) rate was 41.0% (90% CI, 37%-45%) with denosumab vs 42.8% (90% CI, 39%-47%) (P =.58) without denosumab, irrespective of BC subtype. Nab-paclitaxel weekly resulted in a significantly (significance level of α =.10) higher pCR rate of 44.9% (90% CI, 41%-49%) vs 39.0% (90% CI, 35%-43%) (P =.06) with nab-paclitaxel days 1 and 8 every 3 weeks. The pCR rates for nab-paclitaxel schedules in subgroups were only significantly different for TNBC (60.4% vs 50.0%; P =.06). Grade 3 to 4 toxic effects did not differ with or without denosumab. Nonhematologic toxic effects of grade 3 to 4 were higher with nab-paclitaxel weekly (33.7% vs 24.1%; P =.004). Conclusions and Relevance: In this randomized clinical trial, denosumab added to anthracycline/taxane-based NACT did not improve pCR rates. Nab-paclitaxel at a dosage of 125 mg/m2weekly significantly increased the pCR rate compared with the days 1 and 8, every-3-weeks schedule overall and in TNBC, but generated higher toxicity. Trial Registration: ClinicalTrials.gov Identifier: NCT02682693.
CRIS-Team Scopus Importer:2022-06-03

Effect of Premature Rupture of Membranes on Induction of Labor: A Historical Cohort Study - Kehl, Sven; Weiss, Christel; Dammer, Ulf; Baier, Friederike; Faschingbauer, Florian; Beckmann, Matthias; Suetterlin, Marc; Pretscher, Jutta (Geburtshilfe und Frauenheilkunde, 2017)
Objective: The aim of this study was to assess the influence of premature rupture of membranes (PROM) on the induction of labor. Material and Method: This historical cohort study analyzed 1861 inductions of labor at term using misoprostol which occurred between 2010 and 2015. Exclusion criteria included intrauterine fetal death, previous cesarean section, and fetal structural or chromosomal anomalies. Induction of labor for PROM (PROM group) was compared to induction for other indications (no-PROM group); the primary outcome measure was the cesarean section rate. Results: The cesarean section rate for the PROM group was significantly lower (21.9% vs. 26.3%, p = 0.029). The induction-to-delivery interval was shorter (mean: 972 [854 - 6734] min vs. 1741 [97 - 10 834] min, p < 0.0001) and the rates of vaginal birth within 24 hours (80.9 vs. 52.0%, p = 0.0001) and 48 hours (98.4 vs. 85.3%, p = 0.0001) were higher in the PROM group. The impact of PROM on the cesarean section rate was not significant in multivariate analysis; however, PROM was found to have the greatest effect on the induction-to-delivery interval (p < 0.0001). Conclusion: Premature rupture of membranes significantly affects various outcome measures when delivery is induced, particularly the induction-to-delivery interval.
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Effects of an App-Based Mindfulness Intervention during Pregnancy on the Infant’s Prenatal Androgen Exposure: A Randomized Controlled Pilot Trial - Siegmann, Eva-Maria; Eichler, Anna; Buchholz, Verena Nadine; Gerlach, Jennifer; Pontones, Constanza; Titzmann, Adriana; Arnaud, Nicolas; Consortium, Imac Mind; Mühle, Christiane; Beckmann, Matthias; Fasching, Peter; Kratz, Oliver; et al. (Journal of Clinical Medicine, 2023)
Prenatal androgen exposure modulates the development of the brain, with lasting effects on its function and behavior over the infant’s life span. Environmental factors during pregnancy, in particular maternal stress, have been shown to influence the androgen load of the unborn child. We here addressed the research gap on whether a mindfulness intervention or a pregnancy education administered to pregnant women more affects the androgen exposure of the unborn child (quantified by the proxies of second-to-fourth digit length ratio (2D:4D) and anogenital distance assessed one year after delivery and at delivery, respectively). Moreover, we tested the mindfulness intervention’s effects on maternal perceived stress, anxiety, depressiveness, and mindfulness. Pregnant women (gestation weeks 8–14) were randomized to a 15-week app-based mindfulness-oriented intervention (N = 72) or a pregnancy education intervention (control condition; N = 74). The mindfulness-oriented group did not significantly differ from the pregnancy education group in infants’ 2D:4D or anogenital distance (partial η2 ≤ 0.01) or in maternal stress, anxiety, depressiveness, or mindfulness. However, the descriptive results indicate that across pregnancy, stress and anxiety decreased and mindfulness increased in both groups. Overall, this study did not show that the mindfulness intervention (relative to the pregnancy education) reduced the prenatal androgen exposure of the unborn children or improved the maternal outcomes significantly.
CRIS-Team Scopus Importer:2023-10-20
Keywords: digit ratio; mindfulness; prenatal programming

Effects of bacteria on male fertility: Spermatogenesis and sperm function - Oghbaei, Hajar; Rastgar Rezaei, Yeganeh; Nikanfar, Saba; Zarezadeh, Reza; Sadegi, Mohammadreza; Latifi, Zeinab; Nouri, Mohammad; Fattahi, Amir; Ahmadi, Yadollah; Bleisinger, Nathalie (Life Sciences, 2020)
Bacterial infection can negatively affect different parts of the male genital tract and subsequently cause impaired spermatogenesis and male fertility. However, most of the previous studies have focused on the infected organs of the male genital tract and there are not many studies that investigated the direct effect of bacteria on sperm and their mechanism of action. Interestingly, bacteria can induce different damages on sperm cells such as DNA fragmentation, cell membrane peroxidation, and acrosome impairment. Such negative effects can be mediated by bacteria-secreted toxins and metabolites or by direct attachment of bacteria on the sperm cells and subsequent activation of signaling pathways related to oxidative stress, apoptosis, and inflammation. These bacteria-induced changes can impair semen parameters and subsequently cause infertility. Given the significant destructive effect of some bacteria on sperm function and male fertility, in this study, we reviewed the impact of male urogenital bacteria on spermatogenesis and sperm functions as well as the underlying mechanisms by which the bacteria can damage sperm.
CRIS-Team Scopus Importer:2020-06-26
Keywords: Apoptosis; Bacteria; DNA fragmentation; Fertility; Sperm

Effects of interactions between progesterone and prostaglandin on uterine contractility in a perfused swine uterus model - Kuenzel, Julian; Geisler, Klaudija; Maltaris, Theodoros; Mueller, Andreas; Hoffmann, Inge; Schneider, Heike; Beckmann, Matthias; Dittrich, Ralf; Oppelt, Patricia (In Vivo, 2014)
Uterine quiescence at the time of embryo transfer is a prerequisite for successful in vitro fertilization (IVF). This study assessed whether prostaglandin-induced contractions in the perfused swine uterus can be reduced by progesterone.Fifty-eight non-pregnant swine uteri were perfused using an established extracorporeal perfusion model. Intrauterine pressure changes during perfusion with prostaglandin (PG) administration (PGE1, PGE2, PGF2?) and progesterone (1 pg/ml, 10 pg/ml, 25 pg/ml, 50 pg/ml) were assessed using an intrauterine double-chip microcatheter.The contraction-stimulating effect of PGs was clearly reduced by progesterone. Only PGE1 still triggered relevant contractions during continuous perfusion with progesterone solution, up to a concentration of 10 pg/ml. With PGE2 and PGF2?, a clear reduction of uterine contractility was observed even at at a progesterone concentration of 1 pg/ml.The extracorporal perfusion model of swine uteri shows that PG-induced contractions can be reduced in a dose-dependent manner by progesterone.
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Effects of prenatal alcohol consumption on cognitive development and ADHD-related behaviour in primary-school age: a multilevel study based on meconium ethyl glucuronide - Eichler, Anna; Hudler, Linda; Grunitz, Juliane; Grimm, Jennifer; Raabe, Eva; Goecke, Tamme W.; Fasching, Peter; Beckmann, Matthias; Kratz, Oliver; Moll, Gunther; Kornhuber, Johannes; Heinrich, Hartmut (The journal of child psychology and psychiatry, 2018)
BACKGROUND: Alcohol intake during pregnancy is considered to be a risk factor for child development. Child biomarkers of intrauterine alcohol exposure have been rarely studied. We investigated whether a meconium alcohol metabolite (ethyl glucuronide, EtG) was associated with cognitive development, ADHD-related behaviour and neurophysiological markers of attention and executive control of children at primary-school age. METHODS: Mothers provided self-report on prenatal alcohol consumption during their 3rd trimester. Meconium samples were collected at birth. A total of 44 children with a meconium EtG above the detection limit (≥10 ng/g) and 44 nonexposed matched controls were compared. A second threshold (≥154 ng/g) was applied to study the dose effects. When children reached primary-school age, mothers rated ADHD-related behaviour, child cognitive development was measured using an IQ test battery, and event-related potentials were recorded during a cued go/nogo task. RESULTS: Children in both EtG-positive groups allocated fewer attentional resources than controls to the go/nogo task (reduced P3 component in go-trials). Children with a meconium EtG above 154 ng/g were also found to have an IQ that was six points lower than the other groups. Within the EtG ≥ 154 ng/g group, there was a positive correlation between EtG value and ADHD-related behaviour. These significant effects were not observed in relation to the maternal self-report data. CONCLUSIONS: Associations between EtG and cognitive deficits, attentional resource capacity and ADHD-related behaviour could be documented with effects that were partially dose-dependent. In addition to maternal self-reports, this biomarker of intrauterine alcohol exposure may be considered as a predictor of child development.
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Effects of whole-body electromyostimulation combined with individualized nutritional support on body composition in patients with advanced cancer: a controlled pilot trial - Schink, Kristin; Herrmann, Hans J.; Schwappacher, Raphaela; Meyer, Julia; Orlemann, Till; Waldmann, Elisabeth; Wullich, Bernd; Kahlmeyer, Andreas; Fietkau, Rainer; Lubgan, Dorota; Beckmann, Matthias; Hack, Carolin; et al. (BMC Cancer, 2018)
BACKGROUND: Physical exercise and nutritional treatment are promising measures to prevent muscle wasting that is frequently observed in advanced-stage cancer patients. However, conventional exercise is not always suitable for these patients due to physical weakness and therapeutic side effects. In this pilot study, we examined the effect of a combined approach of the novel training method whole-body electromyostimulation (WB-EMS) and individualized nutritional support on body composition with primary focus on skeletal muscle mass in advanced cancer patients under oncological treatment. METHODS: In a non-randomized controlled trial design patients (56.5% male; 59.9 ± 12.7 years) with advanced solid tumors (UICC III/IV, N = 131) undergoing anti-cancer therapy were allocated to a usual care control group (n = 35) receiving individualized nutritional support or to an intervention group (n = 96) that additionally performed a supervised physical exercise program in form of 20 min WB-EMS sessions (bipolar, 85 Hz) 2×/week for 12 weeks. The primary outcome of skeletal muscle mass and secondary outcomes of body composition, body weight and hand grip strength were measured at baseline, in weeks 4, 8 and 12 by bioelectrical impedance analysis and hand dynamometer. Effects of WB-EMS were estimated by linear mixed models. Secondary outcomes of physical function, hematological and blood chemistry parameters, quality of life and fatigue were assessed at baseline and week 12. Changes were analyzed by t-tests, Wilcoxon signed-rank or Mann-Whitney-U-tests. RESULTS: Twenty-four patients of the control and 58 of the WB-EMS group completed the 12-week trial. Patients of the WB-EMS group had a significantly higher skeletal muscle mass (0.53 kg [0.08, 0.98]; p = 0.022) and body weight (1.02 kg [0.05, 1.98]; p = 0.039) compared to controls at the end of intervention. WB-EMS also significantly improved physical function and performance status (p < 0.05). No significant differences of changes in quality of life, fatigue and blood parameters were detected between the study groups after 12 weeks. CONCLUSIONS: Supervised WB-EMS training is a safe strength training method and combined with nutritional support it shows promising effects against muscle wasting and on physical function in advanced-stage cancer patients undergoing treatment. TRIAL REGISTRATION: ClinicalTrials.gov NCT02293239 (Date: November 18, 2014).
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Effekte von Peer Teaching in einem geburtshilflich-gynäkologischen Praktikum - Frobenius, Wolfgang; Ganslandt, Thomas; Juenger, J.; Beckmann, Matthias; Cupisti, S. (Geburtshilfe und Frauenheilkunde, 2009)
Obstetrics gynecology medical education peer teaching block course OSCE Background: Due to limited staffing resources and the need to preserve patients' privacy, it is difficult to improve the assessed practical courses in gynecology required by law for the licensing of physicians in Germany (Ärztliche Approbations- ordnung, ÄAppO). A previously published project showed that including structured practical teaching (skills training) using suitable obstetric and gynecological models in courses taught by specially trained student teachers (peer teachers) represents a potential solution to the problem. However, there are as yet no data regarding the effectiveness of this approach. Aim: Aim of the study was to determine the effectiveness of a peer-assisted skills training for students as part of a gynecological and obstetric practical course for theoretical and practical examinations (objective structured clinical examination, mini-OSCE) (primary end point). How do students who have been taught in this way rate the educational quality, teaching atmosphere, personal learning progress, and this type of practical course overall (secondary end points)? Methods: Following the implementation of a skills training section during a practical course, students (n = 139) were randomly assigned to 24 groups. Most groups consisted of six participants. Half of these groups, with a total of 71 students, received peer teaching during skills training, while the other half (n = 68) were taught by postgraduate lecturers. The rest of the one-week practical course, including the theoretical and practical examinations, was identical for all groups. The results of a theoretical and practical examination, also newly implemented (primary end point) and the results of the evaluation before (comparability of the groups) and after the practical course (secondary end points) were analyzed. Results: The groups taught by postgraduate lecturers did not differ with regard to age, sex, num die Ergebnisse der Evaluation vor (Vergleichbarkeit der Gruppen) und nach dem Praktikum (sekundare Endpunkte). Ergebnisse: Die von postgraduierten Dozenten unterrichteten Gruppen unterschieden sich hinsichtlich Alter, Geschlecht, Semesterzahl und fachspezifischer Vorbildung nicht von den durch Peer Teacher geschulten Studierenden. An den 3 überwiegend praktischen OSKE-Stationen erzielten die Studierenden der Post- graduierten-Gruppe 58,26±3,2 (95%-KI 57,5-59,5) von 62 Punkten, in der Peer-Teacher-Gruppe waren es 58,82±2,6 (95%-KI 58,2-59,4) (p = 0,27). Bei der Bearbeitung der Stationen mit Fall- darstellungen, fur die beiden Gruppen in Seminaren von postgra- duierten Dozenten vermittelter Stoff relevant war, erreichte die Postgraduierten-Gruppe 26,52±3,2 (95%-KI 25,7-27,3) von 30 Punkten, in der Peer-Teacher-Gruppe waren es 26,29 ±2,7 (95%-KI 25,6-27,0) (p = 0,64). Auch in der abschließenden Evaluation hinsichtlich Motivation der Ausbilder, Lernklima sowie Effektivität der praktischen Prüfungsvorbereitung gab es keine signifikanten Unterschiede. Die postgraduierten Dozenten schnitten lediglich bei der Vermittlung des theoretischen Hintergrunds und der Beantwortung von Fragen signifikant besser ab als die Peer Teacher. Schlussfolgerung: Zur Vermittlung der Prinzipien grundlegender praktischer ärztlicher Fertigkeiten in einem frauenheilkund- lichen Blockpraktikum ist ein Teaching durch speziell geschulte Peers ebenso effektiv wie der Unterricht durch postgraduierte Dozenten. ber of completed semesters, or prior specialist training from the students who were taught by the peer teachers. In the purely practical OSCE stations, the students in the postgraduate group achieved 58.26 ±3.2 (95 % CI, 57.5-59.5) out of a total of 62 points, while in the peer teacher group they scored 58.82 ±2.6 (95% CI, 58.2-59.4) (p = 0.27). In dealing with the case descriptions, for which material taught to both groups in seminars by postgraduate lecturers was relevant, the postgraduate group achieved 26.52±3.2 (95% CI, 25.7-27.3) of 30 points, while in the peer teacher group the figure was 26.29 ±2.7 (95% CI, 25.6-27.0) (p = 0.64). In the final evaluation regarding the motivation of the trainers, the teaching atmosphere, and the effectiveness of preparation for the practical examination, no significant differences were found. The postgraduate lecturers only had significantly better results than the peer teachers when conveying the theoretical background and responding to questions. Conclusions: To communicate the principles of basic practical medical skills in a gynecological practical course, teaching by specially trained peers is just as effective as teaching by postgraduate teachers. © Georg Thieme Verlag KG Stuttgart.
CRIS-Team Scopus Importer:2021-11-16

Efficacy and safety of AEZS-108 (LHRH agonist linked to doxorubicin) in women with advanced or recurrent endometrial cancer expressing LHRH receptors: a multicenter phase 2 trial (AGO-GYN5) - Emons, Guenter; Gorchev, Grigor; Harter, Philipp; Wimberger, Pauline; Staehle, Anne; Hanker, Lars; Hilpert, Felix; Beckmann, Matthias; Dall, Peter; Gruendker, Carsten; Sindermann, Herbert; Sehouli, Jalid (International Journal of Gynecological Cancer, 2014)
Advanced or recurrent endometrial cancer (EC) no longer amenable to surgery or radiotherapy is a life-threatening disease with limited therapeutic options left. Eighty percent of ECs express receptors for luteinizing hormone-releasing hormone (LHRH), which can be targeted by AEZS-108 (zoptarelin doxorubicin acetate). This phase 2 trial was performed to assess the efficacy and safety of AEZS-108 in this group of patients.Patients had FIGO (Fédération Internationale de Gynécologie et d'Obstétrique) III or IV or recurrent EC, LHRH receptor-positive tumor status, and at least had 1 measurable lesion (Response Evaluation Criteria in Solid Tumors). Prior anthracycline therapy was not allowed. Patients received AEZS-108 as a 2-hour infusion on day 1 of a 21-day cycle. The treatment was continued for a maximum of 6 to 8 cycles. The primary end point was the response rate determined by the Response Evaluation Criteria in Solid Tumors.From April 2008 to November 2009, 44 patients were included in the study at 8 centers in Germany (AGO) and 3 centers in Bulgaria. Forty-three of these patients were eligible. Two (5%) patients had a complete remission, and 8 (18%) achieved a partial remission. Stable disease for at least 6 weeks was observed in 44%. The median time to progression was 7 months, and the median overall survival was 15 months. The most frequently reported grade 3 or 4 adverse effects were neutropenia (12%) and leucopenia (9%).AEZS-108, an LHRH-agonist coupled to doxorubicin, has significant activity and low toxicity in women with advanced or recurrent LHRH receptor-positive EC, supporting the principle of receptor-mediated targeted chemotherapy.
EVALuna2:17445

Efficacy and safety of everolimus plus exemestane in patients with hormone receptor-positive, HER-2-negative advanced breast cancer: Results from the open-label, multicentre, non-interventional BRAWO study - Lüftner, Diana; Schuetz, Florian; Schneeweiss, Andreas; Hartkopf, Andreas; Bloch, Wilhelm; Decker, Thomas; Uleer, Christoph; Stötzer, Oliver; Foerster, Frank; Schmidt, Marcus; Mundhenke, Christoph; Tesch, Hans; et al. (International Journal of Cancer, 2024)
BRAWO, a real-world study, assessed the efficacy, quality of life (QoL) and safety of EVE + EXE in postmenopausal women with HR+/HER2– advanced breast cancer (ABC) in routine clinical practice. Postmenopausal women with HR+/HER2-ABC with recurrence or progression after a NSAI were included. Primary Observation parameters included the evaluation of the effectiveness of EVE + EXE. A multivariate-analysis using Cox proportional hazard model was built to identify predictors of progression. Overall, 2100 patients were enrolled (August 2012–December 2017); 2074 were evaluable for efficacy and safety analyses. Majority of patients (60.6%) received EVE + EXE as first (28.7%) or second-line (31.9%) therapy. Visceral metastases were present in 54.1% patients. Median progression-free survival (mPFS) reported as 6.6 months (95%CI: 6.3–7.0). Multivariate-analysis in a subset of patients (n = 1837) found higher body mass index (BMI) and non-visceral metastases to be independent predictors of favorable PFS. Patients with a BMI of 20 to <25 had a mPFS of 6.0 (95%CI: 5.4–6.4) and those with a BMI ≥30 had mPFS of 8.5 (95%CI: 6.9–9.9). 41.2% patients achieved stable disease and 7.3% partial response. No major changes were observed QoL; 86.4% patients received stomatitis prophylaxis and 41.4% experienced EVE related AEs of stomatitis, mainly low grade. AEs occurred in 91.2% of patients, of which stomatitis (42.6%) and fatigue (19.8%) were most frequent. The BRAWO study provides real-world evidence of efficacy and safety of EVE + EXE in patients with HR+, HER2− ABC. A high BMI and the absence of visceral metastases were independent predictors of PFS in this cohort of patients.
CRIS-Team Scopus Importer:2024-05-10
Keywords: advanced breast cancer; everolimus; exemestane; HER2–; HR+

Efficacy and safety of everolimus plus exemestane in postmenopausal women with hormone receptor-positive, human epidermal growth factor receptor 2-negative locally advanced or metastatic breast cancer: Results of the single-arm, phase IIIB 4EVER trial - Tesch, Hans; Stoetzer, Oliver; Decker, Thomas; Kurbacher, Christian M.; Marme, Frederik; Schneeweiss, Andreas; Mundhenke, Christoph; Distelrath, Andrea; Fasching, Peter; Lux, Michael P.; Lueftner, Diana; Hadji, Peyman; et al. (International Journal of Cancer, 2019)
In BOLERO-2, adding everolimus to exemestane resulted in a twofold increase in median progression-free survival (PFS) vs exemestane in postmenopausal women with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2−) advanced breast cancer (aBC) after progression on a non-steroidal aromatase inhibitor (NSAI). Here, we report on the open-label, single-arm, phase IIIB 4EVER trial (NCT01626222). This trial evaluated the clinical effectiveness of everolimus plus exemestane in postmenopausal women with HR+, HER2− aBC who had progressed on or after an NSAI, but with no restrictions on the time of progression after NSAI, prior chemotherapy for advanced disease or previous exemestane. The primary endpoint was overall response rate (ORR; i.e. the percentage of patients with a best overall response of complete or partial response per RECIST 1.1) within the first 24 weeks of treatment. Secondary endpoints included PFS, overall survival, safety and health-related quality of life. Between June 2012 and November 2013, 299 patients were enrolled at 82 German centers: 281 patients were evaluable for efficacy and 299 for safety. The ORR was 8.9% (95% confidence interval [CI]: 5.8–12.9%). Median PFS was 5.6 months (95% CI: 5.4–6.0 months). The most frequent grade 3/4 adverse events were stomatitis (8.4%), general physical health deterioration (6.7%), dyspnea (4.7%) and anemia (4.3%). The ORR in 4EVER was lower than in BOLERO-2, likely due to inclusion of patients with more advanced disease and extensive pretreatment. These data confirm the clinical benefits and known safety profile of everolimus plus exemestane in postmenopausal women with HR+, HER2− aBC.
CRIS-Team Scopus Importer:2019-06-18
Keywords: advanced breast cancer; estrogen receptor-positive; everolimus; exemestane; HER2-negative

Efficacy and safety of ribociclib (RIB) in combination with letrozole (LET) in patients with estrogen receptorepositive advanced breast cancer (ABC): Secondary and exploratory results of phase 3b RIBECCA study - Decker, T.; Fasching, Peter; Nusch, A.; Hartkopf, A.; Heinrich, B. J.; Kurbacher, C. M.; Fuchs, R.; Tesch, H.; Krabisch, P.; Huober, J.; Kuemmel, S.; Brucker, S. Y.; et al. (ANNALS OF ONCOLOGY, 2021)
CRIS-Team WoS Importer:2021-10-15

Efficacy of Lapatinib in Patients with HER2-Negative Metastatic Breast Cancer and HER2-Positive Circulating Tumor Cells - The DETECT III Clinical Trial - Fehm, Tanja; Mueller, Volkmar; Banys-Paluchowski, Maggie; Fasching, Peter; Friedl, Thomas W.P.; Hartkopf, Andreas; Huober, Jens; Löhberg, Christian; Rack, Brigitte; Riethdorf, Sabine; Schneeweiss, Andreas; Wallwiener, Diethelm; et al. (Clinical Chemistry, 2024)
Background: The phenotypes of tumor cells change during disease progression, but invasive rebiopsies of metastatic lesions are not always feasible. Here we aimed to determine whether initially HER2-negative metastatic breast cancer (MBC) patients with HER2-positive circulating tumor cells (CTCs) benefit from a HER2-targeted therapy. Methods: The open-label, interventional randomized phase III clinical trial (EudraCT Number 2010-024238-46, CliniclTrials.gov Identifier: NCT01619111) recruited from March 2012 until September 2019 with a follow-up duration of 19.5 months. It was a multicenter clinical trial with 94 participating German study centers. A total of 2137 patients with HER2-negative MBC were screened for HER2-positive CTCs with a final modified intention-to-treat population of 101 patients. Eligible patients were randomized to standard therapy with or without lapatinib. Primary study endpoints included CTC clearance (no CTCs at the end of treatment) and secondary endpoints were progression-free survival, overall survival (OS), and safety. Results: In both treatment arms CTC clearance at first follow-up visit - although not being significantly different for both arms at any time point - was significantly associated with improved OS (42.4 vs 14.1 months; P = 0.002). Patients treated additionally with lapatinib had a significantly improved OS over patients receiving standard treatment (20.5 vs 9.1 months, P = 0.009). Conclusions: DETECT III is the first clinical study indicating that phenotyping of CTCs might have clinical utility for stratification of MBC cancer patients to HER2-targeting therapies. The OS benefit could be related to lapatinib, but further studies are required to prove this clinical observation. ClinicalTrials.gov Registration Number: NCT01619111.
CRIS-Team Scopus Importer:2024-01-19

Efficacy of Margetuximab vs Trastuzumab in Patients With Pretreated ERBB2-Positive Advanced Breast Cancer A Phase 3 Randomized Clinical Trial - Rugo, Hope S.; Im, Seock-Ah; Cardoso, Fatima; Cortes, Javier; Curigliano, Giuseppe; Musolino, Antonino; Pegram, Mark D.; Wright, Gail S.; Saura, Cristina; Escriva-De-Romani, Santiago; De Laurentiis, Michelino; Levy, Christelle; et al. (JAMA Oncology, 2021)
IMPORTANCE ERRB2 (formerly HER2)-positive advanced breast cancer (ABC) remains typically incurable with optimal treatment undefined in later lines of therapy. The chimeric antibody margetuximab shares ERBB2 specificity with trastuzumab but incorporates an engineered Fc region to increase immune activation.
CRIS-Team WoS Importer:2021-01-29

Efficacy of neoadjuvant pertuzumab in addition to chemotherapy and trastuzumab in routine clinical treatment of patients with primary breast cancer: a multicentric analysis - Fasching, Peter; Hartkopf, Andreas D.; Gaß, Paul; Häberle, Lothar; Akpolat-Basci, Leyla; Hein, Alexander; Volz, Bernhard; Taran, Florin-Andrei; Nabieva, Naiba; Pott, Birgit; Overkamp, Friedrich; Einarson, Hanna; et al. (Breast Cancer Research and Treatment, 2019)
PurposeNeoadjuvant combination treatment with chemotherapy (CTX), trastuzumab (TZM), and pertuzumab (PTZ) has been shown to result in higher pathological complete response rates (pCR) in comparison with treatment with chemotherapy and trastuzumab (CTX/TZM). This analysis was aimed at real-world validation of these results from prospective randomized trials.MethodsIn a retrospective analysis conducted in the PRAEGNANT network, patients were eligible for inclusion if they had either received neoadjuvant therapy with CTX/TZM or chemotherapy, trastuzumab, and pertuzumab (CTX/TZM/PTZ) and subsequently underwent surgery for their primary breast cancer. The effect of the two neoadjuvant regimens on pCR in addition to commonly applicable predictors of pCR was analyzed in 300 patients from three study sites, using logistic regression analyses with treatment arm, age, clinical tumor stage, grading, and hormone receptor status as predictors.ResultspCR with complete disappearance of all tumor cells was seen in 30.2% (n=58) of patients treated with CTX/TZM and in 52.8% (n=57) of those treated with CTX/TZM/PTZ. CTX/TZM/PTZ was positively associated with pCR (adjusted odds ratio 2.44; 95% CI 1.49-4.02). Mastectomy rates were not influenced by the therapy.ConclusionsThe results of clinical trials were confirmed in this dataset of patients who were treated outside of clinical trials in everyday routine work. pCR rates can be improved by 20% with pertuzumab in routine clinical use.
CRIS-Team WoS Importer:2019-03-15

Efficacy of the tyrosine kinase inhibitor lapatinib in the treatment of patients with HER2-negative metastatic breast cancer and HER2-positive circulating tumor cells - results from the randomized phase III DETECT III trial - Fehm, Tanja; Mueller, Volkmar; Banys-Paluchowski, Maggie; Fasching, Peter; Friedl, Thomas W. P.; Hartkopf, Andreas; Huober, Jens; Loehberg, Christian; Rack, Brigitte; Riethdorf, Sabine; Schneeweiss, Andreas; Wallwiener, Diethelm; et al. (CANCER RESEARCH, 2021)
CRIS-Team WoS Importer:2021-03-26

Efficacy, safety, and prognosis prediction in patients treated with ribociclib in combination with letrozole: Final results of phase 3b RIBECCA study in hormone receptor positive, human epidermal growth factor receptor-2 negative, locally advanced or metastatic breast cancer - Fasching, Peter; Decker, Thomas; Hartkopf, Andreas; Nusch, Arnd; Heinrich, Bernhard J.; Kurbacher, Christian; Fuchs, Roswitha; Tesch, Hans; Krabisch, Petra; Huober, Jens; Kuemmel, Sherko; Brucker, Sara; et al. (European Journal of Cancer, 2024)
Background: In MONALEESA-2, addition of ribociclib to letrozole resulted in significantly longer progression-free survival (PFS) in postmenopausal women with HR+HER2− advanced breast cancer (ABC). RIBociclib for the treatment of advanCed breast CAncer (RIBECCA) study investigated ribociclib plus letrozole in a patient population reflecting routine clinical practice. Patients and methods: In this multicenter, open-label, single-arm, phase 3b study, patients with HR+HER2− ABC not amenable to curative therapy and ECOG performance status ≤ 2 received ribociclib plus letrozole (cohort A: postmenopausal women and men in first-line; cohort B: pre-/perimenopausal women in first-line [B1], patients pretreated for advanced disease [B2]). The primary endpoint was clinical benefit rate (CBR) by week 24; secondary endpoints included overall response rate (ORR), PFS, overall survival (OS), and safety. Association of patient and tumor characteristics with PFS was analyzed by multivariable Cox regression analysis. Results: Overall, 487 patients were evaluable for efficacy, 502 for safety. By week 24, CBR was 60.8 % (95 % CI, 56.3–65.1), ORR was 19.3 % (95 % CI, 15.9–23.1). Median PFS was 21.8 months (95 % CI, 13.9–25.3) in first-line postmenopausal patients and 11.0 months (95 % CI, 8.2–16.4) in premenopausal and pretreated patients. Median OS was not reached. Higher baseline ECOG performance status, higher histological grade, and negative progesterone receptor status showed an unfavorable effect on PFS. Most common adverse events were neutropenia (50.0 %), nausea (42.0 %), and fatigue (39.2 %). Conclusion: In this broad population of patients with HR+HER2− ABC, efficacy and safety results of ribociclib plus letrozole were similar to those observed in pivotal trials.
CRIS-Team Scopus Importer:2024-02-02
Keywords: Advanced breast cancer; CDK4/6 inhibitor; Letrozole; RIBECCA; Ribociclib

Einfluss der COVID-19 Pandemie auf die Leistungszahlen eines universitären und zertifizierten Kontinenz- und Beckenbodenzentrums - Heindl, Felix; Winkler, M.; Schreiter, S.; Born, Tilman; Füller, Andreas; Schulmeyer, Carla; Beckmann, Matthias; Burghaus, Stefanie; Becker, Karina (GEBURTSHILFE UND FRAUENHEILKUNDE, 2022)
CRIS-Team WoS Importer:2022-11-04

Elective gynaecological operations during sars-cov-2-pandemic. Durchführung von elektiven und benignen gynäkologischen operationen während der sars-cov-2-pandemie - Burghaus, Stefanie; Beckmann, Matthias; Hein, Alexander (Journal für Reproduktionsmedizin und Endokrinologie, 2021)
The SARS-CoV-2-pandemic led to a request in March 2020 for hospitals to postpone all medically not urgent operations, thus freeing up treatment and intensive care capacities. In gynaecology, this has particularly affected patients undergoing reproductive medical treatment, as well as patients with benign gynaecological diseases such as endome-triosis and uterine fibroids. The present study is intended to show how surgical interventions can be carried out during the SARS-CoV-2 pandemic, taking into account staff and patient safety, and what measures must be undertaken to do so. J Reproduktionsmed Endokrinol 2021; 18 (1): 8–12.
CRIS-Team Scopus Importer:2021-05-28
Keywords: COVID-19; Elective surgery; Gynaecology; SARS-CoV-2

Electronic-Based Patient-Reported Outcomes: Willingness, Needs, and Barriers in Adjuvant and Metastatic Breast Cancer Patients - Hartkopf, Andreas D.; Graf, Joachim; Simoes, Elisabeth; Keilmann, Lucia; Sickenberger, Nina; Gaß, Paul; Wallwiener, Diethelm; Matthies, Lina; Taran, Florin-Andrei; Lux, Michael P.; Wallwiener, Stephanie; Belleville, Eric; et al. (JMIR Cancer, 2017)
BACKGROUND: Patient-reported outcomes (PROs) play an increasingly important role as an adjunct to clinical outcome parameters in measuring health-related quality of life (HRQoL). In fact, PROs are already the accepted gold standard for collecting data about patients' subjective perception of their own state of health. Currently, paper-based surveys of PRO still predominate; however, knowledge regarding the feasibility of and barriers to electronic-based PRO (ePRO) acceptance remains limited. OBJECTIVE: The objective of this trial was to analyze the willingness, specific needs, and barriers of adjuvant breast cancer (aBC) and metastatic breast cancer (mBC) patients in nonexposed (no exposure to electronic assessment) and exposed (after exposure to electronic assessment decision, whether a tablet-based questionnaire is favored) settings before implementing digital ePRO assessment in relation to health status. We also investigated whether providing support can increase the patients' willingness to participate in such programs. METHODS: The nonexposed patients only answered a paper-based questionnaire, whereas the exposed patients filled out both paper- and tablet-based questionnaires. The assessment comprised socioeconomic variables, HRQoL, preexisting technical skills, general attitude toward electronic-based surveys, and potential barriers in relation to health status. Furthermore, nonexposed patients were asked about the existing need for technological support structures. In the course of data evaluation, we performed a frequency analysis as well as chi-square tests and Wilcoxon signed-rank tests. Subsequently, relative risks analysis, univariate categorical regression (CATREG), and mediation analyses (Hayes' bias-corrected bootstrap) were performed. RESULTS: A total of 202 female breast cancer patients completed the PRO assessment (nonexposed group: n=96 patients; exposed group: n=106 patients). Self-reported technical skills were higher in exposed patients (2.79 vs 2.33, P ≤.001). Significant differences were found in relation to willingness to use ePRO (92.3% in the exposed group vs 59% in the nonexposed group; P=.001). Multiple barriers were identified, and most of them showed statistically significant differences in favor of the exposed patients (ie, data security [13% in the exposed patients vs 30% in the nonexposed patients; P=.003] and no prior technology usage [5% in the exposed group vs 15% in the nonexposed group; P=.02]), whereas the differences in disease burden (somatic dimension: 4% in the exposed group vs 9% in the nonexposed group; P=.13) showed no significance. In nonexposed patients, requests for support services were identified, which could increase their ePRO willingness. CONCLUSIONS: Significant barriers in relation to HRQoL, cancer-related restrictions, and especially the setting of the survey were identified in this trial. Thus, it is necessary to address and eliminate these barriers to ensure data accuracy and reliability for future ePRO assessments. Exposure seems to be a potential option to increase willingness to use ePRO and to reduce barriers.
EVALuna2:36440

Electrospun patterned porous scaffolds for the support of ovarian follicles growth: a feasibility study - Liverani, Liliana; Amir, Fattahi; Raffel, Nathalie; Preis, Alexander; Hoffmann, Inge; Boccaccini, Aldo R.; Beckmann, Matthias; Dittrich, Ralf (Scientific Reports, 2019)
Recently, the interest of the scientific community is focused on the application of tissue engineering approach for the fertility restoration. In this paper innovative patterned electrospun fibrous scaffolds were fabricated and used as 3D system for porcine follicles culture. The obtained scaffolds demonstrated to be a suitable support which did not alter or interfere with the typical spherical follicles morphology. The fibrillar structure of the scaffolds mimics the morphology of the healthy native tissue. The use of porcine follicles implied many advantages respect to the use of mouse model. Relevant results showed that more than the scaffold pattern and struts dimension, the selection of proper biomaterials improve the follicles adhesion and development.
CRIS-Team WoS Importer:2019-02-21

ELECTROSPUN SCAFFOLDS FOR OVARIAN TISSUE ENGINEERING: KEY POINTS OF SCAFFOLD-FOLLICLES INTERACTIONS - Liverani, Liliana; Bleisinger, Nathalie; Hoffmann, Inge; Beckmann, Matthias; Dittrich, Ralf; Boccaccini, Aldo R. (TISSUE ENGINEERING PART A, 2022)
CRIS-Team WoS Importer:2022-08-12