Replies - Letter to the Editor - “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, D.; Günther, J.; Schederecker, F.; Donik, L.; Meyer, D.; Hermsdörfer, J.; Friedl, T. W.P.; Rack, B.; Beckmann, Matthias; Janni, W.; Hauner, H. (Clinical Nutrition, 2024)
CRIS-Team Scopus Importer:2024-11-15
Keywords: Breast cancer; Lifestyle intervention; Nutrition

Reply to "Response to: Dittrich et al.: Non-Embryo-Destructive Extraction of Pluripotent Embryonic Stem Cells - Overlooked Legal Prohibitions, Professional Legal Consequences and Inconsistencies in Patent Law" - Dittrich, Ralf; Beckmann, Matthias; Wuerfel, W. (Geburtshilfe und Frauenheilkunde, 2016)
EVALuna2:32938

Reproducibility of mRNA-Based Testing of ESR1, PGR, ERBB2, and MKI67 Expression in Invasive Breast Cancer-A Europe-Wide External Quality Assessment - Erber, Ramona; Hartmann, Arndt; Fasching, Peter; Rübner, Matthias; Stöhr, Robert; Beckmann, Matthias; Zentgraf, Miriam; Popp, Verena; Weidler, Jodi; Simon, Iris; Becker, Steffi; Hübner, Hanna; et al. (Cancers, 2021)
Simple Summary Four biomarkers [estrogen receptor (ER), progesterone receptor (PgR), Ki-67, and HER2], are used to stratify breast cancer (BC) into subtypes predictive of therapy response. In a Europe-wide external quality assessment, we compared performance of an mRNA-based method [Xpert(R) Breast Cancer STRAT4 (CE-IVD)] for determining ESR1, PGR, ERBB2, and MKI67 expression against the gold standard [immunohistochemistry (IHC)/HER2 in situ hybridization (ISH)]. The coordinating center (CC) and five European laboratories tested ten breast cancer samples. STRAT4 binary (positive or negative) results of each marker were compared with the gold standard. ESR1 and ERBB2 mRNA results were concordant with IHC/ISH in all single analyses. In contrast, PGR and MKI67 results were discordant in a few cases, which had STRAT4 expression values close to assay cut-offs and immunohistochemically presented heterogeneous low positive PgR and heterogeneous Ki-67. STRAT4 assay may be a reproducible method. However, cases with expression values close to cut-offs should be carefully reviewed. Estrogen receptor (ER), progesterone receptor (PgR), Ki-67, and HER2 immunohistochemistry (IHC) together with HER2 in situ hybridization (ISH) are utilized to classify invasive breast cancer (IBC) into predictive molecular subtypes. As IHC evaluation may be hampered by analytical errors, gene expression assays could offer a reliable alternative. In this first Europe-wide external quality assessment (EQA) study, we investigated performance of mRNA-based Xpert(R) Breast Cancer STRAT4 (CE-IVD) in five European laboratories. The cohort comprised ten pre-therapy IBC core biopsies diagnosed in the coordinating center (CC). STRAT4 binary (positive or negative) mRNA results of each marker (ESR1, PGR, ERBB2, MKI67) were compared with the gold standard IHC/ISH performed by the CC. Sensitivity, specificity, and accuracy of ESR1 and ERBB2 mRNA were 100% for all samples. In contrast, PGR expression was falsely negative for one case by two sites and MKI67 falsely negative for two cases (respectively by four and one sites). These cases had STRAT4 expression values close to assay cut-offs and immunohistochemically presented heterogeneous low positive PgR and heterogeneous Ki-67. Our EQA shows that STRAT4 mRNA assay may be a reproducible method to evaluate ER, PgR, HER2, and Ki-67 status. However, cases with expression values close to assay cut-offs should be carefully reviewed.
CRIS-Team WoS Importer:2021-10-08

Reproductive profiles and risk of breast cancer subtypes: a multi-center case-only study - Brouckaert, Olivier; Rudolph, Anja; Laenen, Annouschka; Keeman, Renske; Bolla, Manjeet K.; Wang, Qin; Soubry, Adelheid; Wildiers, Hans; Andrulis, Irene L.; Arndt, Volker; Beckmann, Matthias; Benitez, Javier; et al. (Breast Cancer Research, 2017)
BACKGROUND: Previous studies have shown that reproductive factors are differentially associated with breast cancer (BC) risk by subtypes. The aim of this study was to investigate associations between reproductive factors and BC subtypes, and whether these vary by age at diagnosis. METHODS: We used pooled data on tumor markers (estrogen and progesterone receptor, human epidermal growth factor receptor-2 (HER2)) and reproductive risk factors (parity, age at first full-time pregnancy (FFTP) and age at menarche) from 28,095 patients with invasive BC from 34 studies participating in the Breast Cancer Association Consortium (BCAC). In a case-only analysis, we used logistic regression to assess associations between reproductive factors and BC subtype compared to luminal A tumors as a reference. The interaction between age and parity in BC subtype risk was also tested, across all ages and, because age was modeled non-linearly, specifically at ages 35, 55 and 75 years. RESULTS: Parous women were more likely to be diagnosed with triple negative BC (TNBC) than with luminal A BC, irrespective of age (OR for parity = 1.38, 95% CI 1.16-1.65, p = 0.0004; p for interaction with age = 0.076). Parous women were also more likely to be diagnosed with luminal and non-luminal HER2-like BCs and this effect was slightly more pronounced at an early age (p for interaction with age = 0.037 and 0.030, respectively). For instance, women diagnosed at age 35 were 1.48 (CI 1.01-2.16) more likely to have luminal HER2-like BC than luminal A BC, while this association was not significant at age 75 (OR = 0.72, CI 0.45-1.14). While age at menarche was not significantly associated with BC subtype, increasing age at FFTP was non-linearly associated with TNBC relative to luminal A BC. An age at FFTP of 25 versus 20 years lowered the risk for TNBC (OR = 0.78, CI 0.70-0.88, p < 0.0001), but this effect was not apparent at a later FFTP. CONCLUSIONS: Our main findings suggest that parity is associated with TNBC across all ages at BC diagnosis, whereas the association with luminal HER2-like BC was present only for early onset BC.
EVALuna2:36119

Resilience, Fear of Progression and Psychosocial Distress in Patients with Breast Cancer and Gynecological Tumors Seeking a Second Opinion. - Krebs, Jessica; Wasner, Sonja; Egloffstein, Sainab; Lux, Michael P.; Morawa, Eva; Beckmann, Matthias; Erim, Yesim (Psychotherapie Psychosomatik Medizinische Psychologie, 2018)

Response and prognosis after neoadjuvant chemotherapy in 1,051 patients with infiltrating lobular breast carcinoma - Loibl, Sibylle; Volz, Cristina; Mau, Christine; Blohmer, Jens-Uwe; Costa, Serban D.; Eidtmann, Holger; Fasching, Peter; Gerber, Bernd; Hanusch, Claus; Jackisch, Christian; Kuemmel, Sherko; Huober, Jens; et al. (Breast Cancer Research and Treatment, 2014)
Invasive lobular carcinomas (ILC) show better clinical behaviour compared with other histological types, but significantly lower pathological complete response (pCR) rates after neoadjuvant chemotherapy (NACT). We investigated whether factors influencing pCR rate in ILC after NACT can be identified and whether clinical outcome is different. 9,020 breast cancer patients from nine German neoadjuvant trials with known histological type were pooled. 11.7 % of tumours were ILC. Endpoints were: pCR rate, surgery type and survival. ILC was associated with older age, larger tumour size, lymph node negativity, lower grade and positive hormone-receptor-status (HR). Patients with ILC achieved a significantly lower pCR rate compared with non-ILC patients (6.2 vs. 17.4 %, P < 0.001). The pCR rate was 4.2 % in ILC/HR+/G1-2, 7.0 % in ILC with either HR- or G3, and 17.8 % in ILC/HR-/G3. Mastectomy rate was higher in ILC compared with non-ILC patients irrespective of response to NACT (pCR: 27.4 vs. 16.6 %, P = 0.037 and non-pCR: 41.8 % vs. 31.5 %, P < 0.0001). Age and HR independently predicted pCR in ILC. In ILC patients, pCR did not predict distant disease free (DDFS) and loco-regional disease free survival (LRFS), but overall survival (OS). Non-pCR patients with ILC had significantly better DDFS (P = 0.018), LRFS (P < 0.0001) and OS (P = 0.044) compared with non-ILC patients. Patients with ILC had a low chance of obtaining a pCR and this is not well correlated with further outcome. The mastectomy rate was considerably high in ILC patients even after obtaining a pCR. We, therefore, suggest to offer NACT mainly to ILC patients with HR-negative tumours.
EVALuna2:17507

Response to di Cosimo, Torri, and Porcu - Trapp, Elisabeth; Janni, Wolfgang; Schindlbeck, Christian; Jückstock, Julia; Andergassen, Ulrich; Degregorio, Amelie; Alunni-Fabbroni, Marianna; Tzschaschel, Marie; Polasik, Arkadius; Koch, Julian G.; Friedl, Thomas W.P.; Fasching, Peter A.; et al. (Journal of the National Cancer Institute, 2019)
CRIS-Team Scopus Importer:2019-12-24

Response to "Letter to the Editor" by Federico Prefumo - Stumpfe, Florian M.; Faschingbauer, Florian (Archives of Gynecology and Obstetrics, 2019)
CRIS-Team WoS Importer:2019-11-22

Response to "screening depression during and after pregnancy using the EPDS" - Hein, Alexander; Fasching, Peter; Goecke, Tamme W. (Archives of Gynecology and Obstetrics, 2014)
EVALuna2:17514

Responsiveness of human neonates to the odor of 5alpha-androst-16-en-3-one: A behavorial paradox? - Loos, Helene; Doucet, Sèbastien; Soussignan, Robert; Hartmann, Constanze; Durand, Karine; Dittrich, Ralf; Sagot, Paul; Büttner, Andrea; Schaal, Benoist (Chemical Senses, 2014)
The odorous steroid 5α-androst-16-en-3-one (AND) occurs in numerous biological fluids in mammals, including man, where it is believed to play a chemocommunicative role. As AND was recently detected in milk and amniotic fluid, sensitivity and hedonic responses to this substance were assessed in human neonates. To this aim, respiration and facial expressions were recorded in 3-day-old newborns in response to aqueous solutions of AND, ranging from 500ng/mL to 0.5 fg/mL. Although analyses of respiratory rate did not lead to clear-cut results, the newborns changed their facial expressions at concentrations not detected by adults in a triangle test. Newborns displayed negative facial actions of longer duration to AND relative to an odorless control. Thus, AND may be considered to be offensive to newborns, which is a counterintuitive outcome as they are exposed to this compound in the womb (and it should therefore be familiar), in milk, and on the mother’s skin surface (and it should therefore be conditioned as positive). Multiple reasons for this perceptual-behavioral paradox are discusse
UnivIS-Import:2015-04-14:Pub.2014.nat.dchph.llmch.respon
Keywords: Amniotic fluid; Androstenone; Aversion; Milk; Olfaction

Responsiveness of human neonates to the odor of 5α-androst-16-en-3-one: A behavioral paradox? - Loos, Helene M.; Doucet, Sèbastien; Soussignan, Robert; Hartmann, Constanze; Durand, Karine; Dittrich, Ralf; Sagot, Paul; Büttner, Andrea; Schaal, Benoist (Chemical Senses, 2014)
The odorous steroid 5α-androst-16-en-3-one (AND) occurs in numerous biological fluids in mammals, including man, where it is believed to play a chemocommunicative role. As AND was recently detected in milk and amniotic fluid, sensitivity and hedonic responses to this substance were assessed in human neonates. To this aim, respiration and facial expressions were recorded in 3-day-old newborns in response to aqueous solutions of AND, ranging from 500ng/mL to 0.5 fg/mL. Although analyses of respiratory rate did not lead to clear-cut results, the newborns changed their facial expressions at concentrations not detected by adults in a triangle test. Newborns displayed negative facial actions of longer duration to AND relative to an odorless control. Thus, AND may be considered to be offensive to newborns, which is a counterintuitive outcome as they are exposed to this compound in the womb (and it should therefore be familiar), in milk, and on the mother's skin surface (and it should therefore be conditioned as positive). Multiple reasons for this perceptual-behavioral paradox are discussed.<br

Results from CONTESSA: A phase 3 study of tesetaxel plus a reduced dose of capecitabine versus capecitabine alone in patients with HER2-, hormone receptor plus (HR plus ) metastatic breast cancer (MBC) who have previously received a taxane - O'Shaughnessy, Joyce; Schwartzberg, Lee; Piccart, Martine; Rugo, Hope S.; Yardley, Denise A.; Cortes, Javier; Untch, Michael; Harbeck, Nadia; Wright, Gail S.; Bondarenko, Igor; Glaspy, John; Nowecki, Zbigniew; et al. (CANCER RESEARCH, 2021)
CRIS-Team WoS Importer:2021-03-26

Results of ovulation induction with pulsatile GnRH using a novel portable device (LutrePulse (R)) - Hildebrandt, T.; Bartnitzky, S.; Bauer, K.; Boppert, H.; Luckhaus, J.; Ristau, B. (2017)
EVALuna2:36174

Results of Stimulation Treatment through pulsatile GnRH Substitution by using an innovative, patient-controlled System (LutrePulse((R))) - Hildebrandt, Thomas; Lotz, Laura; Blum, Simon; Fahlbusch, C.; Heusinger, K.; Cupisti, S.; Dittrich, Ralf; Beckmann, Matthias; Antoniadis, Sophia (GEBURTSHILFE UND FRAUENHEILKUNDE, 2020)
CRIS-Team WoS Importer:2020-10-30

Results of TRIO-14, a phase II, multicenter, randomized, placebo-controlled trial of carboplatin-paclitaxel versus carboplatin-paclitaxel-ganitumab in newly diagnosed epithelial ovarian cancer - Konecny, G. E.; Hendrickson, A. E.Wahner; Davidson, T. M.; Winterhoff, B. J.; Ma, S.; Mahner, S.; Sehouli, J.; Fasching, Peter; Feisel-Schwickardi, G.; Poelcher, M.; Roman, L. D.; Rody, A.; et al. (Gynecologic Oncology, 2021)
Purpose: Insulin-like growth factor (IGF) signaling is implicated in pathogenesis and chemotherapy resistance of epithelial ovarian cancer (EOC). We explored efficacy and safety of adding ganitumab, a monoclonal antibody targeting IGF-1R, to carboplatin/paclitaxel (CP) chemotherapy in patients with primary EOC. Design: Patients were randomly assigned to receive CP/ganitumab (18 mg/kg q3w) or CP/placebo for 6 cycles followed by 6 cycles of single agent ganitumab/placebo maintenance therapy as front-line therapy. Primary endpoint was progression free survival. Secondary endpoints were time to progression and overall survival. Pretreatment samples were prospectively collected for retrospective biomarker analyses. Results: 170 patients enrolled. 165 patients assessable for toxicity. Median PFS was 15.7 months with CP/ganitumab and 16.7 months with CP/placebo (HR 1.23; 95% CI 0.82–1.83, P = 0.313). All grade neutropenia (84.1% vs 71.4%), thrombocytopenia (75.3% vs 57.1%) and hyperglycemia (15.9% vs 2.6%) were more common in the ganitumab group compared to the placebo group. Ganitumab/placebo related serious adverse events were reported in 26.1% of the patients with ganitumab and in 6.5% with placebo. Non-progression related fatal events were more common with ganitumab (5 versus 2 patients). The ganitumab group experienced more dose delays which resulted in lower relative dose intensity of chemotherapy in the experimental group. In an exploratory model IGFBP2 expression was predictive of ganitumab response (treatment interaction; PFS, P = 0.03; OS, P = 0.01). Conclusion: Addition of ganitumab to CP chemotherapy in primary EOC did not improve PFS. Our results do not support further study of ganitumab in unselected EOC patients.
CRIS-Team Scopus Importer:2021-10-22
Keywords: Ganitumab; IGFR1 inhibitor; Insulin-like growth factor; Ovarian cancer; Targeted therapy

Retraction: Improving usability and pregnancy rates of a fertility monitor by an additional mobile application: Results of a retrospective efficacy study of Daysy and DaysyView app (Reproductive Health (2018)15 (37) DOI: 10.1186/s12978-018-0479-6) - 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; Pöhls, Uwe G.; et al. (Reproductive Health, 2019)
The Editor-in-Chief is retracting this article [1]. After publication concerns were raised about the reliability of the estimates of contraceptive effectiveness for the Daysy device when being used together with the DaysyView app [2]. Independent post-publication peer review has confirmed that there are fundamental flaws in the methodology which mean that the conclusions are unreliable due to selection bias and the retrospective self-reporting of whether pregnancies were intentional. The authors do not agree with this retraction. In particular, the authors are of the opinion that the retrospective design of their underlying study is described and that the respective disadvantages are discussed transparently in this article.
CRIS-Team Scopus Importer:2019-05-28

Return of individual genomic research results within the PRAEGNANT multicenter registry study - Hübner, Hanna; Rübner, Matthias; Kurbacher, Christian; Hadji, Peyman; Hartkopf, Andreas D.; Lux, Michael P.; Huober, Jens; Uhrig, Sabrina; Taran, Florin Andrei; Overkamp, Friedrich; Tesch, Hans; Häberle, Lothar; et al. (Breast Cancer Research and Treatment, 2022)
Purpose: The PRAEGNANT study is a registry study for metastatic breast cancer patients, focusing on biomarker detection. Recently, within this study, genetic alterations in 37 breast cancer predisposition genes were analyzed and genetic findings were detected for 396 participants. The aim of this project was to return genetic results to the physicians and to analyze actions taken (e.g., disclosure of results to patients, validation of results, clinical impact, and impact on the patient’s quality of life) using a questionnaire. Methods: 235 questionnaires were sent out to the study centers, with each questionnaire representing one patient with a genetic finding. The questionnaire consisted of twelve questions in the German language, referring to the disclosure of results, validation of test results, and their impact on treatment decisions and on the patient’s quality of life. Results: 135 (57.5%) questionnaires were completed. Of these, 46 (34.1%) stated that results were returned to the patients. In 80.0% (N = 36) of cases where results were returned, the patient had not been aware of the finding previously. For 27 patients (64.3%), genetic findings had not been validated beforehand. All validation procedures (N = 15) were covered by the patients’ health insurance. For 11 (25.0%) patients, physicians reported that the research results influenced current or future decision-making on treatment, and for 37.8% (N = 17) the results influenced whether family members will be genetically tested. Conclusion: This study provides novel insights into the return of research results and into clinical and personal benefits of disclosure of genetic findings within a German registry.
CRIS-Team Scopus Importer:2022-12-02
Keywords: Breast cancer; Genetic testing; Incidental findings; Research results; Return of results

Revised German guidelines on the diagnosis and treatment of carcinoma of the uterine cervix-what's new for pathologists in 2021? - Horn, Lars-Christian; Beckmann, Matthias; Follmann, Markus; Koch, Martin C.; Nothacker, Monika; Poschel, Birgit; Stübs, Frederik; Schmidt, Dietmar; Hohn, Anne Kathrin (Pathologe, 2022)
In 2021, the 2015 German consensus guideline for the diagnosis and treatment of uterine cervical carcinoma was updated. The present article summarises the new recommendations for pathologists: the incorporation of the International Endocervical Adenocarcinoma Classification (IECC), which morphologically separates HPV-associated and non-HPV-associated adenocarcinomas, as well as the reporting of the prognostic relevant growth pattern of the adenocarcinoma of the endocervical subtype (Silva pattern). Histologically, multifocality has been defined as the presence of clearly invasive foci with a minimum distance between each focus of 0.2 cm. Because of its intratumoural heterogeneity, all carcinomas <= 2 cm in their largest dimension should be processed completely, and tumours > 2 cm should be processed with one block per centimetre of their greatest dimension. In cases of (radical) trachelectomy/hysterectomy, the distal vaginal resection margin and all parametrial tissue should be processed completely. Sentinel lymph nodes have to be processed completely by lamellation along its long axis in 0.2 cm intervals. Immunohistochemical ultrastaging is mandatory. Staging should be performed using the 2009 FIGO classification and 2017 TNM classification. Reporting the revised 2018 FIGO classification is optional. To date, molecular markers have not been relevant for prognostication and treatment decision making.
CRIS-Team WoS Importer:2022-03-04
Keywords: Cutting; Workup; Diagnostic

Ribecca - a phase 3b, multi-center, open label study for women with estrogen receptor positive, locally advanced or metastatic breast cancer treated with ribociclib (lee011) in combination with letrozole: Final results - Reinisch, Mattea; Nusch, Arndt; Decker, Thomas; Hartkopf, Andreas; Heinrich, Bernhard J.; Kurbacher, Christian M.; Fuchs, Roswitha; Tesch, Hans; Krabisch, Petra; Brucker, Sara Y.; Fehm, Tanja; Janni, Wolfgang; et al. (CANCER RESEARCH, 2021)
CRIS-Team WoS Importer:2021-03-26

Ribociclib plus Endocrine Therapy in Early Breast Cancer - Slamon, Dennis; Lipatov, Oleg; Nowecki, Zbigniew; McAndrew, Nicholas; Kukielka-Budny, Bozena; Stroyakovskiy, Daniil; Yardley, Denise A.; Huang, Chiun Sheng; Fasching, Peter; Crown, John; Bardia, Aditya; Chia, Stephen; et al. (New England Journal of Medicine, 2024)
Background Ribociclib has been shown to have a significant overall survival benefit in patients with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer. Whether this benefit in advanced breast cancer extends to early breast cancer is unclear. Methods In this international, open-label, randomized, phase 3 trial, we randomly assigned patients with HR-positive, HER2-negative early breast cancer in a 1:1 ratio to receive ribociclib (at a dose of 400 mg per day for 3 weeks, followed by 1 week off, for 3 years) plus a nonsteroidal aromatase inhibitor (NSAI; letrozole at a dose of 2.5 mg per day or anastrozole at a dose of 1 mg per day for ≥5 years) or an NSAI alone. Premenopausal women and men also received goserelin every 28 days. Eligible patients had anatomical stage II or III breast cancer. Here we report the results of a prespecified interim analysis of invasive disease-free survival, the primary end point; other efficacy and safety results are also reported. Invasive disease-free survival was evaluated with the use of the Kaplan-Meier method. The statistical comparison was made with the use of a stratified log-rank test, with a protocol-specified stopping boundary of a one-sided P-value threshold of 0.0128 for superior efficacy. Results As of the data-cutoff date for this prespecified interim analysis (January 11, 2023), a total of 426 patients had had invasive disease, recurrence, or death. A significant invasive disease-free survival benefit was seen with ribociclib plus an NSAI as compared with an NSAI alone. At 3 years, invasive disease-free survival was 90.4% with ribociclib plus an NSAI and 87.1% with an NSAI alone (hazard ratio for invasive disease, recurrence, or death, 0.75; 95% confidence interval, 0.62 to 0.91; P=0.003). Secondary end points - distant disease-free survival and recurrence-free survival - also favored ribociclib plus an NSAI. The 3-year regimen of ribociclib at a 400-mg starting dose plus an NSAI was not associated with any new safety signals. Conclusions Ribociclib plus an NSAI significantly improved invasive disease-free survival among patients with HR-positive, HER2-negative stage II or III early breast cancer. (Funded by Novartis; NATALEE ClinicalTrials.gov number, NCT03701334.)
CRIS-Team Scopus Importer:2024-04-12
Keywords: Breast Cancer; Hematology/Oncology; Treatments in Oncology

Ribociclib plus fulvestrant for advanced breast cancer: Health-related quality-of-life analyses from the MONALEESA-3 study - Fasching, Peter; Beck, J. Thaddeus; Chan, Arlene; De Laurentiis, Michele; Esteva, Francisco J.; Jerusalem, Guy; Neven, Patrick; Pivot, Xavier; Bianchi, Giulia V.; Martin, Miguel; Chandiwana, David; Lanoue, Brad; et al. (BREAST, 2020)
Purpose: In the MONALEESA-3 Phase III trial of patients with hormone receptor–positive human epidermal growth factor receptor–negative advanced breast cancer, ribociclib plus fulvestrant significantly improved progression-free survival (PFS) and overall survival (OS). Here, we present patient-reported outcomes from the trial, including health-related quality of life (HRQOL). Methods: Patients were randomized (2:1) to receive ribociclib plus fulvestrant or placebo plus fulvestrant. Time to definitive 10% deterioration (TTD) from baseline in HRQOL (global health status [GHS] from the EORTC QLQ-C30 questionnaire) and pain (BPI-SF questionnaire) were assessed using Kaplan-Meier estimates; a stratified Cox regression model was used to estimate the hazard ratio (HR) and 95% CIs. Results: Deterioration ≥10% in the EORTC-QLQ-C30 GHS was observed in 33% of patients in the ribociclib group vs 34% of patients in the placebo (reference) group (HR for TTD ≥ 10% = 0.81 [95% CI, 0.62–1.1]). Similar findings were noted for TTD ≥5% (HR = 0.79 [95% CI, 0.61–1.0]) and TTD ≥15% (HR = 0.81 [95% CI, 0.60–1.08]). TTD ≥10% in emotional functioning (HR = 0.76 [95% CI, 0.57–1.01]) trended in favor of the ribociclib group, whereas results for fatigue and pain were similar between arms. TTD ≥10% in BPI-SF pain severity index score (HR = 0.77 [95% CI, 0.57–1.05]) and worst pain item score (HR = 0.81 [95% CI, 0.58–1.12]) trended in favor of ribociclib vs placebo. Conclusions: In addition to significantly prolonging PFS and OS compared with placebo plus fulvestrant, adding ribociclib to fulvestrant maintains HRQOL.
CRIS-Team Scopus Importer:2020-10-23
Keywords: Breast cancer; Metastatic; Patient-reported outcomes; Quality of life

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 - 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)
Background: Ribociclib plus fulvestrant demonstrated significant progression-free survival (PFS) and overall survival (OS) benefits in patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative (HR+/HER2−) advanced breast cancer (ABC). Here we present a new landmark in survival follow-up for a phase III cyclin-dependent kinases 4 and 6 inhibitor clinical trial in patients with ABC (median, 56.3 months). Patients and methods: This phase III, randomized, double-blind, placebo-controlled trial was conducted at 174 sites (30 countries). Patients were men and postmenopausal women (age ≥18 years) with histologically/cytologically confirmed HR+/HER2− ABC. Patients could have received ≤1 line of endocrine therapy (ET) but no chemotherapy for ABC. Patients, assigned 2:1, were stratified by the presence/absence of liver/lung metastases and previous ET. Patients received intramuscular fulvestrant (500 mg, day 1 of each 28-day cycle plus day 15 of cycle 1) with oral ribociclib (600 mg/day, 3 weeks on, 1 week off) or placebo. Efficacy analyses were by intention to treat. Safety was assessed in patients receiving ≥1 dose study treatment. OS was a secondary endpoint. MONALEESA-3 is registered with ClinicalTrials.gov (NCT02422615; no longer enrolling). Results: Between 18 June 2015 and 10 June 2016, 726 patients were randomly assigned (484, ribociclib; 242, placebo). At data cut-off (30 October 2020), median OS (mOS) was 53.7 months (ribociclib) versus 41.5 months (placebo) [hazard ratio (HR), 0.73; 95% confidence interval (CI) 0.59-0.90]. Subgroup analyses were consistent with overall population. In the first-line setting, most patients in the ribociclib arm (∼60%) lived longer than median follow-up; mOS was 51.8 months in the placebo arm (HR, 0.64; 95% CI 0.46-0.88). In the second-line setting, mOS was 39.7 months (ribociclib) versus 33.7 months (placebo) (HR, 0.78; 95% CI 0.59-1.04). No apparent drug–drug interaction between ribociclib and fulvestrant or new safety signals were observed. Conclusions: This analysis reported extended OS follow-up in MONALEESA-3. mOS was ∼12 months longer in patients with HR+/HER2− ABC treated with ribociclib plus fulvestrant compared with fulvestrant monotherapy.
CRIS-Team Scopus Importer:2021-08-06
Keywords: advanced breast cancer; CDK4/6 inhibitor; overall survival; ribociclib

Risk factors for locoregional recurrence (LRR) after neoadjuvant chemotherapy: Pooled analysis of prospective neoadjuvant breast cancer (BC) trials - Werutsky, G.; Untch, M.; Hanusch, C.; Fasching, Peter; Blohmer, J. -U.; Seiler, S.; Denkert, C.; Tesch, H.; Jackisch, C.; Gerber, B.; Schneeweiss, A.; Link, T.; et al. (ANNALS OF ONCOLOGY, 2019)
CRIS-Team WoS Importer:2019-11-08

Risk of Ovarian Cancer and the NF-?B Pathway: Genetic Association with IL1A and TNFSF10 - Charbonneau, Bridget; Block, Matthew S.; Bamlet, William R.; Vierkant, Robert A.; Kalli, Kimberly R.; Fogarty, Zachary; Rider, David N.; Sellers, Thomas A.; Tworoger, Shelley S.; Poole, Elizabeth; Risch, Harvey A.; Salvesen, Helga B.; et al. (Cancer Research, 2014)
A missense single-nucleotide polymorphism (SNP) in the immune modulatory gene IL1A has been associated with ovarian cancer risk (rs17561). Although the exact mechanism through which this SNP alters risk of ovarian cancer is not clearly understood, rs17561 has also been associated with risk of endometriosis, an epidemiologic risk factor for ovarian cancer. Interleukin-1? (IL1A) is both regulated by and able to activate NF-?B, a transcription factor family that induces transcription of many proinflammatory genes and may be an important mediator in carcinogenesis. We therefore tagged SNPs in more than 200 genes in the NF-?B pathway for a total of 2,282 SNPs (including rs17561) for genotype analysis of 15,604 cases of ovarian cancer in patients of European descent, including 6,179 of high-grade serous (HGS), 2,100 endometrioid, 1,591 mucinous, 1,034 clear cell, and 1,016 low-grade serous, including 23,235 control cases spanning 40 studies in the Ovarian Cancer Association Consortium. In this large population, we confirmed the association between rs17561 and clear cell ovarian cancer [OR, 0.84; 95% confidence interval (CI), 0.76-0.93; P = 0.00075], which remained intact even after excluding participants in the prior study (OR, 0.85; 95% CI, 0.75-0.95; P = 0.006). Considering a multiple-testing-corrected significance threshold of P < 2.5 × 10(-5), only one other variant, the TNFSF10 SNP rs6785617, was associated significantly with a risk of ovarian cancer (low malignant potential tumors OR, 0.85; 95% CI, 0.79-0.91; P = 0.00002). Our results extend the evidence that borderline tumors may have a distinct genetic etiology. Further investigation of how these SNPs might modify ovarian cancer associations with other inflammation-related risk factors is warranted. Cancer Res; 74(3); 852-61. ©2013 AACR.
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Risk of postmenopausal hormone therapy and patient history factors for the survival rate in women with endometrial carcinoma - Hein, Alexander; Schneider, Michael; Renner, Stefan; Fasching, Peter; Fießler, Cornelia; Titz, Susanna; Hartmann, Arndt; Beckmann, Matthias; Thiel, Falk C. (Archives of Gynecology and Obstetrics, 2019)
Purpose: Postmenopausal hormone therapy (HT) is known to affect the development of hormone-dependent endometrial carcinoma (type I EC). Several studies on breast and ovarian carcinoma have shown that HT influences the molecular profile and prognostic behavior of these tumors. This study aimed to investigate the influence of prior HT and other risk factors on the prognosis in a cohort of patients with invasive endometrial carcinoma (EC). Methods: Among 525 patients diagnosed with EC between 1987 and 2010, 426 postmenopausal patients were identified. Information regarding HT was available in 287 of these patients, 78 of whom had a history of HT and 209 of whom did not. Both overall survival (OS) and progression-free survival (PFS) were analyzed. In addition to OS and PFS, risk factors such as age at diagnosis, postmenopausal HT, body mass index (BMI), diabetes mellitus, tumor stage, EC type (I or II), and recurrences were analyzed. Results: Relative to HT alone, women with EC and a history of HT had a longer survival than those with no HT. However, the Cox proportional hazards model showed that it was not HT itself, but rather other characteristics in the HT group that were causally associated with longer survival. Conclusions: Age (the older, the worse) and tumor stage (the higher, the worse) were significant influences on overall survival. Patients with HT also had lower BMIs, less diabetes, more type I EC, and fewer recurrences in comparison with the non-HT group. With regard to the PFS, it made no difference whether the patient was receiving HT.
CRIS-Team Scopus Importer:2020-02-21
Keywords: Endometrial carcinoma; Estrogen; Hormone replacement therapy; Hormone therapy; Overall survival; Progesterone; Prognosis; Risk factors

Risk, Prediction and Prevention of Hereditary Breast Cancer - Large-Scale Genomic Studies in Times of Big and Smart Data - Wunderle, Marius; Olmes, Gregor; Nabieva, Naiba; Häberle, Lothar; Jud, Sebastian; Hein, Alexander; Rauh, Claudia; Hack, Carolin; Erber, Ramona; Ekici, Arif Bülent; Hoyer, Juliane; Vasileiou, Georgia; et al. (Geburtshilfe und Frauenheilkunde, 2018)
Over the last two decades genetic testing for mutations in BRCA1 and BRCA2 has become standard of care for women and men who are at familial risk for breast or ovarian cancer. Currently, genetic testing more often also includes so-called panel genes, which are assumed to be moderate-risk genes for breast cancer. Recently, new large-scale studies provided more information about the risk estimation of those genes. The utilization of information on panel genes with regard to their association with the individual breast cancer risk might become part of future clinical practice. Furthermore, large efforts have been made to understand the influence of common genetic variants with a low impact on breast cancer risk. For this purpose, almost 450 000 individuals have been genotyped for almost 500 000 genetic variants in the OncoArray project. Based on first results it can be assumed that - together with previously identified common variants - more than 170 breast cancer risk single nucleotide polymorphisms can explain up to 18% of familial breast cancer risk. The knowledge about genetic and non-genetic risk factors and its implementation in clinical practice could especially be of use for individualized prevention. This includes an individualized risk prediction as well as the individualized selection of screening methods regarding imaging and possible lifestyle interventions. The aim of this review is to summarize the most recent developments in this area and to provide an overview on breast cancer risk genes, risk prediction models and their utilization for the individual patient.
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Robot-assisted liver resection - Aselmann, H.; Moeller, T.; Kersebaum, J. -N.; Egberts, J. H.; Croner, R.; Brunner, Michaela; Grützmann, Robert; Becker, T. (Chirurg, 2017)
Robotic liver resection can overcome some of the limitations of laparoscopic liver surgery; therefore, it is a promising tool to increase the proportion of minimally invasive liver resections. The present article gives an overview of the current literature. Furthermore, the results of a nationwide survey on robotic liver surgery among hospitals in Germany with a DaVinci system used in general visceral surgery and the perioperative results of two German robotic centers are presented.
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Robotic-Assisted Liver Surgery - Croner, R.; Perrakis, Aristotelis; Grützmann, Robert; Hohenberger, Werner; Brunner, Michaela (Zentralblatt für Chirurgie, 2016)
The advantages of minimally invasive liver resections for selected patients are evident. Robots provide new innovations that will influence minimally invasive liver surgery in the future. This article presents our initial experience with this technology in our patient population. Material und Methods: In 14 patients with benign or malignant liver tumours, robotic-assisted liver surgery was performed. Selection criteria were compensated liver function and resection of <= 3 liver segments. Chronic liver disease or previous abdominal surgery were no exclusion criteria.Malignant liver tumours were removed in 10 patients (71 %) and benign symptomatic liver tumors in 3 patients (21 %), respectively, with histopathologically negative margins (R0). One patient suffering from HCC underwent intraoperative ablation. In one case (7 %) conversion was necessary. Mean operation time was 296 min (120-458 min); mean estimated blood loss was 319 ± 298 ml. The mean hospital stay of the patients was 8 days (3-17 days). Three patients (21 %) suffered from postoperative complications, which were manageable by conservative treatment (Clavien-Dindo I) in 2 cases (14 %). One patient (7 %) needed endoscopic treatment for postoperative bile leak (Clavien-Dindo III a). No patient died intra- or perioperatively.Robotic-assisted liver surgery is a safe procedure, which provides patients with all benefits of minimally invasive surgery. This highly advanced technology requires surgeons to strive for an increasing level of specialisation, in addition to being well-trained in liver surgery. Hence, a clear definition of the procedures and standardised teaching programs are necessary.
EVALuna2:15228

Robotic liver surgery for minor hepatic resections: a comparison with laparoscopic and open standard procedures - Croner, Roland S.; Perrakis, Aristotelis; Hohenberger, Werner; Brunner, Michaela (Langenbecks Archives of Surgery, 2016)
Minimally invasive liver surgery is increasing worldwide. The benefit of the robot in this scenario is currently controversially discussed. We compared our robotic cases vs. laparoscopic and open minor hepatic resections and share the experience.From 2011 to 2015, ten patients underwent robotic and 19 patients underwent laparoscopic minor liver resections in the Department of Surgery, University Hospital Erlangen. These patients were compared to a case-matched control group of 53 patients. The perioperative prospectively collected data were analyzed retrospectively.Blood loss was significantly decreased in the robotic (306 ml) and laparoscopic (356 ml) vs. the open (903 ml) surgery group (p = 0.001). Mean tumor size was 4.1-4.8 cm in all groups (p = 0.571). Negative surgical margins were present in 94 % of the open and 100 % of the laparoscopic and robotic group (p = 0.882). Time for surgery was enlarged for robotic (321 min) vs. laparoscopic (242 min) and open (186 min) surgery (p = 0.001). Postoperative hospitalization was decreased after robotic (7 days) and laparoscopic (8 days) vs. open (10 days) surgery (p = 0.004). Total morbidity was 17 % for open, 16 % for laparoscopic, and 1 % for robotic cases (p = 0.345). Postoperative pain medication and elevation of liver enzymes were remarkably lower after minimally invasive vs. open procedures.Minimally invasive liver surgery can be performed safely for minor hepatic resections and should be considered whenever possible. Minor liver resections can be performed by standard laparoscopy equivalent to robotic procedures. Nevertheless, the robot adds a technical upgrade which may have benefits for challenging cases and major liver surgery.
EVALuna2:15231

Role of adipokines in embryo implantation - Jafari-Gharabaghlou, Davoud; Vaghari-Tabari, Mostafa; Oghbaei, Hajar; Lotz, Laura; Zarezadeh, Reza; Rezaei, Yeganeh Rastgar; Ranjkesh, Mahnaz; Nouri, Mohammad; Fattahi, Amir; Nikanfar, Saba; Dittrich, Ralf (Endocrine Connections, 2021)
Embryo implantation is a complex process in which multiple molecules acting together under strict regulation. Studies showed the production of various adipokines and their receptors in the embryo and uterus, where they can influence the maternal-fetal transmission of metabolites and embryo implantation. Therefore, these cytokines have opened a novel area of study in the field of embryo–maternal crosstalk during early pregnancy. In this respect, the involvement of adipokines has been widely reported in the regulation of both physiological and pathological aspects of the implantation process. However, the information about the role of some recently identified adipokines is limited. This review aims to highlight the role of various adipokines in embryo–maternal interactions, endometrial receptivity, and embryo implantation, as well as the underlying molecular mechanisms.
CRIS-Team Scopus Importer:2021-12-17
Keywords: Adipokine; Embryo implantation; Endometrium; Pregnancy; Trophoblast

Role of adipokines in the ovarian function: Oogenesis and steroidogenesis - Nikanfar, Saba; Oghbaei, Hajar; Rastgar Rezaei, Yeganeh; Zarezadeh, Reza; Jafari-gharabaghlou, Davoud; Nejabati, Hamid Reza; Bahrami, Zahra; Bleisinger, Nathalie; Samadi, Naser; Fattahi, Amir; Nouri, Mohammad; Dittrich, Ralf (Journal of Steroid Biochemistry and Molecular Biology, 2021)
Adipokines are mainly produced by adipose tissue; however, their expression has been reported in other organs including female reproductive tissues. Therefore, adipokines have opened new avenues of research in female fertility. In this regard, studies reported different roles for certain adipokines in ovarian function, although the role of other recently identified adipokines is still controversial. It seems that adipokines are essential for normal ovarian function and their abnormal levels could be associated with ovarian-related disorders. The objective of this study is to review the available information regarding the role of adipokines in ovarian functions including follicular development, oogenesis and steroidogenesis and also their involvement in ovary-related disorders.
CRIS-Team Scopus Importer:2021-03-12
Keywords: Adiponectin; Follicle; Granulosa cells; Leptin; Oocyte

Role of Pelvic Lymph Node Resection in Vulvar Squamous Cell Cancer: A Subset Analysis of the AGO-CaRE-1 Study - Woelber, Linn; Bommert, Mareike; Harter, Philipp; Prieske, Katharina; zu Eulenburg, Christine; Jueckstock, Julia; Hilpert, Felix; de Gregorio, Nikolaus; Iborra, Severine; Sehouli, Jalid; Ignatov, Atanas; Hillemanns, Peter; et al. (Annals of Surgical Oncology, 2021)
Background: As the population at risk for pelvic nodal involvement remains poorly described, the role of pelvic lymphadenectomy (LAE) in vulvar squamous cell cancer (VSCC) has been a matter of discussion for decades. Methods: In the AGO-CaRE-1 study, 1618 patients with International Federation of Gynecology and Obstetrics (FIGO) stage IB or higher primary VSCC treated at 29 centers in Germany between 1998 and 2008 were documented. In this analysis, only patients with pelvic LAE (n = 70) were analyzed with regard to prognosis and correlation between inguinal and pelvic lymph node involvement. Results: The majority of patients had T1b/T2 tumors (n = 47; 67.1%), with a median diameter of 40 mm (2–240 mm); 54/70 patients (77.1%) who received pelvic LAE had positive groin nodes. For 42 of these 54 patients, the number of affected groin nodes had been documented as a median of 3; 14/42 (33.3%) of these patients had histologically confirmed pelvic nodal metastases (median number of affected pelvic nodes 3 [1–12]). In these 14 patients, the median number of affected groin nodes was 7 (1–30), with a groin metastases median maximum diameter of 42.5 mm (12–50). Receiver operating characteristic analysis showed an area under the curve of 0.85, with 83.3% sensitivity and 92.6% specificity for the prediction of pelvic involvement in cases of six or more positive groin nodes. No cases of pelvic nodal involvement without groin metastases were observed. Prognosis in cases of pelvic metastasis was poor, with a median progression-free survival of only 12.5 months. Conclusion: For the majority of node-positive patients with VSCC, pelvic nodal staging appears unnecessary since a relevant risk for pelvic nodal involvement only seems to be present in highly node-positive disease.
CRIS-Team Scopus Importer:2021-04-02

rs2735383, located at a microRNA binding site in the 3'UTR of NBS1, is not associated with breast cancer risk - Liu, Jingjing; Loncar, Ivona; Collee, J. Margriet; Bolla, Manjeet K.; Dennis, Joe; Michailidou, Kyriaki; Wang, Qin; Andrulis, Irene L.; Barile, Monica; Beckmann, Matthias; Behrens, Sabine; Benitez, Javier; et al. (Scientific Reports, 2016)
NBS1, also known as NBN, plays an important role in maintaining genomic stability. Interestingly, rs2735383 G > C, located in a microRNA binding site in the 3'-untranslated region (UTR) of NBS1, was shown to be associated with increased susceptibility to lung and colorectal cancer. However, the relation between rs2735383 and susceptibility to breast cancer is not yet clear. Therefore, we genotyped rs2735383 in 1,170 familial non-BRCA1/2 breast cancer cases and 1,077 controls using PCR-based restriction fragment length polymorphism (RFLP-PCR) analysis, but found no association between rs2735383CC and breast cancer risk (OR = 1.214, 95% CI = 0.936-1.574, P = 0.144). Because we could not exclude a small effect size due to a limited sample size, we further analyzed imputed rs2735383 genotypes (r2 > 0.999) of 47,640 breast cancer cases and 46,656 controls from the Breast Cancer Association Consortium (BCAC). However, rs2735383CC was not associated with overall breast cancer risk in European (OR = 1.014, 95% CI = 0.969-1.060, P = 0.556) nor in Asian women (OR = 0.998, 95% CI = 0.905-1.100, P = 0.961). Subgroup analyses by age, age at menarche, age at menopause, menopausal status, number of pregnancies, breast feeding, family history and receptor status also did not reveal a significant association. This study therefore does not support the involvement of the genotype at NBS1 rs2735383 in breast cancer susceptibility.
EVALuna2:33244

rs495139 in the TYMS-ENOSF1 Region and Risk of Ovarian Carcinoma of Mucinous Histology - Kelemen, Linda E.; Earp, Madalene; Fridley, Brooke L.; Chenevix-Trench, Georgia; Fasching, Peter; Beckmann, Matthias; Ekici, Arif Bülent; Hein, Alexander; Lambrechts, Diether; Lambrechts, Sandrina; Van Nieuwenhuysen, Els; Vergote, Ignace; et al. (International Journal of Molecular Sciences, 2018)
Thymidylate synthase (TYMS) is a crucial enzyme for DNA synthesis. TYMS expression is regulated by its antisense mRNA, ENOSF1. Disrupted regulation may promote uncontrolled DNA synthesis and tumor growth. We sought to replicate our previously reported association between rs495139 in the TYMS-ENOSF1 3' gene region and increased risk of mucinous ovarian carcinoma (MOC) in an independent sample. Genotypes from 24,351 controls to 15,000 women with invasive OC, including 665 MOC, were available. We estimated per-allele odds ratios (OR) and 95% confidence intervals (CI) using unconditional logistic regression, and meta-analysis when combining these data with our previous report. The association between rs495139 and MOC was not significant in the independent sample (OR = 1.09; 95% CI = 0.97⁻1.22; p = 0.15; N = 665 cases). Meta-analysis suggested a weak association (OR = 1.13; 95% CI = 1.03⁻1.24; p = 0.01; N = 1019 cases). No significant association with risk of other OC histologic types was observed (p = 0.05 for tumor heterogeneity). In expression quantitative trait locus (eQTL) analysis, the rs495139 allele was positively associated with ENOSF1 mRNA expression in normal tissues of the gastrointestinal system, particularly esophageal mucosa (r = 0.51, p = 1.7 × 10-28), and nonsignificantly in five MOC tumors. The association results, along with inconclusive tumor eQTL findings, suggest that a true effect of rs495139 might be small.
EVALuna2:35118

S1 Guideline: Impairment of gonadal function after Cancer in Childhood and Adolescence - Borgmann-Staudt, Anja; Jantke, Andreas; Hinz, Stefan; Beckmann, Matthias; Dittrich, Ralf; Lotz, Laura; Balcerek, Magdalena (Klinische Pädiatrie, 2023)
A possible negative consequence of cancer treatment is the fertility impairment of young cancer survivors. However, most former patients express the wish to have biological children. Fertility-preserving measures are available and are - under certain circumstances - financed by health insurance. Separate information at the time of diagnosis and during follow-up care should be adapted to the individual risk and enable those affected to make a self-determined decision about cryopreservation of germ cells or germ cell tissue. Hyopgonadotropic hypogonadism can be treated by the pulsatile administration of gonadotropins. Affected individuals can be reassured. A health restriction of the offspring due to the cancer treatment is not to be expected, even after artificial insemination.
CRIS-Team Scopus Importer:2023-09-22
Keywords: childhood cancer; fertility impairment treatment; offspring health; patient education; self-determined decision

S3 guidelines on diagnostics and treatment of cervical cancer: Demands on pathology - Horn, L. -C.; Beckmann, Matthias; Follmann, M.; Koch, Matthias; Mallmann, P.; Marnitz, S.; Schmidt, D. (Pathologe, 2015)
Between 2011 and the end of 2014 the former consensus S2k guidelines for the diagnostics and treatment of cervical cancer were updated and upgraded to S3 level, methodologically based on the regulations of the German Cancer Society (DKG). The present article summarizes the relevant aspects for the sectioning, histopathological workup, diagnostics and reporting for the pathology of invasive cancer of the uterine cervix. The recommendations are based on the most recent World Health Organization (WHO) and TNM classification systems and consider the needs of the clinician for appropriate surgical and radiotherapeutic treatment of patients. Detailed processing rules of colposcopy-guided diagnostic biopsies, conization and trachelectomy as well as for radical hysterectomy specimens and lymph node resection (including sentinel lymph node resection) are given. In the guidelines deep stromal invasion in macroinvasive cervical cancer is defined for the first time as tumor infiltration of > 66% of the cervical stromal wall. Furthermore, morphological prognostic factors for microinvasive and macroinvasive cervical cancer are summarized.
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S3 guidelines on the diagnosis and treatment of carcinoma of the endometrium : Requirements for pathology - Horn, L. -C.; Emons, G.; Aretz, Stefan; Bock, N.; Follmann, Markus; Lax, Sigurd F.; Nothacker, M.; Steiner, E.; Mayr, D.; Alt-Epping, Bernd; Aretz, Stefan; Bauerschmitz, Gerd; et al. (Pathologe, 2019)
The present article summarises the relevant aspects of the S3 guidelines on endometrioid carcinomas. The recommendations include the processing rules of fractional currettings as well as for hysterectomy specimens and lymph node resections (including sentinel lymph nodes). Besides practical aspects, the guidelines consider the needs of the clinicians for appropriate surgical and radiotherapeutic treatment of the patients. Carcinosarcomas are assigned to the endometrial carcinoma as a special variant. For the first time, an algorithmic approach for evaluation of the tumour tissue for Lynch syndrome is given. Prognostic factors based on morphologic findings are summarised.
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Sacral nerve stimulation for faecal incontinence in patients with sacral malformation - Brunner, Michaela; Cui, Z.; Matzel, Klaus (International Journal of Colorectal Disease, 2017)
Sacral nerve stimulation (SNS) is a common and effective treatment for faecal incontinence (FI), but accessibility of the sacral nerves is mandatory. In some cases, electrode placement fails for unknown reasons. A frequent cause could be sacral malformations, which have a high incidence (up to 24.1%) and can be unsuspected.We report two patients with FI consequent to congenital anorectal malformation and associated sacral malformation. Despite partial sacral agenesis, SNS was feasible in both. They benefitted greatly from SNS, with an improved ability to postpone the urge up to at least 15 min, reduced incontinence episodes (at least 50%), and significantly better quality of life.SNS may be feasible in patients with FI, even in the presence of sacral malformation. However, clinicians should be aware of the attendant technical difficulties. Preoperative imaging, preferably with MRI of the sacrum, is advisable. If the sacral spinal nerves are inaccessible technically, pudendal nerve stimulation could be considered, if anatomy permits.
EVALuna2:15239

Safety and immunogenicity of neoadjuvant treatment using WT1-immunotherapeutic in combination with standard therapy in patients with WT1-positive Stage II/III breast cancer: a randomized Phase I study - Higgins, M.; Curigliano, Giuseppe; Dieras, V.; Kuemmel, S.; Kunz, G.; Fasching, Peter; Campone, M.; Bachelot, T.; Krivorotko, P.; Chan, S.; Ferro, A.; Schwartzberg, L.; et al. (Breast Cancer Research and Treatment, 2017)
PURPOSE: This Phase I, multicenter, randomized study (ClinicalTrials.gov NCT01220128) evaluated the safety and immunogenicity of recombinant Wilms' tumor 1 (WT1) protein combined with the immunostimulant AS15 (WT1-immunotherapeutic) as neoadjuvant therapy administered concurrently with standard treatments in WT1-positive breast cancer patients. METHODS: Patients were treated in 4 cohorts according to neoadjuvant treatment (A: post-menopausal, hormone receptor [HR]-positive patients receiving aromatase inhibitors; B: patients receiving chemotherapy; C: HER2-overexpressing patients on trastuzumab-chemotherapy combination; D: HR-positive/HER2-negative patients on chemotherapy). Patients (cohorts A-C) were randomized (2:1) to receive 6 or 8 doses of WT1-immunotherapeutic or placebo together with standard neoadjuvant treatment in a double-blind manner; cohort D patients received WT1-immunotherapeutic in an open manner. Safety was assessed throughout the study. WT1-specific antibodies were assessed pre- and post-vaccination. RESULTS: Sixty-two patients were randomized; 60 received ≥ one dose of WT1-immunotherapeutic. Two severe toxicities were reported: diarrhea (cohort C; also reported as a grade 3 serious adverse event) and decreased left ventricular ejection fraction (cohort B; also reported as a grade 2 adverse event). Post-dose 4 of WT1-immunotherapeutic, 10/10 patients from cohort A, 0/8 patients from cohort B, 6/11 patients from cohort C, and 2/3 patients from cohort D were humoral responders. The sponsor elected to close the trial prematurely. CONCLUSIONS: Concurrent administration of WT1-immunotherapeutic and standard neoadjuvant therapy was well tolerated and induced WT1-specific antibodies in patients receiving neoadjuvant aromatase inhibitors. In patients on neoadjuvant chemotherapy or trastuzumab-chemotherapy combination, the humoral response was impaired or blunted, likely due to either co-administration of corticosteroids and/or the chemotherapies themselves.
EVALuna2:36200

Safety interim analysis (SIA) of the phase III postneoadjuvant SASCIA study evaluating sacituzumab govitecan (SG) in patients (pts) with primary HER2-negative breast cancer (BC) at high relapse risk after neoadjuvant chemotherapy (NACT) - Marme, Frederik; Hanusch, Claus; Furlanetto, Jenny; Morris, Patrick; Link, Theresa; Denkert, Carsten; Fasching, Peter; Jackisch, Christian; Antolin, Silvia; Solbach, Christine; Aftimos, Philippe; Huober, Jens; et al. (ONCOLOGY RESEARCH AND TREATMENT, 2022)
CRIS-Team WoS Importer:2022-12-16

Safety interim analysis (SIA) of the phase III postneoadjuvant SASCIA study evaluating sacituzumab govitecan (SG) in patients with primary HER2-negative breast cancer (BC) at high relapse risk after neoadjuvant treatment - Marme, F.; Hanusch, C.; Furlanetto, J.; Morris, P.; Link, T.; Denkert, C.; Fasching, Peter; Jackisch, C.; Antolin, S.; Solbach, C.; Aftimos, P.; Huober, J.; et al. (ANNALS OF ONCOLOGY, 2022)
CRIS-Team WoS Importer:2022-06-03

Salivary and hair cortisol as biomarkers of emotional and behavioral symptoms in 6–9 year old children - Golub, Yulia; Kuitunen-Paul, Sören; Panaseth, Kerstin; Stonawski, Valeska; Frey, Stefan; Steigleder, Ruth; Grimm, Jennifer; Goecke, Tamme W.; Fasching, Peter; Beckmann, Matthias; Kornhuber, Johannes; Kratz, Oliver; et al. (Physiology & behavior, 2019)
The aim of the present work is to investigate the association of salivary and cumulative cortisol levels with emotional and behavioral symptoms in a Franconian Cognition and Emotion Studies (FRANCES) general population cohort of 158 6- to 9 year old children. Salivary cortisol values were measured by one-day diurnal cortisol profile, whereas cumulative cortisol was estimated via one-month hair cortisol concentrations (rHCC). Nearly all significant associations of clinical symptoms with child cortisol indices were age dependent: We report emotional symptoms being associated with lower rHCC in younger children (6.06–7.54 years). In older children (7.55–9.41 years) behavioral problems were further associated with higher rHCC and lower salivary cortisol awakening responses. In summary, child clinical symptoms were stronger associated with markers of hair cortisol compared to salivary cortisol. To picture developmental mechanisms, we suggest longitudinal designs for cortisol measures of stress systems in children and adolescents.
CRIS-Team Scopus Importer:2019-07-02
Keywords: Behavioral symptoms; Emotional symptoms; FRANCES; Hair cortisol; HPA axis; Salivary cortisol

Saliva samples as a source of DNA for high throughput genotyping: an acceptable and sufficient means in improvement of risk estimation throughout mammographic diagnostics - Poehls, U. G.; Hack, Caroline; Ekici, Arif Bülent; Beckmann, Matthias; Fasching, Peter; Rübner, Matthias; Hübner, Hanna (European Journal of Medical Research, 2018)
BACKGROUND: Breast cancer screening programs seem to be an insufficient tool for women at high genetic risk for breast cancer. These women are not adequately monitored yet. Genetic testing may improve clearly the quality of breast cancer prevention programs. At present, blood samples are favored for obtaining high-quality DNA; however, DNA can also be obtained by collecting saliva. The aim of this study was, on the one hand, to determine whether saliva sampling is a practicable means to obtain sufficient quantity and quality of DNA and, on the other hand, whether it is accepted by patients throughout mammographic diagnostics. METHODS: 67 consecutive women with diagnostic need for mammography with or without a family history for breast cancer were asked for their basic willingness to undergo a genetic testing by saliva sample in addition to standard diagnostics. Saliva samples were analyzed in terms of DNA quantity and quality. RESULTS: 64 (95.6%) women agreed to provide a saliva sample; 3 of them denied participation. And even 63 out of 64 (98.4%) were interested in their specific results. 45 out of 64 samples contained a DNA concentration above 50 ng/µl, 12 samples were between 25 and 50 ng/µl and only 7 of them were under 25 ng/µl with the standard extraction procedure. CONCLUSION: A high number of patients seem to accept salvia samples as a risk assessment tool in breast diagnostics and are interested in their specific risk situation. At the same time, it could be demonstrated that it is an effective way to provide high-quality DNA for breast cancer gene analysis. However, it remains to be shown whether it would be possible to integrate it with the same acceptance in a nationwide breast cancer screening program.
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Sarcoma of the Uterus. Guideline of the DGGG and OEGGG (S2k Level, AWMF Register Number 015/074, February 2019) - Denschlag, Dominik; Ackermann, Sven; Battista, Marco Johannes; Cremer, Wolfgang; Egerer, Gerlinde; Follmann, Markus; Haas, Heidemarie; Harter, Philipp; Hettmer, Simone; Horn, Lars Christian; Juhasz-Boess, Ingolf; Kast, Karin; et al. (Geburtshilfe und Frauenheilkunde, 2019)
Aims This is an official guideline published and coordinated by the German Society of Gynecology and Obstetrics (DGGG) and the Austrian Society of Gynecology and Obstetrics (OEGGG). Because of their rarity and heterogeneous histopathology, uterine sarcomas are challenging in terms of how they should be managed clinically, and treatment requires a multidisciplinary approach. To our knowledge, there are currently no binding evidence-based recommendations for the appropriate management of this heterogeneous group of tumors. Methods This S2k guideline was first published in 2015. The update published here is the result of the consensus of a representative interdisciplinary group of experts who carried out a systematic search of the literature on uterine sarcomas in the context of the guidelines program of the DGGG, OEGGG and SGGG. Members of the participating professional societies achieved a formal consensus after a moderated structured consensus process. Recommendations The consensus-based recommendations and statements include the epidemiology, classification, staging, symptoms, general diagnostic work-up and general pathology of uterine sarcomas as well as the genetic predisposition to develop uterine sarcomas. Also included are statements on the management of leiomyosarcomas, (low and high-grade) endometrial stromal sarcomas and undifferentiated uterine sarcomas and adenosarcomas. Finally, the guideline considers the follow-up and morcellation of uterine sarcomas and the information provided to patients.
CRIS-Team Scopus Importer:2019-11-05
Keywords: adenosarcoma; endometrial stromal sarcoma; leiomyosarcoma; morcellation; uterine sarcoma

Sarcoma of the UterusGuideline of the DGGG, OEGGG and SGGG (S2k-Level, AWMF Registry No. 015/074, April 2021) - Denschlag, Dominik; Ackermann, Sven; Battista, Marco Johannes; Cremer, Wolfgang; Egerer, Gerlinde; Fehr, Matthias; Follmann, Markus; Haase, Heidemarie; Harter, Philipp; Hettmer, Simone; Horn, Lars Christian; Juhasz-Boess, Ingolf; et al. (Geburtshilfe und Frauenheilkunde, 2022)
Purpose This is an official guideline, published and coordinated by the Germany Society for Gynecology and Obstetrics (Deutsche Gesellschaft für Gynäkologie und Geburtshilfe, DGGG). Because of their rarity and heterogeneous histopathology, uterine sarcomas are challenging in terms of their clinical management and therefore require a multidisciplinary approach. To our knowledge, there are currently no binding evidence-based recommendations for the appropriate management of this heterogeneous group of tumors. Methods This S2k guideline was first published in 2015. The update published here is once again the result of the consensus of a representative interdisciplinary committee of experts who were commissioned by the Guidelines Committee of the DGGG to carry out a systematic search of the literature on uterine sarcomas. Members of the participating professional societies achieved a formal consensus after a structured consensus process. Recommendations 1.1 Epidemiology, classification, staging of uterine sarcomas. 1.2 Symptoms, general diagnostic workup, general pathology or genetic predisposition to uterine sarcomas. 2. Management of leiomyosarcomas. 3. Management of low-grade endometrial stromal sarcomas. 4. Management of high-grade endometrial stromal sarcoma and undifferentiated uterine sarcomas. 5. Management of adenosarcomas. 6. Rhabdomyosarcomas of the uterus in children and adolescents. 7. Follow-up of uterine sarcomas. 8. Management of morcellated uterine sarcomas. 9. Information provided to patients.
CRIS-Team Scopus Importer:2022-12-16
Keywords: adenosarcoma; endometrial stromal sarcoma; guideline; leiomyosarcoma; morcellation; uterine sarcoma

Sarcoma of the Uterus. Guideline of the DGGG (S2k-Level, AWMF Registry No. 015/074, August 2015) - Denschlag, D.; Thiel, F. C.; Ackermann, S.; Harter, P.; Juhasz-Boess, I.; Mallmann, P.; Strauss, H. -G.; Ullrich, U.; Horn, L. -C.; Schmidt, D.; Vordermark, D.; Vogl, T.; et al. (Geburtshilfe und Frauenheilkunde, 2015)
Purpose: Official guideline published and coordinated by the German Society of Gynecology and Obstetrics (DGGG). Due to their rarity and their heterogeneous histopathology uterine sarcomas remain challenging tumors to manage and need a multidisciplinary approach. To our knowledge so far there is no evidence-based guideline on the appropiate management of these heterogeneous tumors. Methods: This S2k-guideline is the work of an representative committee of experts from a variety of different professions who were commissioned by the DGGG to carry out a systematic literature review of uterine sarcoma. Members of the participating scientific societies developed a structured consensus in a formal procedure. Recommendations: 1. The incidence and histopathologic classification of uterine sarcoma. 2. The clinical manifestations, diagnosis and staging of uterine sarcoma. 3. The management of leiomyosarcoma. 4. The management of endometrial stromal sarcoma and undifferentiated uterine sarcoma. 5. The management of adenosarcoma as well as carcinosarcomas. 6. The management of morcellated uterine sarcoma.
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SARS-CoV-2 Infection in Pregnancy - a Review of the Current Literature and Possible Impact on Maternal and Neonatal Outcome - Stumpfe, Florian; Titzmann, Adriana; Schneider, Michael; Stelzl, Patrick; Kehl, Sven; Fasching, Peter; Beckmann, Matthias; Enßer, Armin (Geburtshilfe und Frauenheilkunde, 2020)
In December 2019, cases of pneumonia of unknown cause first started to appear in Wuhan in China; subsequently, a new coronavirus was soon identified as the cause of the illness, now known as Coronavirus Disease 2019 (COVID-19). Since then, infections have been confirmed worldwide in numerous countries, with the number of cases steadily rising. The aim of the present review is to provide an overview of the new severe acute respiratory syndrome (SARS) coronavirus 2 (SARS-CoV-2) and, in particular, to deduce from it potential risks and complications for pregnant patients. For this purpose, the available literature on cases of infection in pregnancy during the SARS epidemic of 2002/2003, the MERS (Middle East respiratory syndrome) epidemic ongoing since 2012, as well as recent publications on cases infected with SARS-CoV-2 in pregnancy are reviewed and reported. Based on the literature available at the moment, it can be assumed that the clinical course of COVID-19 disease may be complicated by pregnancy which could be associated with a higher mortality rate. It may also be assumed at the moment that transmission from mother to child in utero is unlikely. Breastfeeding is possible once infection has been excluded or the disease declared cured.
CRIS-Team Scopus Importer:2020-05-19
Keywords: 2019-nCoV; coronavirus; COVID-19; pregnancy; SARS-CoV-2

Sebaceous breast carcinoma: report of a rare histological special subtype - Wachter, David; Rauh, C.; Wenkel, Evelyn; Fasching, Peter; Beckmann, Matthias; Hartmann, Arndt (Pathologe, 2014)
We report on a case of sebaceous carcinoma of the breast as a rare histological special subtype of breast cancer. Because these tumors are uncommon, differential diagnostic considerations and the exclusion of Muir-Torre syndrome are emphasized. Finally possible mechanisms of development and therapeutic strategies for this carcinoma are discussed.
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Selective expression of sense and antisense transcripts of the sushi-ichi-related retrotransposon - derived family during mouse placentogenesis - Henke, Christine; Strissel, Pamela; Schubert, Maria-Theresa; Mitchell, Megan; Stolt, Claus; Faschingbauer, Florian; Beckmann, Matthias; Strick, Reiner (Retrovirology, 2015)
LTR-retrotransposons became functional neogenes through evolution by acquiring promoter sequences, regulatory elements and sequence modification. Mammalian retrotransposon transcripts (Mart1-9), also called sushi-ichi-related retrotransposon-homolog (SIRH) genes, are a class of Ty3/gypsy LTR-retroelements showing moderate homology to the sushi-ichi LTR-retrotransposon in pufferfish. Rtl1/Mart1 and Peg10/Mart2 expression in mouse placenta and demonstration of their functional roles during placental development exemplifies their importance in cellular processes. In this study, we analyzed all eleven mouse Mart genes from the blastocyst stage and throughout placentogenesis in order to gain information about their expression and regulation.Quantitative PCR, in situ hybridization (ISH) and immunoblotting showed various expression patterns of the 11 mouse Mart genes through different placental stages. Zcchc5/Mart3, Zcchc16/ Mart4 and Rgag1/Mart9 expression was undetectable. Rtl1/Mart1, Peg10/Mart2, Rgag4/Mart5 - Cxx1a,b,c/Mart8b,c,a gene expression was very low at the blastocyst stage. Later placental stages showed an increase of expression for Rtl1/Mart1, Rgag4/Mart5 - Cxx1a,b,c/Mart8b,c,a, the latter up to 1,489 molecules/ng cDNA at E9.5. From our recently published findings Peg10/Mart2 was the most highly expressed Mart gene. ISH demonstrated sense and antisense transcript co-localization of Rgag4/Mart5 to Cxx1a,b,c/Mart8b,c,a in trophoblast subtypes at the junctional zone, with an accumulation of antisense transcripts in the nuclei. To validate these results, we developed a TAG-aided sense/antisense transcript detection (TASA-TD) method, which verified sense and antisense transcripts for Rtl1/Mart1, Rgag4/Mart5 - Cxx1a,b,c/Mart8b,c,a. Except for Rtl1/Mart1 and Cxx1a,b/Mart8b,c all other Mart genes showed a reduced amount of antisense transcripts. Northern blot and 5' and 3' RACE confirmed both sense and antisense transcripts for Ldoc1/Mart7 and Cxx1a,b,c/Mart8b,c,a. Immunoblotting demonstrated a single protein throughout all placental stages for Ldoc1/Mart7, but for Cxx1a,b,c/Mart8b,c,a a switch occurred from a 57 kDa protein at E10.5 and E14.5 to a 25 kDa protein at E16.5 and E18.5.RNA and protein detection of mouse Mart genes support neo-functionalization of retrotransposons in mammalian genomes. Undetectable expression of Zcchc5/Mart3, Zcchc16/Mart4 and Rgag1/Mart9 indicate no role during mouse placentogenesis. Rgag4/Mart5 to Cxx1a,b,c/Mart8b,c,a gene expression support a role for differentiation from the ectoplacental cone. Mart antisense transcripts and protein alterations predict unique and complex molecular regulation in a time directed manner throughout mouse placentogenesis.
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Selective isolation and characterization of primary cells from normal breast and tumors reveal plasticity of adipose derived stem cells - Weigand, Annika; Boos, Anja; Tasbihi, Kereshmeh; Beier, Justus; Dalton, Paul D.; Schrauder, Michael; Horch, Raymund E.; Beckmann, Matthias; Strissel, Pamela; Strick, Reiner (Breast Cancer Research, 2016)
There is a need to establish more cell lines from breast tumors in contrast to immortalized cell lines from metastatic effusions in order to represent the primary tumor and not principally metastatic biology of breast cancer. This investigation describes the simultaneous isolation, characterization, growth and function of primary mammary epithelial cells (MEC), mesenchymal cells (MES) and adipose derived stem cells (ADSC) from four normal breasts, one inflammatory and one triple-negative ductal breast tumors.A total of 17 cell lines were established and gene expression was analyzed for MEC and MES (n = 42) and ADSC (n = 48) and MUC1, pan-KRT, CD90 and GATA-3 by immunofluorescence. DNA fingerprinting to track cell line identity was performed between original primary tissues and isolates. Functional studies included ADSC differentiation, tumor MES and MEC invasion co-cultured with ADSC-conditioned media (CM) and MES adhesion and growth on 3D-printed scaffolds.Comparative analysis showed higher gene expression of EPCAM, CD49f, CDH1 and KRTs for normal MEC lines; MES lines e.g. Vimentin, CD10, ACTA2 and MMP9; and ADSC lines e.g. CD105, CD90, CDH2 and CDH11. Compared to the mean of all four normal breast cell lines, both breast tumor cell lines demonstrated significantly lower ADSC marker gene expression, but higher expression of mesenchymal and invasion gene markers like SNAI1 and MMP2. When compared with four normal ADSC differentiated lineages, both tumor ADSC showed impaired osteogenic and chondrogenic but enhanced adipogenic differentiation and endothelial-like structures, possibly due to high PDGFRB and CD34. Addressing a functional role for overproduction of adipocytes, we initiated 3D-invasion studies including different cell types from the same patient. CM from ADSC differentiating into adipocytes induced tumor MEC 3D-invasion via EMT and amoeboid phenotypes. Normal MES breast cells adhered and proliferated on 3D-printed scaffolds containing 20 fibers, but not on 2.5D-printed scaffolds with single fiber layers, important for tissue engineering.Expression analyses confirmed successful simultaneous cell isolations of three different phenotypes from normal and tumor primary breast tissues. Our cell culture studies support that breast-tumor environment differentially regulates tumor ADSC plasticity as well as cell invasion and demonstrates applications for regenerative medicine.
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Self-reported Improvement in Side Effects and Quality of Life With Integrative Medicine in Breast Cancer Patients - Hack, Carolin; Hackl, Janina; Huettner, Nina B. M.; Langemann, Hanna; Schwitulla, Judith; Dietzel-Drentwett, Svenja; Fasching, Peter; Beckmann, Matthias; Theuser, Anna-Katharin (Integrative Cancer Therapies, 2018)
PURPOSE: Although the demand from patients for integrative medicine is increasing, complementary medicine services are still quite heterogeneous and have not been incorporated into clinical routine. The aim of this study was to systematically evaluate improvements in side effects and quality of life associated with a hospital-based integrative medicine program in the modern breast cancer patient care setting. METHODS: In a cross-sectional study, integrative health counseling and treatment were evaluated in women with breast cancer. Over a 15-month period, data for 75 patients from an integrative medicine consultancy service with standardized operating procedures were collected at the University Breast Center for Franconia. At baseline, the patients answered a questionnaire on their medical history, symptoms, and the treatment goals they were hoping to achieve with integrative medicine. In the follow-up, patient-reported outcomes related to side effects of conventional cancer treatment and patients' quality of life were analyzed. RESULTS: Among 60 patients with the therapy goal of reducing the side effects of conventional treatment, 46 (76.7%) were successful. Among 57 patients hoping to improve disease-related quality of life, 46 (82%) reported success. Whereas patients with metastatic disease achieved a reduction in the side effects of conventional therapy, quality-of-life improvements were predominantly achieved by patients with a good treatment prognosis. CONCLUSIONS: Breast cancer patients benefit from the counseling and treatment provided with integrative medicine in all phases of tumor disease. Integrative treatment services should be included as part of patient care in clinical routine work to offer patients the maximum quality of care and safety with complementary therapies.
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Semi-automated De-identification of German Content Sensitive Reports for Big Data Analytics - Seuß, Hannes; Dankerl, Peter; Ihle, Matthias; Grandjean, Andrea; Hammon, Rebecca; Kaestle, Nicola; Fasching, Peter; Maier, Christian; Christoph, Jan; Sedlmayr, Martin; Uder, Michael; Hammon, Matthias; et al. (Röfo-Fortschritte auf dem Gebiet der Röntgenstrahlen und der bildgebenden Verfahren, 2017)
Purpose Projects involving collaborations between different institutions require data security via selective de-identification of words or phrases. A semi-automated de-identification tool was developed and evaluated on different types of medical reports natively and after adapting the algorithm to the text structure. Materials and Methods A semi-automated de-identification tool was developed and evaluated for its sensitivity and specificity in detecting sensitive content in written reports. Data from 4671 pathology reports (4105 + 566 in two different formats), 2804 medical reports, 1008 operation reports, and 6223 radiology reports of 1167 patients suffering from breast cancer were de-identified. The content was itemized into four categories: direct identifiers (name, address), indirect identifiers (date of birth/operation, medical ID, etc.), medical terms, and filler words. The software was tested natively (without training) in order to establish a baseline. The reports were manually edited and the model re-trained for the next test set. After manually editing 25, 50, 100, 250, 500 and if applicable 1000 reports of each type re-training was applied. Results In the native test, 61.3 % of direct and 80.8 % of the indirect identifiers were detected. The performance (P) increased to 91.4 % (P25), 96.7 % (P50), 99.5 % (P100), 99.6 % (P250), 99.7 % (P500) and 100 % (P1000) for direct identifiers and to 93.2 % (P25), 97.9 % (P50), 97.2 % (P100), 98.9 % (P250), 99.0 % (P500) and 99.3 % (P1000) for indirect identifiers. Without training, 5.3 % of medical terms were falsely flagged as critical data. The performance increased, after training, to 4.0 % (P25), 3.6 % (P50), 4.0 % (P100), 3.7 % (P250), 4.3 % (P500), and 3.1 % (P1000). Roughly 0.1 % of filler words were falsely flagged. Conclusion Training of the developed de-identification tool continuously improved its performance. Training with roughly 100 edited reports enables reliable detection and labeling of sensitive data in different types of medical reports. Key Points: · Collaborations between different institutions require de-identification of patients' data. · Software-based de-identification of content-sensitive reports grows in importance as a result of 'Big data'. · A de-identification software was developed and tested natively and after training. · The proposed de-identification software worked quite reliably, following training with roughly 100 edited reports. · A final check of the texts by an authorized person remains necessary. Citation Format · Seuss H, Dankerl P, Ihle M et al. Semi-automated De-identification of German Content Sensitive Reports for Big Data Analytics. Fortschr Röntgenstr 2017; 189: 661 - 671.
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Semi-automated delineation of breast cancer tumors and subsequent materialization using three-dimensional printing (rapid prototyping) - Schulz-Wendtland, Rüdiger; Harz, Markus; Meier-Meitinger, Martina; Brehm, Barbara; Wacker, Till; Hahn, Horst K.; Wagner, Florian; Wittenberg, Thomas; Beckmann, Matthias; Uder, Michael; Fasching, Peter; Emons, Julius (Journal of Surgical Oncology, 2017)
Three-dimensional (3D) printing has become widely available, and a few cases of its use in clinical practice have been described. The aim of this study was to explore facilities for the semi-automated delineation of breast cancer tumors and to assess the feasibility of 3D printing of breast cancer tumors.In a case series of five patients, different 3D imaging methods-magnetic resonance imaging (MRI), digital breast tomosynthesis (DBT), and 3D ultrasound-were used to capture 3D data for breast cancer tumors. The volumes of the breast tumors were calculated to assess the comparability of the breast tumor models, and the MRI information was used to render models on a commercially available 3D printer to materialize the tumors.The tumor volumes calculated from the different 3D methods appeared to be comparable. Tumor models with volumes between 325 mm(3) and 7,770 mm(3) were printed and compared with the models rendered from MRI. The materialization of the tumors reflected the computer models of them.3D printing (rapid prototyping) appears to be feasible. Scenarios for the clinical use of the technology might include presenting the model to the surgeon to provide a better understanding of the tumor's spatial characteristics in the breast, in order to improve decision-making in relation to neoadjuvant chemotherapy or surgical approaches. J. Surg. Oncol. 2017;115:238-242. © 2016 Wiley Periodicals, Inc.
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Serum carbonic anhydrase IX as predictive marker for efficacy of bevacizumab: a biomarker analysis from the GeparQuinto phase III neoadjuvant breast cancer trial - Janning, M.; Mueller,; Vettorazzi, E.; Cubas-Cordova, M.; Gensch,; Ben Batalla,; Eulenburg, Zu C.; Schem, C.; Fasching, Peter; Schnappauf, B.; Karn, Thomas; Fehm, T.; et al. (2016)
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Sex-specific association between prenatal androgenization (second-to-fourth digit length ratio) and frontal brain volumes in adolescents - Lenz, Bernd; Gerhardt, Sarah; Boroumand-Jazi, Rafat; Eichler, Anna; Buchholz, Verena Nadine; Fasching, Peter; Kornhuber, Johannes; Banaschewski, Tobias; Flor, Herta; Guldner, Stella; Prignitz, Maren; Nees, Frauke (European archives of psychiatry and clinical neuroscience, 2022)
Prenatal androgenization associates sex-dependently with behavior and mental health in adolescence and adulthood, including risk-taking, emotionality, substance use, and depression. However, still little is known on how it affects underlying neural correlates, like frontal brain control regions. Thus, we tested whether prenatal androgen load is sex-dependently related to frontal cortex volumes in a sex-balanced adolescent sample. In a cross-sectional magnetic resonance imaging study, we examined 61 adolescents (28 males, 33 females; aged 14 or 16 years) and analyzed associations of frontal brain region volumes with the second-to-fourth digit length ratio (2D:4D), an established marker for prenatal androgenization, using voxel-based morphometry in a region-of-interest approach. Lower 2D:4D (indicative of higher prenatal androgen load) correlated significantly with smaller volumes of the right anterior cingulate cortex (r-ACC; beta = 0.45) in male adolescents and with larger volumes of the left inferior frontal gyrus orbital part (l-IFGorb; beta = - 0.38) in female adolescents. The regression slopes of 2D:4D on the r-ACC also differed significantly between males and females. The study provides novel evidence that prenatal androgenization may influence the development of the frontal brain in a sex- and frontal brain region-specific manner. These effects might contribute to the well-known sex differences in risk-taking, emotionality, substance use, and depression. Future research is needed to elucidate the role of prenatal androgenization within the biopsychosocial model.
CRIS-Team WoS Importer:2022-12-23

Sexual Behavior, Desire, and Psychosexual Experience in Gynephilic and Androphilic Trans Women: A Cross-Sectional Multicenter Study - Laube, Jelena S.; Auer, Matthias K.; Biedermann, Sarah V.; Schröder, Johanna; Hildebrandt, Thomas; Nieder, Timo O.; Briken, Peer; Fuss, Johannes (Journal of Sexual Medicine, 2020)
Background: One of the most prominent etiological theories of gender incongruence in trans women proposes a paraphilic erotic target location error (ie, autogynephilia) as a causal factor in gynephilic (ie, exclusively gynephilic and bisexual) trans women. We hypothesized that a paraphilic erotic target location should manifest itself in various aspects of sexual behavior, solitary and dyadic sexual desire, and psychosexual experience. Aim: To compare sexual behavior, sexual desire, and psychosexual experience of exclusively gynephilic and bisexual trans women with that of androphilic trans women to explore whether their sexuality differs substantially. Methods: Trans women diagnosed with gender dysphoria (Diagnostic and Statistical Manual of Mental Disorders–5) were recruited at 4 transgender healthcare centers in Germany. The present study analyzed items on sexual behavior, desire, and experience of a self-report questionnaire, collected as part of a cross-sectional multicenter study. Main Outcomes: Multiple aspects of sexuality were examined using self-constructed items. Sexual desire was measured using the Sexual Desire Inventory and psychosexual experience using the Multidimensional Sexuality Questionnaire. Results: Significantly more exclusively gynephilic than androphilic trans women reported a history of sexual arousal in relation to cross-dressing. However, little evidence was found that gynephilic and androphilic sexual desire, behavior, and psychosexual experience differ profoundly. Interestingly, a statistically non-significant trend indicated that gynephilic trans women who had not yet undergone gender affirming surgery showed the highest levels of sexual desire (solitary and dyadic), whereas the opposite was the case for androphilic trans women. Clinical Translation: Data of this study indicate that sexual orientation does not appear to be a good predicator for sexual behavior, desire, and psychosexual experience in trans women. Strengths and Limitations: We investigated sexual desire and experience using standardized and evaluated measures such as the Sexual Desire Inventory and Multidimensional Sexuality Questionnaire. Future studies with a larger sample size should investigate how different gender affirming medical intervention might have diverging influences on sexual behavior, desire, and experience. Conclusion: Ultimately, this study found little evidence for the hypothesis that sexual behavior, sexual desire, and psychosexual experience differ substantially in gynephilic (exclusively gynephilic and bisexual) and androphilic trans women. Laube JS, Auer M, Biedermann SV, et al. Sexual Behavior, Desire, and Psychosexual Experience in Gynephilic and Androphilic Trans Women: A Cross-Sectional Multicenter Study. J Sex Med 2020;XX:XXX–XXX.
CRIS-Team Scopus Importer:2020-03-20
Keywords: Autogynephilia; Gender Dysphoria; Gender Incongruence; Male To Female; Sexual Orientation; Transgender

Shared genetics underlying epidemiological association between endometriosis and ovarian cancer - Lu, Yi; Cuellar-Partida, Gabriel; Painter, Jodie N.; Nyholt, Dale R.; Morris, Andrew P.; Fasching, Peter A.; Hein, Alexander; Burghaus, Stefanie; Beckmann, Matthias; Lambrechts, Diether; Van Nieuwenhuysen, Els; Vergote, Ignace; et al. (Human Molecular Genetics, 2015)
Epidemiological studies have demonstrated associations between endometriosis and certain histotypes of ovarian cancer, including clear cell, low-grade serous and endometrioid carcinomas. We aimed to determine whether the observed associations might be due to shared genetic aetiology. To address this, we used two endometriosis datasets genotyped on common arrays with full-genome coverage (3194 cases and 7060 controls) and a large ovarian cancer dataset genotyped on the customized Illumina Infinium iSelect (iCOGS) arrays (10 065 cases and 21 663 controls). Previous work has suggested that a large number of genetic variants contribute to endometriosis and ovarian cancer (all histotypes combined) susceptibility. Here, using the iCOGS data, we confirmed polygenic architecture for most histotypes of ovarian cancer. This led us to evaluate if the polygenic effects are shared across diseases. We found evidence for shared genetic risks between endometriosis and all histotypes of ovarian cancer, except for the intestinal mucinous type. Clear cell carcinoma showed the strongest genetic correlation with endometriosis (0.51, 95% CI = 0.18-0.84). Endometrioid and low-grade serous carcinomas had similar correlation coefficients (0.48, 95% CI = 0.07-0.89 and 0.40, 95% CI = 0.05-0.75, respectively). High-grade serous carcinoma, which often arises from the fallopian tubes, showed a weaker genetic correlation with endometriosis (0.25, 95% CI = 0.11-0.39), despite the absence of a known epidemiological association. These results suggest that the epidemiological association between endometriosis and ovarian adenocarcinoma may be attributable to shared genetic susceptibility loci.
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Shared heritability and functional enrichment across six solid cancers - Jiang, Xia; Finucane, Hilary K.; Schumacher, Fredrick R.; Schmit, Stephanie L.; Tyrer, Jonathan P.; Han, Younghun; Michailidou, Kyriaki; Lesseur, Corina; Kuchenbaecker, Karoline B.; Dennis, Joe; Conti, David V.; Casey, Graham; et al. (Nature Communications, 2019)
Quantifying the genetic correlation between cancers can provide important insights into the mechanisms driving cancer etiology. Using genome-wide association study summary statistics across six cancer types based on a total of 296,215 cases and 301,319 controls of European ancestry, here we estimate the pair-wise genetic correlations between breast, colorectal, head/neck, lung, ovary and prostate cancer, and between cancers and 38 other diseases. We observed statistically significant genetic correlations between lung and head/neck cancer (r g = 0.57, p = 4.6 × 10 −8 ), breast and ovarian cancer (r g = 0.24, p = 7 × 10 −5 ), breast and lung cancer (r g = 0.18, p =1.5 × 10 −6 ) and breast and colorectal cancer (r g = 0.15, p = 1.1 × 10 −4 ). We also found that multiple cancers are genetically correlated with non-cancer traits including smoking, psychiatric diseases and metabolic characteristics. Functional enrichment analysis revealed a significant excess contribution of conserved and regulatory regions to cancer heritability. Our comprehensive analysis of cross-cancer heritability suggests that solid tumors arising across tissues share in part a common germline genetic basis.
CRIS-Team Scopus Importer:2019-05-02

SHEAR STRESS-DEPENDENT EXPRESSION OF GLYPICAN-4 AND HEPARAN SULFATE IN DIFFERENT PRIMARY HUMAN ENDOTHELIAL CELLS - Hug, K.; Tauchi, M.; Raaz-Schrauder, Dorette; Stumpfe, F.; Achenbach, Stephan; Dietel-Schor, B.; Urschel, K. (ATHEROSCLEROSIS, 2019)
CRIS-Team WoS Importer:2019-09-10

Shear stress dependent expression of glypican-4 and heparan sulfate in human endothelial cells - Urschel, K.; Hug, K.; Raaz-Schrauder, Dorette; Stumpfe, F. M.; Tauchi, M.; Achenbach, Stephan; Dietel-Schor, B. (EUROPEAN HEART JOURNAL, 2018)
CRIS-Team WoS Importer:2019-03-15

Shifting cancer care towards Multidisciplinarity: the cancer center certification program of the German cancer society - Kowalski, Christoph; Graeven, Ullrich; Von Kalle, Christof; Lang, Hauke; Beckmann, Matthias; Blohmer, Jens-Uwe; Burchardt, Martin; Ehrenfeld, Michael; Fichtner, Jan; Grabbe, Stephan; Hoffmann, Hans; Iro, Heinrich; et al. (BMC Cancer, 2017)
BACKGROUND: Over the last decades numerous initiatives have been set up that aim at translating the best available medical knowledge and treatment into clinical practice. The inherent complexity of the programs and discrepancies in the terminology used make it difficult to appreciate each of them distinctly and compare their specific strengths and weaknesses. To allow comparison and stimulate dialogue between different programs, we in this paper provide an overview of the German Cancer Society certification program for multidisciplinary cancer centers that was established in 2003. MAIN BODY: In the early 2000s the German Cancer Society assessed the available information on quality of cancer care in Germany and concluded that there was a definite need for a comprehensive, transparent and evidence-based system of quality assessment and control. This prompted the development and implementation of a voluntary cancer center certification program that was promoted by scientific societies, health-care providers, and patient advocacy groups and based on guidelines of the highest quality level (S3). The certification system structures the entire process of care from prevention to screening and multidisciplinary treatment of cancer and places multidisciplinary teams at the heart of this program. Within each network of providers, the quality of care is documented using tumor-specific quality indicators. The system started with breast cancer centers in 2003 and colorectal cancer centers in 2006. In 2017, certification systems are established for the majority of cancers. Here we describe the rationale behind the certification program, its history, the development of the certification requirements, the process of data collection, and the certification process as an example for the successful implementation of a voluntary but powerful system to ensure and improve quality of cancer care. CONCLUSION: Since 2003, over 1 million patients had their primary tumors treated in a certified center. There are now over 1200 sites for different tumor entities in four countries that have been certified in accordance with the program and transparently report their results from multidisciplinary treatment for a substantial proportion of cancers. This led to a fundamental change in the structure of cancer care in Germany and neighboring countries within one decade.
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Shifts in Macrophage as a prognostic Biomarker in Patients with luminal Breast Cancer - A Confirmatory Study - Schnellhardt, Sören; Segelhorst, Sarah; Erber, Ramona; Daniel, Christoph; Hartmann, Arndt; Fasching, Peter; Beckmann, Matthias; Fietkau, Rainer; Distel, Luitpold; Rübner, Matthias (STRAHLENTHERAPIE UND ONKOLOGIE, 2021)
CRIS-Team WoS Importer:2021-07-16

Short Report on the Commission Work Financing Commission - successful work continues! - Renner, Stefan; Wallwiener, Diethelm; Beckmann, Matthias (Geburtshilfe und Frauenheilkunde, 2016)
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Should Breast Cancer Surgery Be Done in an Outpatient Setting?: Health Economics From the Perspective of Service Providers - Formago, Margaret; Schrauder, Michael G.; Rauh, Claudia; Hack, Carolin; Jud, Sebastian; Hildebrandt, Thomas; Schulz-Wendtland, Rüdiger; Frentz, S.; Graubert, S.; Beckmann, Matthias; Lux, Michael P. (Geburtshilfe und Frauenheilkunde, 2017)
INTRODUCTION: The care of patients with breast cancer is extremely complex and requires interdisciplinary care in certified facilities. These specialized facilities provide numerous services without being correspondingly remunerated. The question whether breast cancer surgery should be performed in an outpatient setting to reduce costs is increasingly being debated. This study compares inpatient surgical treatment with a model of the same surgery performed on an outpatient basis to examine the potential financial impact. MATERIAL AND METHODS: A theoretical model was developed and the DRG fees for surgical interventions to treat primary breast cancer were calculated. A theoretical 1-day DRG was then calculated to permit comparisons with outpatient procedures. The costs of outpatient surgery were calculated based on the remuneration rates of the AOP (Outpatient Surgery) Contract and the EBM (Uniform Assessment Scale) and compared to the costs of the 1-day DRG. RESULTS: The DRG fee for both breast-conserving surgery and mastectomy is higher than the fee paid in the context of the EBM system, although the same procedures were carried out in both systems. If a hospital were to carry out breast-conserving surgery as an outpatient procedure, the fee would be € 1313.81; depending on the type of surgery, the hospital would therefore only receive between 39.20% and 52.82% of the DRG fee. This was the case even for a 1-day treatment. Compared to the real DRG fees the difference would be even more striking. CONCLUSION: Carrying out breast cancer surgery as an outpatient procedure would result in a significant shortfall of revenues. Additional services from certified centers, such as the interdisciplinary planning of treatment, psycho-oncological and social-medical care with the involvement of relatives, detailed documentation, etc., which are currently provided without surcharge or adequate remuneration, could no longer be maintained. The quality of processes and excellent results which have been achieved and ultimately the care given by certified facilities would be significantly at risk.
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Signal decomposition for X-ray dark-field imaging - Käppler, Sebastian; Bayer, Florian; Weber, Thomas; Maier, Andreas; Anton, Gisela; Hornegger, Joachim; Beckmann, Matthias; Fasching, Peter; Hartmann, Arndt; Heindl, Felix; Michel, Thilo; Oezguel, Gueluemser; et al. (MICCAI 2014, 2014)
Grating-based X-ray dark-field imaging is a new imaging modality. It allows the visualization of structures at micrometer scale due to small-angle scattering of the X-ray beam. However, reading darkfield images is challenging as absorption and edge-diffraction effects also contribute to the dark-field signal, without adding diagnostic value. In this paper, we present a novel–and to our knowledge the first–algorithm for isolating small-angle scattering in dark-field images, which greatly improves their interpretability. To this end, our algorithm utilizes the information available from the absorption and differential phase images to identify clinically irrelevant contributions to the dark-field image. Experimental results on phantom and ex-vivo breast data promise a greatly enhanced diagnostic value of dark-field image
EVALuna2:6632

Simultaneous amniotic membrane patch in high-risk keratoplasty - Seitz, Berthold; Das, Sujata; Sauer, Rolf; Hofmann-Rummelt, Carmen; Beckmann, Matthias; Kruse, Friedrich (Cornea, 2011)
To analyze the short- and intermediate-term results of simultaneous transplantation of amniotic membrane with high-risk keratoplasty.Between January 2002 and February 2004, a simultaneous amniotic membrane patch was transplanted with penetrating keratoplasty in 16 eyes of 16 patients. In 13 eyes, a soft contact lens was applied afterward. Corneal perforation was present in 10 of 14 eyes with emergency keratoplasty. Five patients received systemic immunosuppressive medication for 4-6 months after penetrating keratoplasty.The amniotic membrane patch fell off after 8 ± 3 (range: 4-14) days without residual tissue except in 1 case. In 15 of 16 eyes, the epithelium was completely closed after 10 ± 8 (range: 4-30) days. In 3 eyes, recurrence of the epithelial defect occurred after 3-6 months. During a follow-up period of 18 ± 6 months, 13 of 16 corneal grafts were clear.Simultaneous amniotic membrane transplantation and penetrating keratoplasty may improve the prognosis of corneal graft in eyes with risk of epithelial healing problems.
EVALuna2:17178

Single deepest vertical pocket or amniotic fluid index as evaluation test for predicting adverse pregnancy outcome (SAFE trial): a multicenter, open-label, randomized controlled trial - Kehl, Sven; Schelkle, A.; Thomas, A.; Puhl, A.; Meqdad, K.; Tuschy, B.; Berlit, S.; Weiss, C.; Bayer, C.; Heimrich, J.; Dammer, U.; Raabe, E.; et al. (Ultrasound in Obstetrics & Gynecology, 2016)
OBJECTIVE: To determine whether the amniotic fluid index (AFI) or the single deepest vertical pocket (SDP) technique for estimating amniotic fluid volume is superior for predicting adverse pregnancy outcome. METHODS: This was a multicenter randomized controlled trial including 1052 pregnant women with a term singleton pregnancy across four hospitals in Germany. Women were assigned randomly, according to a computer-generated allocation sequence, to AFI or SDP measurement for estimation of amniotic fluid volume. Oligohydramnios was defined as AFI ≤ 5 cm or the absence of a pocket measuring at least 2 × 1 cm. The diagnosis of oligohydramnios was followed by labor induction. The primary outcome measure was postpartum admission to a neonatal intensive care unit. Further outcome parameters were the rates of diagnosis of oligohydramnios and induction of labor (for oligohydramnios or without specific indication), and mode of delivery. RESULTS: Postpartum admission to a neonatal intensive care unit was similar between groups (4.2% (n = 21) vs 5.0% (n = 25); relative risk (RR), 0.85 (95% CI, 0.48-1.50); P = 0.57). In the AFI group, there were more cases of oligohydramnios (9.8% (n = 49) vs 2.2% (n = 11); RR, 4.51 (95% CI, 2.2-8.57); P < 0.01) and more cases of labor induction for oligohydramnios (12.7% (n = 33) vs 3.6% (n = 10); RR, 3.50 (95% CI, 1.76-6.96); P < 0.01) than in the SDP group. Moreover, an abnormal cardiotocography was seen more often in the AFI group than in the SDP group (32.3% (n = 161) vs 26.2% (n = 132); RR, 1.23 (95% CI, 1.02-1.50); P = 0.03). The other outcome measures were not significantly different between the two groups. CONCLUSIONS: Use of the AFI method increased the rate of diagnosis of oligohydramnios and labor induction for oligohydramnios without improving perinatal outcome. The SDP method is therefore the favorable method to estimate amniotic fluid volume, especially in a population with many low-risk pregnancies. Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd.
EVALuna2:32976

Single Deepest Vertical Pocket or Amniotic Fluid Index as Evaluation Test for Predicting Adverse Pregnancy Outcome (SAFE Trial): A Multicenter, Open-Label, Randomized Controlled Trial EDITORIAL COMMENT - Kehl, Sven; Schelkle, A.; Thomas, A.; Puhl, A.; Meqdad, K.; Tuschy, B.; Berlit, S.; Weiss, C.; Bayer, C.; Heimrich, J.; Dammer, U.; Raabe, E.; et al. (Obstetrical & Gynecological Survey, 2016)
One of the important aspects of fetal well-being assessment is amniotic fluid volume, lack of which leads to oligohydramnios and consequently adverse perinatal outcomes. Amniotic fluid estimation by ultrasound can be performed by assessment of the amniotic fluid index (AFI) or the single deepest vertical pocket (SDP) technique. This study aimed to investigate the best technique for amniotic fluid volume estimation to predict adverse pregnancy outcomes in both high-and low-risk pregnancies. In a randomized controlled trial (RCT), participants from 4 hospitals in Germany were allocated randomly to AFI or SDP measurement (1: 1). Oligohydramnios was defined by an AFI 5 cm or less or by the absence of an SDP measuring less than 2 x 1 cm. The primary outcome measure was admission to a neonatal intensive care unit (NICU) following childbirth, and other outcome measures included perinatal death, oligohydramnios, labor induction (for oligohydramnios or without specific indication), umbilical artery pH less than 7.10, 5-minute Apgar score of less than 7, meconium-stained amniotic fluid, abnormal cardiotocography, need for fetal scalp blood sampling, assisted vaginal delivery (for fetal distress or without specified indication), and cesarean delivery (for and without fetal distress). Statistical analyses were performed using the Student t test, Mann-Whitney U test,.2 test, or Fisher exact test and a logistic regression analysis or a 2-way analysis of variance. There were fewer women with gestational diabetes and a previous cesarean delivery in the AFI group among the 1002 women analyzed. Women with a high-risk pregnancy were older, shorter, and more overweight than women with a low-risk pregnancy. Postnatal admission rates to the NICU (4.2% vs 5%; relative risk [ RR], 0.85; 95% confidence interval [ CI], 0.481.50) and rate of arterial pH less than 7.10 were similar between the 2 groups (1.6% vs 3%; RR, 0.54; 95% CI, 0.23-1.26). There weremore participants with oligohydramnios (9.8% vs 2.2%; RR, 4.51; 95% CI, 2.37-8.57), more labor inductions for oligohydramnios (12.7% vs 3.6%; RR, 3.50; 95% CI, 1.76-6.96), and higher occurrences of abnormal cardiotocography (32.3% vs 26.2%; RR, 1.23; 95% CI, 1.02-1.50) in the AFI group than in the SDP group. More cases of oligohydramnios and labor inductions for oligohydramnios were found in low-risk pregnancies measured by the AFI method than by the SDP technique, and a lower arterial pH was observed in the AFI group compared with the SDP group in high-risk pregnancies. The AFI technique increased the diagnosis rate of oligohydramnios without improvement in perinatal outcome; hence, the SDP technique is preferred over AFI especially in low-risk pregnancies.
EVALuna2:32953

Single nucleotide polymorphism D1853N of the ATM gene may alter the risk for breast cancer - Schrauder, M.; Frank, S.; Strissel, Pamela; Lux, Michael P.; Bani, Mayada; Rauh, C.; Sieber, Cornel; Heusinger, K.; Hartmann, Arndt; Schulz-Wendtland, Rüdiger; Strick, Reiner; Beckmann, Matthias; et al. (Journal of Cancer Research and Clinical Oncology, 2008)
Purpose Various ATM (ataxia telangiectasia-mutated) mutations and polymorphisms have been reported to be associated with an increased breast cancer risk. Recent studies have produced contradictory results regarding the association between ATM genetic variants and breast cancer risk.Materials and methods The common ATM polymorphism 5557G > A (p.D1853N) (rs1801516), previously suggested to be associated with bilateral breast cancer, was analyzed using real-time PCR in 514 unselected patients with breast cancer and 511 age-matched healthy control individuals. DNA was obtained from peripheral blood draw.Results The ATM genotype was weakly associated with the risk for breast cancer (P = 0.04 for the overall test). The odds ratio for women with a heterozygous genotype was 0.70 (95% CI, 0.52-0.94) and for the homozygous variant 0.63 (95% CI, 0.27-1.49). Disease-free survival and overall survival showed no significant association with specific genotypes.Conclusions The results of this study might suggest a minor association between polymorphism 5557G > A and a reduced risk of breast cancer.
Keywords: TM gene variants; polymorphism; breast cancer; DNA damage; epidemiology; association

Situation of Adolescent Contraceptive Use in Germany - Oppelt, Patricia; Fahlbusch, Christine; Heusinger, Katharina; Lotz, Laura; Dittrich, Ralf; Baier, Friederike (Geburtshilfe und Frauenheilkunde, 2018)
Introduction Would adolescent girls in Germany choose a different method of contraception to the combined oral contraceptive if provided with the appropriate information? Is there a need for long-acting contraception among our adolescent girls? How satisfied are female patients with the information they receive at their respective gynaecology practices, and how much do the girls know about different methods of contraception? Materials and Methods In the study "Thinking About Needs in COntraception" (TANCO), not only female patients, but also their respective gynaecologists were surveyed online about current methods of contraception, their satisfaction with these methods, and also their level of knowledge concerning the individual methods of contraception, the situation related to advice about different contraceptive options and their general satisfaction with gynaecological care. This article presents the data from the subset of adolescent girls aged 14 to 19 years (n = 2699) out of the total of 18 521 women surveyed. Results The girls surveyed were familiar with at least the name of more than five different methods of contraception (average 5.3). The doctors assumed that the respondents would know only 4.2 different methods. When asked explicitly about how the individual methods of contraception work, clear deficits became evident. This applies not only to the entire population of respondents, but also the users of the respective contraceptive method. In addition, a strong interest in long-acting contraception emerged from the survey, particularly among young women. Discussion The data from the TANCO study reveal a clear discrepancy between the existing contraception almost exclusively in the form of the contraceptive pill and the contraceptive options considered by adolescent girls if they are thoroughly informed. The need for education into alternatives to the pill is high, as is the willingness to use such alternatives after receiving information - much higher than the figures suggested by the gynaecologists.
EVALuna2:210080

Smartphone-Based Colorimetric Analysis of Urine Test Strips for At-Home Prenatal Care - Flaucher, Madeleine; Nissen, Michael; Jäger, Katharina; Titzmann, Adriana; Pontones, Constanza; Hübner, Hanna; Fasching, Peter; Beckmann, Matthias; Gradl, Stefan; Eskofier, Björn (IEEE Journal of Translational Engineering in Health and Medicine, 2022)
Objective: Clinical urine tests are a key component of prenatal care. As of now, urine test strips are evaluated through a time consuming, often error-prone and operator-dependent visual color comparison of test strips and reference cards by medical staff. Methods and procedures: This work presents an automated pipeline for urinalysis with urine test strips using smartphone camera images in home environments, combining several image processing and color combination techniques. Our approach is applicable to off-the-shelf test strips in home conditions with no additional hardware required. For development and evaluation of our pipeline we collected image data from two sources: i) A user study (26 participants, 150 images) and ii) a lab study (135 images). Results: We trained a region-based convolutional neural network that is able to detect the urine test strip location and orientation in images with a wide variety of light conditions, backgrounds and perspectives with an accuracy of 85.5%. The reference card can be robustly detected through a feature matching approach in 98.6% of the images. Color comparison by Hue channel (0.81 F1-Score), Matching factor (0.80 F1-Score) and Euclidean distance (0.70 F1-Score) were evaluated to determine the urinalysis results. Conclusion: We show that an automated smartphone-based colorimetric analysis of urine test strips in a home environment is feasible. It facilitates examinations and provides the possibility to shift care into an at-home environment. Clinical impact: The findings demonstrate that routine urine examinations can be transferred into the home environment using a smartphone. Simultaneously, human error is avoided, accuracy is increased and medical staff is relieve

Smartphone pregnancy apps: systematic analysis of features, scientific guidance, commercialization, and user perception - Nissen, Michael; Huang, Shih-Yuan; Jäger, Katharina; Flaucher, Madeleine; Titzmann, Adriana; Bleher, Hannah; Pontones, Constanza; Hübner, Hanna; Danzberger, Nina; Fasching, Peter; Eskofier, Björn; Leutheuser, Heike (BMC Pregnancy and Childbirth, 2024)
Background Over 50% of pregnant women use pregnancy applications (apps). Some app s lack credibility, information accuracy, and evidence-based clinical advice, containing potentially harmful functionality. Previous studies have only conducted a limited analysis of pregnancy app functionalities, expert involvement/evidence-based content, used commercialization techniques, and user perception. Methods We used the keyword “pregnancy” to scrape (automatically extract) apps and app information from Apple App Store and Google Play. Unique functionalities were derived from app descriptions and user reviews. App descriptions were screened for evidence-based content and expert involvement, and apps were subsequently analyzed in detail. Apps were opened and searched for used commercialization techniques, such as advertisements or affiliate marketing. Automated text analysis (natural language processing) was used on app reviews to assess users’ perception of evidence-based content/expert involvement and commercialization techniques. Results In total, 495 apps were scraped. 226 remained after applying exclusion criteria. Out of these, 36 represented 97%/88% of the total market share (Apple App Store/Google Play), and were thus considered for review. Overall, 49 distinct functionalities were identified, out of which 6 were previously unreported. Functionalities for fetal kick movement counting were found. All apps are commercial. Only 15 apps mention the involvement of medical experts. 10.3% of two-stars user reviews include commercial topics, and 0.6% of one-/two-/three-/five stars user reviews include references to scientific content accuracy. Conclusion Problematic features and inadequate advice continue to be present in pregnancy apps. App developers should adopt an evidence-based development approach and avoid implementing as many features as possible, potentially at the expense of their quality or over-complication (“feature creep”). Financial incentives, such as grant programs, could support adequate content quality. Caregivers play a key role in pregnant individuals’ decision-making, should be aware of potential dangers, and could guide them to trustworthy app

Smart sensing in pregnancy: a survey-based evaluation of readiness to use wearable sensory applications in prenatal care - Weidenthaler, Filip; Danzberger, Nina; Pontones, Constanza; Titzmann, Adriana; Hein, Alexander; Beckmann, Matthias; Fasching, Peter; Huebner, H. (GEBURTSHILFE UND FRAUENHEILKUNDE, 2022)
CRIS-Team WoS Importer:2022-11-04

Sniper: A novel hypermethylation biomarker panel for liquid biopsy based early breast cancer detection - Mijnes, Jolein; Tiedemann, Janina; Eschenbruch, Julian; Gasthaus, Janina; Bringezu, Sarah; Bauerschlag, Dirk; Maass, Nicolai; Arnold, Norbert; Weimer, Jörg; Anzeneder, Tobias; Fasching, Peter; Rübner, Matthias; et al. (Oncotarget, 2019)
Introduction: Mammography is the gold standard for early breast cancer detection, but shows important limitations. Blood-based approaches on basis of cell-free DNA (cfDNA) provide minimally invasive screening tools to characterize epigenetic alterations of tumor suppressor genes and could serve as a liquid biopsy, complementing mammography. Methods: Potential biomarkers were identified from The Cancer Genome Atlas (TCGA), using HumanMethylation450-BeadChip data. Promoter methylation status was evaluated quantitatively by pyrosequencing in a serum test cohort (n = 103), a serum validation cohort (n = 368) and a plasma cohort (n = 125). Results: SPAG6, NKX2-6 and PER1 were identified as novel biomarker candidates. ITIH5 was included on basis of our previous work. In the serum test cohort, a panel of SPAG6 and ITIH5 showed 63% sensitivity for DCIS and 51% sensitivity for early invasive tumor (pT1, pN0) detection at 80% specificity. The serum validation cohort revealed 50% sensitivity for DCIS detection on basis of NKX2-6 and ITIH5. Furthermore, an inverse correlation between methylation frequency and cfDNA concentration was uncovered. Therefore, markers were tested in a plasma cohort, achieving a 64% sensitivity for breast cancer detection using SPAG6, PER1 and ITIH5. Conclusions: Although liquid biopsy remains challenging, a combination of SPAG6, NKX2-6, ITIH5 and PER1 (SNiPER) provides a promising tool for blood-based breast cancer detection.
CRIS-Team Scopus Importer:2019-12-03
Keywords: Breast cancer; Discriminative CpG dinucleotides; Early detection; Hypermethylation; Liquid biopsy

SNP-SNP interaction analysis of NF-?B signaling pathway on breast cancer survival - Jamshidi, Maral; Fagerholm, Rainer; Khan, Sofia; Aittomaki, Kristiina; Czene, Kamila; Darabi, Hatef; Li, Jingmei; Andrulis, Irene L.; Chang-Claude, Jenny; Devilee, Peter; Fasching, Peter; Michailidou, Kyriaki; et al. (Oncotarget, 2015)
In breast cancer, constitutive activation of NF-?B has been reported, however, the impact of genetic variation of the pathway on patient prognosis has been little studied. Furthermore, a combination of genetic variants, rather than single polymorphisms, may affect disease prognosis. Here, in an extensive dataset (n = 30,431) from the Breast Cancer Association Consortium, we investigated the association of 917 SNPs in 75 genes in the NF-?B pathway with breast cancer prognosis. We explored SNP-SNP interactions on survival using the likelihood-ratio test comparing multivariate Cox' regression models of SNP pairs without and with an interaction term. We found two interacting pairs associating with prognosis: patients simultaneously homozygous for the rare alleles of rs5996080 and rs7973914 had worse survival (HRinteraction 6.98, 95% CI=3.3-14.4, P=1.42E-07), and patients carrying at least one rare allele for rs17243893 and rs57890595 had better survival (HRinteraction 0.51, 95% CI=0.3-0.6, P = 2.19E-05). Based on in silico functional analyses and literature, we speculate that the rs5996080 and rs7973914 loci may affect the BAFFR and TNFR1/TNFR3 receptors and breast cancer survival, possibly by disturbing both the canonical and non-canonical NF-?B pathways or their dynamics, whereas, rs17243893-rs57890595 interaction on survival may be mediated through TRAF2-TRAIL-R4 interplay. These results warrant further validation and functional analyses.
EVALuna2:17574

Socioeconomic status and depression during and after pregnancy in the Franconian Maternal Health Evaluation Studies (FRAMES) - Hein, Alexander; Rauh, Claudia; Engel, Anne; Häberle, Lothar; Dammer, Ulf; Voigt, Franziska; Fasching, Peter; Faschingbauer, Florian; Burger, Pascal; Beckmann, Matthias; Kornhuber, Johannes; Goecke, Tamme W. (Archives of Gynecology and Obstetrics, 2014)
Depression during and after pregnancy can have a negative impact on women's quality of life and on the development of the newborn child. Interventions have been shown to have a positive influence on both mothers and children. Predictive factors for depressive symptoms might possibly be able to identify groups that are at high risk. The aim of this study was to investigate the value of socioeconomic factors in predicting depressive symptoms during and after pregnancy.Depressiveness was measured using the German version of the 10-item Edinburgh Postnatal Depression Scale (EPDS) at three time-points, in a prospective cohort study (n = 1,100). Visit 1 (Q1) was at study entry in the third trimester of the pregnancy, visit 2 (Q2) was shortly after birth, and visit 3 (Q3) was 6-8 months after birth. Depression scores were associated with socioeconomic factors and time in linear mixed models.Parity status, education status, monthly income, residential property status, and partnership status, as well as interactions between them, were found to be predictive factors for EPDS scores. The strongest factor influencing depressive symptoms was partnership status. Women who did not have an intact partnership had EPDS scores that were on average four points higher than in women with a partner at all three study visits (P < 0.000001).Socioeconomic factors define subgroups that have different depression scores during and after pregnancy. Partnership status appears to be one of the most important influencing factors and could be useful for identifying women who should be offered an intervention to prevent possible negative effects on the mother or child.
EVALuna2:17434

Sonographic weight estimation in fetal macrosomia: influence of the time interval between estimation and delivery - Faschingbauer, Florian; Dammer, U.; Raabe, E.; Schneider, M.; Faschingbauer, Cornelia; Schmid, M.; Mayr, Andreas; Schild, R. L.; Beckmann, Matthias; Kehl, Sven (Archives of Gynecology and Obstetrics, 2015)
To evaluate the influence of the time interval between examination and delivery on the accuracy of sonographic weight estimation (WE) in fetal macrosomia.896 singleton pregnancies (birth weight > 4,000 g) with a total of 1,281 sonographic weight estimations were included in this retrospective cohort study. Fetuses were divided into six groups with regard to the time interval between estimation and delivery: group 1: scan-to-delivery interval: 0 days; group 2: scan-to-delivery interval: 1-3 days; group 3: scan-to-delivery interval: 4-7 days; group 4: scan-to-delivery interval: 8-14 days; group 5: scan-to-delivery interval: 15-21 days; group 6: scan-to-delivery interval: 22-42 days. The accuracy of WE was compared between five commonly used formulas using means of percentage errors (MPE), random error, medians of absolute percentage errors (MAPE), and proportions of estimates within 10 % of actual birth weight.Significant differences were found between the time interval groups with regard to MAPE and MPE values (p < 0.001). All formulas showed a systematic underestimation of fetal weight (negative MPEs) (p < 0.05). MPE values were closest to zero in time interval group 1 and 2. From group 3 to 6, a continuous decrease was observed. The lowest MAPE was found with the Merz formula in group 1 and 2. Values increased continuously from group 3 to 6. Differences between time interval group one and three did not reach statistical significance.WE in fetal macrosomia shows the best results when examinations are performed within 7 days before delivery, using the formula of Merz et al. Accuracy significantly decreases after this time period.
EVALuna2:5469

Sonographic Weight Estimation in Small-for-Gestational-Age Fetuses - Dammer, U.; Raabe, E.; Kehl, Sven; Schmid, M.; Mayr, Andreas; Schild, R. L.; Beckmann, Matthias; Faschingbauer, Florian (Ultraschall in der Medizin, 2015)
Purpose: To determine the accuracy of sonographic weight estimation (WE) for small-for-gestational-age (SGA) fetuses, and to further differentiate the evaluation between symmetric and asymmetric SGA fetuses. Materials and Methods: The accuracy of WE in SGA fetuses (n = 898) was evaluated using 14 sonographic models and was further differentiated between symmetric (n = 750) and asymmetric (n = 148) SGA fetuses. SGA fetuses were considered to be asymmetric with a head circumference to abdominal circumference ratio above the 95th percentile. The accuracy of the different formulas was compared using means of percentage errors (MPE), medians of absolute percentage errors (MAPE), and proportions of estimates within 10 % of actual birth weight. Results: Results for the subgroup of asymmetric SGA fetuses differed significantly from the subgroup of symmetric SGA fetuses. MPE values were closer to zero with most of the formulas in the asymmetric SGA group. Apart from the Siemer, Shepard, Merz and Warsof equations, all formulas showed an underestimation of fetal weight in asymmetric SGA fetuses. In contrast, in the symmetric SGA group, all of the formulas commonly used for fetuses in a normal weight range showed a systematic overestimation of fetal weight. Overall the best accuracy was achieved by using the Sabbagha equation (MPE 1.7 %; SD 9.0 %; MAPE: 6.0). Conclusion: An accurate WE in SGA fetuses is feasible using the Sabbagha formula. However, one has to be aware of the significant differences in WE between symmetric and asymmetric SGA fetuses.
EVALuna2:5471

Sorafenib in combination with docetaxel as first-line therapy for HER2-negative metastatic breast cancer: Final results of the randomized, double-blind, placebo-controlled phase II MADONNA study - Mavratzas, A.; Baek, S.; Gerber, B.; Schmidt, Marcus; Moebus,; Foerster, F.; Grischke, E. M.; Fasching, Peter; Strumberg, D.; Solomayer, E.; Klare, P.; Windemuth-Kieselbach, C.; et al. (BREAST, 2019)
Background: This multicenter, double-blind phase II study assessed the antitumor activity and toxicity profile of docetaxel with the antiangiogenic multikinase inhibitor sorafenib or matching placebo as a first-line treatment in patients with metastatic or locally advanced HER2-negative breast cancer. Patients and methods: Patients were randomized 1:1 to receive docetaxel 100 mg/m 2 on day 1 every 3 weeks in combination with sorafenib 400 mg bid or placebo on days 2–18 of each cycle until tumor progression, or unacceptable toxicity. Sorafenib/placebo could be continued at the investigator's discretion if docetaxel was stopped due to toxicity. Primary endpoint was progression free survival (PFS). Results: From October 2008 to December 2013, 102 patients were randomized; 98 patients were evaluable. The trial was prematurely terminated due to slow accrual. Due to increased toxicity the dose of docetaxel was reduced to 75 mg/m 2 and an increasing sorafenib dosing schedule was implemented as part of a protocol amendment. The addition of sorafenib to docetaxel did not improve PFS (8.2 vs. 7.3 months for docetaxel/placebo; HR 0.84, log rank p = 0.43), but led to higher rates of early treatment discontinuation. There were no statistically significant differences between sorafenib dosing schedules. Conclusions: Addition of sorafenib to taxane-based first-line chemotherapy in patients with metastatic breast cancer failed to improve PFS and resulted in increased toxicity.
CRIS-Team Scopus Importer:2019-05-09
Keywords: Antiangiogenic agents; Docetaxel; Metastatic breast cancer; Sorafenib

Spatial expression of claudin 18.2 in matched primaries and metastases of tubo-ovarian carcinoma of all subtypes - Wagner, Paul; Gaß, Paul; Pöschke, Patrik; Eckstein, Markus; Gloßner, Laura; Hartmann, Arndt; Beckmann, Matthias; Fasching, Peter; Rübner, Matthias; Emons, Julius; Erber, Ramona (Virchows Archiv, 2024)
Physiologically, claudin 18 splice variant 2 (CLDN18.2) expression is restricted to the gastric epithelium, but its expression has been detected in solid cancers. Zolbetuximab, a chimeric IgG1 antibody targeting CLDN18.2, has demonstrated promising effects in patients suffering from CLDN18.2-positive, HER2-negative locally advanced gastric cancer and is currently being studied further. To date, little is known about CLDN18.2 expression in other histological subtypes of tubo-ovarian carcinoma (TOC) and their matching metastases. Using a cohort of all histological TOC subtypes, we investigated the immunohistochemical (IHC) CLDN18.2 expression in both TOCs (n = 536), their matching metastatic tissue (n = 385) and in 93 metastases without primary. Tissue microarrays comprised both the tumor center and periphery. IHC positivity was defined as biomarker expression of ≥ 75% in tumor cells with moderate-to-strong membranous staining. Overall CLDN18.2 positivity was 4.1% (21/515) in the TOC centers and 3.6% (18/498) in their peripheries. In primaries of mucinous tubo-ovarian carcinoma (MTOC), CLDN18.2 positivity rates were 45% (18/40) and 36.6% (15/41), respectively. Positivity rates for the corresponding metastases were 33% (4/12, center) and 27% (3/11, periphery). The expression was relatively homogenous throughout all tumor sites. With no expression in 99.5% of nonmucinous tumors, CLDN18.2 positivity was almost exclusively seen in the mucinous subtype. In tubo-ovarian carcinoma, CLDN18.2 expression was, with rare exceptions, restricted to the mucinous subtype. Among them, 33% of metastasized MTOCs presented with CLDN18.2 positivity. Hence, CLDN18.2 might display a promising target for personalized therapy in patients with advanced MTOC.
CRIS-Team Scopus Importer:2024-02-16
Keywords: CLDN18.2; Immunohistochemistry; Mucinous tubo-ovarian carcinoma; Targeted therapy; Tubo-ovarian cancer

Spatial Immunephenotypes of Distant Metastases but not Matched Primary Urothelial Carcinomas Predict Response to Immune Checkpoint Inhibition - Erlmeier, Franziska; Klümper, Niklas; Landgraf, Laura; Strissel, Pamela; Strick, Reiner; Sikic, Danijel; Taubert, Helge; Wach, Sven; Geppert, Carol-Immanuel; Bahlinger, Veronika; Breyer, Johannes; Ritter, Manuel; et al. (European Urology, 2022)
Background: The value of programmed cell death ligand-1 (PD-L1) to predict durable responses to immune checkpoint inhibitors (ICIs) in metastatic urothelial carcinoma (mUC) is inconsistent. We hypothesize that the use of archived primary tumor material (PRIM) for PD-L1 testing in clinical trials not properly reflecting the metastatic disease status (MET) contributes to this clinical issue. Objective: To analyze the predictive and prognostic value of PD-L1, spatial immunephenotypes, and major histocompatibility complex class I (MHC-I) determined in patient-matched PRIM/MET. Design, setting, and participants: PD-L1, spatial immunephenotypes, and MHC-I were examined in 154 mUC patients with at least one available pretreatment MET (138 patient-matched PRIM/MET pairs). Outcome measurements and statistical analysis: PD-L1, spatial immunephenotype, and MHC-I status of (patient-matched PRIM and) pretreatment MET were correlated with chemotherapy and ICI response and outcomes. Results and limitations: Discordance rates in patient-matched PRIM/MET were 25/30%, 36%, and 49% for PD-L1 (CPS10/IC5%), immunephenotypes, and MHC-I (loss vs preserved), respectively. Correlations with chemotherapy and ICI responses were observed for immunephenotypes and MHC-I status determined in MET (not for PD-L1 alone), but not in PRIM. In case of ICIs, patients with cytotoxic tumor immune microenvironment (TIME) showed durable responses with disease control rates of 90% and a hazard ratio for disease progression/death of 0.05 (95% confidence interval: 0.01–0.65) versus patients with immunedepleted MET (disease control rate 29%). MET MHC-I status added an incremental value to predict durable ICI responses. Limitations include the partly retrospective design and the lack of MET multisampling on individual patient level. Conclusions: The TIME is subject to substantial dynamics during metastatic evolution. MET immunephenotypes and MHC-I statuses show promising potential to predict chemotherapy and durable ICI responses, while the PRIM TIME does not. Thus, future clinical trials should rather rely on pretreatment MET biopsies reflecting the current immunological disease state than on PRIM. Patient summary: Prediction of chemotherapy and responses to immune checkpoint inhibitors might be possible using representative pretreatment metastatic biopsies.
CRIS-Team Scopus Importer:2022-11-25
Keywords: Immune microenvironment; Immune therapy; Metastatic urothelial cancer; Subtypes; Urothelial cancer

Specific microRNA signatures in exosomes of triple-negative and HER2-positive breast cancer patients undergoing neoadjuvant therapy within the GeparSixto trial - Stevic, Ines; Mueller, Volkmar; Weber, Karsten; Fasching, Peter; Karn, Thomas; Marme, Frederic; Schem, Christian; Stickeler, Elmar; Denkert, Carsten; Van Mackelenbergh, Marion; Salat, Christoph; Schneeweiss, Andreas; et al. (BMC Medicine, 2018)
BACKGROUND: The focus of this study is to identify particular microRNA (miRNA) signatures in exosomes derived from plasma of 435 human epidermal growth factor receptor 2 (HER2)-positive and triple-negative (TN) subtypes of breast cancer (BC). METHODS: First, miRNA expression profiles were determined in exosomes derived from the plasma of 15 TNBC patients before neoadjuvant therapy using a quantitative TaqMan real-time PCR-based microRNA array card containing 384 different miRNAs. Forty-five miRNAs associated with different clinical parameters were then selected and mounted on microRNA array cards that served for the quantification of exosomal miRNAs in 435 BC patients before therapy and 20 healthy women. Confocal microscopy, Western blot, and ELISA were used for exosome characterization. RESULTS: Quantification of 45 exosomal miRNAs showed that compared with healthy women, 10 miRNAs in the entire cohort of BC patients, 13 in the subgroup of 211 HER2-positive BC, and 17 in the subgroup of 224 TNBC were significantly deregulated. Plasma levels of 18 exosomal miRNAs differed between HER2-positive and TNBC subtypes, and 9 miRNAs of them also differed from healthy women. Exosomal miRNAs were significantly associated with the clinicopathological and risk factors. In uni- and multivariate models, miR-155 (p = 0.002, p = 0.003, respectively) and miR-301 (p = 0.002, p = 0.001, respectively) best predicted pathological complete response (pCR). CONCLUSION: Our findings show a network of deregulated exosomal miRNAs with specific expression patterns in exosomes of HER2-positive and TNBC patients that are also associated with clinicopathological parameters and pCR within each BC subtype.
EVALuna2:210019

Spectrum and Frequency of Germline FANCM Protein-Truncating Variants in 44,803 European Female Breast Cancer Cases - Figlioli, Gisella; Billaud, Amandine; Wang, Qin; Bolla, Manjeet K.; Dennis, Joe; Lush, Michael; Kvist, Anders; Adank, Muriel A.; Ahearn, Thomas U.; Antonenkova, Natalia N.; Auvinen, Päivi; Behrens, Sabine; et al. (Cancers, 2023)
FANCM germline protein truncating variants (PTVs) are moderate-risk factors for ER-negative breast cancer. We previously described the spectrum of FANCM PTVs in 114 European breast cancer cases. In the present, larger cohort, we report the spectrum and frequency of four common and 62 rare FANCM PTVs found in 274 carriers detected among 44,803 breast cancer cases. We confirmed that p.Gln1701* was the most common PTV in Northern Europe with lower frequencies in Southern Europe. In contrast, p.Gly1906Alafs*12 was the most common PTV in Southern Europe with decreasing frequencies in Central and Northern Europe. We verified that p.Arg658* was prevalent in Central Europe and had highest frequencies in Eastern Europe. We also confirmed that the fourth most common PTV, p.Gln498Thrfs*7, might be a founder variant from Lithuania. Based on the frequency distribution of the carriers of rare PTVs, we showed that the FANCM PTVs spectra in Southwestern and Central Europe were much more heterogeneous than those from Northeastern Europe. These findings will inform the development of more efficient FANCM genetic testing strategies for breast cancer cases from specific European populations.
CRIS-Team Scopus Importer:2023-07-28
Keywords: breast cancer predisposition; breast cancer risk factors; FANCM PTVs spectrum; protein truncating variants; PTVs

Sperm activating odorous substances in human follicular fluid and vaginal secretion: Identification by gas chromatography-olfactometry and Ca2+ imaging. - Hartmann, Constanze; Triller, Annika; Spehr, Marc; Dittrich, Ralf; Hatt, Hanns; Büttner, Andrea (ChemPlusChem, 2013)
Human sperm chemotaxis to follicular fluid has been well established, but the molecular mechanism(s) for this phenomenon are still largely unclear. Studies indicate that odorant receptors expressed on spermatozoa could play a role in this scenario. It has recently been shown that several synthetic floral scents activate the receptors OR1D2, OR4D1, and OR7A5 in vitro and evoke distinct sperm motility patterns in vivo. However, all agonists found so far are of synthetic origin and, thus, the presence of endogenous structural analogues in female bodily fluids is subject to speculation. Therefore, the aim of the study reported herein was to investigate the occurrence of odor compounds in vaginal secretions and follicular fluid by using gas chromatography-olfactometry. Chemically identified constituents of either bodily fluid were then analyzed for activation of recombinant chemoreceptors and candidate ligands were further tested for induction of sperm Ca2+ signals. Through using this approach, two novel odorant receptor-ligand pairs are reported and human sperm Ca2+ elevations in response to both odorous substances, namely 5α-androst-16-en-3-one and 4-hydroxy-2,5-dimethyl-3(2H)-furanone, are shown.<br

Sperm activating odorous substances in human follicular fluid and vaginal secretion: Identification by gas-chromatography-olfactometry and CA2+-imaging - Hartmann, Constanze; Triller, Annika; Spehr, Marc; Dittrich, Ralf; Hatt, Hanns; Büttner, Andrea (ChemPlusChem, 2013)
Human sperm chemotaxis to follicular fluid has been well established, but the molecular mechanism(s) for this phenomenon are still largely unclear. Studies indicate that odorant receptors expressed on spermatozoa could play a role in this scenario. It has recently been shown that several synthetic floral scents activate the receptors OR1D2, OR4D1, and OR7A5 in vitro and evoke distinct sperm motility patterns in vivo. However, all agonists found so far are of synthetic origin and, thus, the presence of endogenous structural analogues in female bodily fluids is subject to speculation. Therefore, the aim of the study reported herein was to investigate the occurrence of odor compounds in vaginal secretions and follicular fluid by using gas chromatography- olfactometry. Chemically identified constituents of either bodily fluid were then analyzed for activation of recombinant chemoreceptors and candidate ligands were further tested for induction of sperm Ca2+ signals. Through using this approach, two novel odorant receptor-ligand pairs are reported and human sperm Ca2+ elevations in response to both odorous substances, namely 5α-androst-16-en-3-one and 4-hydroxy-2,5-dimethyl-3(2H)-furanone, are shown. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
UnivIS-Import:2015-04-14:Pub.2013.nat.dchph.llmch.sperma
Keywords: biological activity; calcium signaling; gas chromatography-olfactometry; membrane proteins; receptors

Spontaneous antral follicle formation and metaphase II oocyte from a non-stimulated prepubertal ovarian tissue xenotransplant - Lotz, Laura; Liebenthron, Jana; Nichols-Burns, Stephanie M.; Montag, Markus; Hoffmann, Inge; Beckmann, Matthias; Van Der Ven, Hans; Toepfer, Dagmar; Dittrich, Ralf (Reproductive Biology and Endocrinology, 2014)
Current strategies in cancer treatment have markedly increased the rates of remission and survival for cancer patients, but are often associated with subsequent sterility. While there are various options available to an adult female depending on the patient's particular situation, the only realistic option for preserving fertility in prepubertal females is to cryopreserve ovarian tissue. This is the first report of a morphologically mature oocyte collected from non-stimulated prepubertal ovarian tissue xenotransplants.Ovarian tissue from a 6 year old patient suffering from nephroblastoma was removed and cryopreserved for fertility preservation. The frozen-thawed ovarian tissue fragments were xenotransplanted to bilaterally oophorectomized severe combined immunodeficiency (SCID) mice to assess follicle development.Antral follicle formation occurred post-xenotransplantation in a single ovarian fragment without exogenous hormone stimulation. A morphologically maturing oocyte was harvested from these follicles.Prepubertal human ovarian follicles and oocytes can be matured after xenotransplantation even without exogenous hormone stimulation. These results indicate that tissue collected from prepubertal patients can support fertility in cancer survivors.
EVALuna2:17456

Stammzellen aus Nabelschnurblut - ein besonderes Gut: Informationen für eine fachärztliche Beratung der Schwangeren - Goecke, Tamme W.; Jud, Sebastian; Weisbach, Volker Günter; Bender, A. W.; Schneider, Holm (Geburtshilfe und Frauenheilkunde, 2010)
CRIS-Team Scopus Importer:2020-07-01

Standard changing news der Senologie und der Gynäkologischen Onkologie 2018 - Preu, Caroline; Heindl, Felix; Jud, Sebastian; Hein, Alexander; Hack, Carolin; Beckmann, Matthias; Lux, Michael P.; Rauh, Claudia (Klinikarzt, 2018)
CRIS-Team Scopus Importer:2021-07-19

Standard changing news der Senologie und der Gynäkologischen Onkologie 2019: Neue Arzneimittelzulassungen und Änderungen bestehender Therapiekonzepte - Preuβ, Caroline; Hein, Alexander; Beckmann, Matthias; Jud, Sebastian (Klinikarzt, 2019)
CRIS-Team Scopus Importer:2020-02-21

Standard Changing News der Senologie und der Gynäkologischen Onkologie 2020 - Preuβ, Caroline; Hein, Alexander; Beckmann, Matthias; Jud, Sebastian (Klinikarzt, 2020)
CRIS-Team Scopus Importer:2020-12-11

Standard Changing News der Senologie und Gynäkologischen Onkologie - Rauh, Claudia; Jud, Sebastian; Hein, Alexander; Hack, Carolin; Fasching, Peter; Beckmann, Matthias; Lux, Michael P. (Klinikarzt, 2017)
CRIS-Team Scopus Importer:2021-07-19

Standardized evaluation of tumor-infiltrating lymphocytes in breast cancer: results of the ring studies of the international immuno-oncology biomarker working group - Denkert, Carsten; Wienert, Stephan; Poterie, Audrey; Loibl, Sibylle; Budczies, Jan; Badve, Sunil; Bago-Horvath, Zsuzsanna; Bane, Anita; Bedri, Shahinaz; Brock, Jane; Chmielik, Ewa; Christgen, Matthias; et al. (Modern Pathology, 2016)
Multiple independent studies have shown that tumor-infiltrating lymphocytes (TIL) are prognostic in breast cancer with potential relevance for response to immune-checkpoint inhibitor therapy. Although many groups are currently evaluating TIL, there is no standardized system for diagnostic applications. This study reports the results of two ring studies investigating TIL conducted by the International Working Group on Immuno-oncology Biomarkers. The study aim was to determine the intraclass correlation coefficient (ICC) for evaluation of TIL by different pathologists. A total of 120 slides were evaluated by a large group of pathologists with a web-based system in ring study 1 and a more advanced software-system in ring study 2 that included an integrated feedback with standardized reference images. The predefined aim for successful ring studies 1 and 2 was an ICC above 0.7 (lower limit of 95% confidence interval (CI)). In ring study 1 the prespecified endpoint was not reached (ICC: 0.70; 95% CI: 0.62-0.78). On the basis of an analysis of sources of variation, we developed a more advanced digital image evaluation system for ring study 2, which improved the ICC to 0.89 (95% CI: 0.85-0.92). The Fleiss' kappa value for <60 vs ≥60% TIL improved from 0.45 (ring study 1) to 0.63 in RS2 and the mean concordance improved from 88 to 92%. This large international standardization project shows that reproducible evaluation of TIL is feasible in breast cancer. This opens the way for standardized reporting of tumor immunological parameters in clinical studies and diagnostic practice. The software-guided image evaluation approach used in ring study 2 may be of value as a tool for evaluation of TIL in clinical trials and diagnostic practice. The experience gained from this approach might be applicable to the standardization of other diagnostic parameters in histopathology.
EVALuna2:33063

Standardized Procedures for Patients with Dysplasia and Other Diseases of the Cervix, Vulva, and Vagina at a Certified Dysplasia Unit Prior to the Introduction of the Organized Cervical Cancer Screening Program. - Schulmeyer, Carla; Koch, Martin C.; Dietl, Anna; Stübs, Frederik; Behrens, Annika; Renner, Simone K.; Mehlhorn, Grit; Geppert, Carol-Immanuel; Hartmann, Arndt; Beckmann, Matthias; Gaß, Paul (Geburtshilfe und Frauenheilkunde, 2023)
Introduction Gynecologic dysplasia units and dysplasia consultations are obliged to offer diagnosis and treatment in accordance with the guidelines. The organization of the consultation process, management of patient appointments, diagnosis, and treatment algorithms are heterogeneous. The legislation arising from the new Federal Joint Committee decision, dated 22 November 2018, concerning the organized cervical cancer screening program has been in force since 1 January 2020. In this article we provide an overview of the existing structures and interdisciplinary cooperation of specialized dysplasia units incorporated in certified gynecologic cancer center. Materials and Methods We carried out a retrospective database search of data collected prospectively from 1 July 2014 to 31 December 2019 at the dysplasia unit at the Department of Gynecology and Obstetrics, Erlangen University Hospital, which was the first dysplasia unit to be certified in 2014. Results A total of 5594 patients presented at the unit, and 16061 colposcopic, vulvoscopic, and anoscopic examinations were performed. Approximately 4100 examinations of the cervix, vagina, vulva, and anus are carried out each year, 1600 of these were exclusively cervix colposcopies. A total of 12197 cytology results were assessed, as well as 4850 histology results, and 8193 high-risk HPV tests. The quality indicators required by the dysplasia unit for annual recertification were met each year. Conclusion Certified dysplasia units and consultations form the central component in the algorithm for further investigating abnormal screening results; but they are also the first point of contact for a large number of patients with acute or chronic complaints in the genital region.
EVALuna2:542837

Standards Used by a Clinical and Scientific Endometriosis Center for the Diagnosis and Therapy of Patients with Endometriosis - Burghaus, Stefanie; Hildebrandt, Thomas; Fahlbusch, Christine; Heusinger, Katharina; Antoniadis, Sophia; Lermann, Johannes; Hackl, Janina; Häberle, Lothar; Renner, Stefan P.; Fasching, Peter; Beckmann, Matthias; Blum, Simon (Geburtshilfe und Frauenheilkunde, 2019)
Endometriosis is one of the most common benign gynecological diseases. The extremely heterogeneous complex of symptoms complicates the diagnosis and treatment of this disease. In most patients, there is a latency period of several years between the first occurrence of symptoms and the definitive diagnosis. This paper aims (1) to evaluate standards for the diagnosis and treatment of patients with (symptoms suspicious for) endometriosis in terms of feasibility, and (2) to assess the potential use of data collected by a certified clinical and scientific endometriosis center to answer scientific questions. Standards for outpatient consultations were developed for a special endometriosis outpatient clinic. Between January 2014 and December 2017, a total of 1715 outpatients with a suspicion of endometriosis presented to this special endometriosis outpatient clinic; the diagnosis and treatment of patients was carried out in accordance with the developed standards. Data of this patient cohort obtained from patient records created during outpatient consultations and from a questionnaire recorded in an Oracle-based database was analyzed. The patient cohort was also compared with another patient cohort who had attended different outpatient clinics and had been diagnosed intraoperatively with endometriosis. 41.8% of patients examined during special outpatient consultations had surgery for suspicion or recurrence of endometriosis. Endometriosis was confirmed in 81.5% of cases. Pain symptoms were the main indication for surgery in 70.1% of cases compared to 45.1% of cases in the comparison group. The structured approach used in the special endometriosis outpatient clinic is a key aspect of the care provided by the certified clinical and scientific endometriosis center. It ensures that patients are diagnosed and treated in accordance with guideline recommendations, that diagnosis and treatment comply with certification requirements, and that the collected data can be used to answer scientific questions.
CRIS-Team Scopus Importer:2019-06-04
Keywords: diagnostic; endometriosis; lower abdominal pain; sterility

Statement by the German Society for Gynecology and Obstetrics e.V. on the Topic - More Knowledge "Breast Density" - Seelbach-Goebel, Birgit; Beckmann, Matthias (Geburtshilfe und Frauenheilkunde, 2017)
EVALuna2:36148

Statement of the AGO and AG-CPC on the Aftercare/Follow-up for Surgical Procedures of the Lower Genital Tract after the Introduction of a New Cancer Screening Guideline - Hillemanns, Peter; Tempfer, Clemens; Beckmann, Matthias; Kueppers, Volkmar; Quaas, Jens (Geburtshilfe und Frauenheilkunde, 2020)
The new guideline on organized cancer screening programs has been in force in Germany since January 1st, 2020. The guideline has amended earlier recommendations on cytological examinations, which were previously carried out annually during screening. The guidelines-based recommendations on the appropriate follow-up for preinvasive and invasive lesions of the uterine cervix and endometrium are briefly outlined and differentiated from screening cytology and Pap/HPV co-testing as described in the guideline on organized cancer screening programs (oKFE-RL).
CRIS-Team WoS Importer:2020-09-11

Statement of the Uterus Commission of the Gynecological Oncology Working Group (AGO) on Neoadjuvant Chemotherapy Prior to Definitive Radiochemotherapy in Patients with Locally Advanced Cervical Cancer - Tempfer, Clemens; Fehm, Tanja; Vordermark, Dirk; Marnitz-Schulze, Simone; Beckmann, Matthias; Denschlag, Dominik; Brucker, Sara; Wallwiener, Markus; Eichbaum, Michael; Ataseven, Beyhan; Hillemanns, Peter (Geburtshilfe und Frauenheilkunde, 2024)
The presentation of the results of the prospective randomized international multicenter GCIG INTERLACE trial at the 2023 congress of the European Society of Medical Oncology (ESMO) is likely to change the therapy for locally advanced cervical cancer. In the GCIG INTERLACE trial, six cycles of neoadjuvant chemotherapy administered weekly and consisting of carboplatin AUC2 and paclitaxel 80 mg/m 2followed by definitive radiochemotherapy with pelvic radiotherapy (40-50.4 Gray) and cisplatin (40 mg/m 2once a week for 5 weeks) and brachytherapy (total dose EQD2 at least 78 Gy at point A) (experimental arm) were compared with definitive radiochemotherapy alone (standard arm) in patients with locally advanced cervical cancer (Fédération Internationale de Gynécologie et d Obstétrique [FIGO] 2008 stage IB1/node positive, IB2, II, IIIB and IVA) and was found to be significantly superior with significantly longer recurrence-free survival (hazard ratio [HR] 0.65; 95% confidence interval [CI] 0.64-0.91; p = 0.013) and significantly longer overall survival rates (HR 0.61; 95% CI: 0.40-0.91; p = 0.04) after 5 years follow-up. After considering the results of the GCIG INTERLACE trial published at the congress, the Uterus Commission of the AGO is of the opinion that neoadjuvant chemotherapy with carboplatin AUC2 and paclitaxel 80 mg/m 2d1, q7, x6 may be offered to patients with locally advanced cervical cancer (FIGO stage IB1/node positive, IB2, II, IIIB and IVA) in addition to the current standard therapy after the patient has been informed about the risks, with the decision taken on a case-by-case basis. However, before this approach can be discussed at guideline level or defined as the new therapy standard, it will be necessary to wait until the data from the full publication are available.
CRIS-Team Scopus Importer:2024-04-26
Keywords: cervical cancer; locally advanced disease; neoadjuvant chemotherapy; radical hysterectomy

Statement of the Uterus Commission of the Gynecological Oncology Working Group (AGO) on Surgical Therapy for Patients with Stage IA2-IIB1 Cervical Cancer - Fehm, Tanja; Beckmann, Matthias; Mahner, Sven; Denschlag, Dominik; Brucker, Sara; Hillemanns, Peter; Tempfer, Clemens (Geburtshilfe und Frauenheilkunde, 2023)
The presentation of the results of the prospective randomized international multicenter study AGO-OP.8 - CCTG CX.5 - SHAPE at the annual conference of the American Society of Clinical Oncology (ASCO) in 2023 will affect the surgical treatment of early-stage cervical cancer. In the SHAPE study, simple total hysterectomy (experimental arm) was found to be non-inferior to radical hysterectomy (standard arm) to treat patients with early-stage cervical cancer (FIGO stages [2018] IA2 - IB1 ≤ 2 cm with an infiltration depth of < 1 cm); after 3 years' follow-up the pelvic recurrence rate was 2.52% (experimental arm) compared to 2.17% (standard arm) with no statistically significant difference with regards to recurrence-free survival and overall survival rates. After weighing up the results of the SHAPE study published at the conference, the Uterus Organ Commission of AGO is of the opinion that, in addition to the use of radical hysterectomy to treat patients with invasive cervical cancer which is FIGO stage IA2 - IB1 ≤ 2 cm with an infiltration depth of < 1 cm, simple total hysterectomy may also be considered for primary surgical therapy on a case-by-case basis after suitable explanation of the associated risks. It will be necessary to wait for the data of the full publication before discussing whether this approach should be included in official guidelines and defining it as a new therapy standard.
CRIS-Team Scopus Importer:2023-10-27
Keywords: cervical cancer; early-stage; radical hysterectomy; simple hysterectomy

State-of-the-Art Treatment and Novel Agents in Local and Distant Recurrences of Cervical Cancer - Tempfer, Clemens B.; Beckmann, Matthias (Oncology Research and Treatment, 2016)
Depending on the stage at initial presentation, cervical cancer will recur in 25-61% of women. Typical manifestations of recurrent cervical cancer include the central pelvis and the pelvic side walls as well as retroperitoneal lymph node basins in the pelvis and the para-aortic region, and - more rarely - supraclavicular lymph nodes. There are no typical symptoms of recurrent cervical cancer. Women with suspected recurrence after cervical cancer based on gynecological examination or organ-specific symptoms must undergo imaging studies and - if technically feasible - biopsy with histological verification, especially in cases of distant metastases, in order to rule out a second primary. Radiotherapy-naïve women should be treated with salvage radiochemotherapy with curative intention. For women with previous radiotherapy, surgery in the form of hysterectomy, local resection, or pelvic exenteration is the treatment of choice. Pelvic exenteration can lead to cure in selected patients, but at the price of a high rate of complications and significant morbidity and mortality. If complete surgical resection is not feasible or if the woman is not a candidate for surgery, chemotherapy with palliative intent should be offered. Patients with recurrent disease outside the pelvis are candidates for systemic chemotherapy. Several agents have shown to be active in this situation, either in single-agent or combination regimens. Platinum-containing regimens have a superior efficacy over non-platinum regimens and bevacizumab may be added to chemotherapy.
EVALuna2:32962

Status quo and future directions of digitalization in gynecology and obstetrics in Germany: a survey of the commission Digital Medicine of the German Society for Gynecology and Obstetrics - Pfob, André; Hillen, Christoph; Seitz, Katharina; Griewing, Sebastian; Becker, Sven; Bayer, Christian; Wagner, Uwe; Fasching, Peter; Wallwiener, Markus (Archives of Gynecology and Obstetrics, 2024)
Purpose: Digitalization plays a critical role and is beginning to impact every part of the patient journey, from drug discovery and data collection to treatment and patient-reported outcomes. We aimed to evaluate the status quo and future directions of digital medicine 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, telemedicine, digital health applications (DIGAs), and future expectations. Results: In all, 91 participants completed the survey. Median age was 34 years; 67.4% (60 of 89) were female and 32.6% (29 of 89) were male. About 10% (9 of 88) have prescribed DIGAs to date and 14% (12 of 86) offer telemedical appointments. Among those who do not use digital medicine, very few plan to do so in the near future. Reasons include missing software interfaces, lack of time to try out new things, lack of knowledge, lack of monetary compensation (66.3%), and employee concerns. A majority agreed that digitalization will help to save time and improve patient care and that intelligent algorithms will aid clinicians in providing patient care to women. Conclusions: The status quo and future directions of digital medicine in gynecology and obstetrics in Germany are characterized by contradicting expectations regarding the benefits of digital medicine and its actual implementation in clinical routine. This represents an important call to action to meet the requirements of modern patient care.
CRIS-Team Scopus Importer:2023-12-08
Keywords: Artificial intelligence; Digital health; eHealth; Gynecology and obstetrics; Implementation

Stellenwert der Vakzine gegen humane Papillomaviren in der Prävention von Krebserkrankungen - Schulmeyer, Carla; Knöll, Antje; Iro, Heinrich; Müller, Susanna; Beckmann, Matthias (Onkologe, 2021)
Background: Human papillomaviruses (HPV) are the most common causes of genital viral infections. HPV infections usually heal, but can also persist and thus cause lesions of different grades. Infections with high-risk HPV types (hrHPV) 16, 18, 31, 33, 45, 52, and 58 are responsible for causing 90% of cervical cancer cases in Europe. Head and neck cancer, vaginal and vulvar cancer and their precursors, as well as penile or anal cancer may also be associated with hrHPV. Objectives: The aim of this work is to demonstrate the importance of HPV vaccines in the prevention of genital as well as head and neck cancers. Materials and methods: This work is based on a selective literature search in the PubMed database on the correlation between HPV vaccines and HPV-associated cancer. Results: HPV vaccination ensures a high level of protection against precancerous lesions and cancer of the cervix, vagina, vulva, anus, and genital warts. Conclusions: Results of HPV vaccination and its positive effects on head and neck tumors is expected within the next few decades.
CRIS-Team Scopus Importer:2021-11-05
Keywords: Condylomata acuminata; HPV; Oropharyngeal neoplasms; Sexually transmitted diseases; Uterine cervical neoplasms

Stellungnahme des Präsidenten und des Leitlinien-Beauftragten der DGGG - Absence of Evidence Is Not Evidence of Absence - Carl Edward Sagan (911.1934-20.12.1996, US-amerikanischer Astronom, Astrophysiker, Exobiologe) - Scharl, Anton; Beckmann, Matthias (Geburtshilfe und Frauenheilkunde, 2021)
CRIS-Team Scopus Importer:2021-08-27

Strong hypoxia reduces leptin synthesis in purified primary human trophoblasts - Nuesken, E.; Herrmann, Y.; Wohlfarth, M.; Goecke, Tamme W.; Appel, S.; Schneider, Holm; Doetsch, J.; Nuesken, K. D. (Placenta, 2015)
Introduction Oxygen availability severely affects placental function. During placental hypoxia, stabilization of hypoxia inducible factors (HIFs) affects transcription, and leptin gene expression concomitantly increases in vivo and in vitro. However, a causal relationship is uncertain.
CRIS-Team Scopus Importer:2020-07-01
Keywords: Hypoxia; Leptin/leptin receptor; Placenta; Trophoblast

STUDY OF TELOMERE LENGTH AND DIFFERENT MARKERS OF OXIDATIVE STRESS IN PATIENTS WITH PARKINSON'S DISEASE - Watfa, Ghassan; Dragonas, C.; Brosche, Thorolf; Dittrich, Ralf; Sieber, Cornel; Alecu, C.; Benetos, A.; Nzietchueng, R. (Journal of Nutrition, Health & Aging, 2011)
Background: Many studies have shown that short telomere length (TL) is associated with high oxidative stress and various age-related diseases. Parkinson's disease (PD) is an age-related disease, and although its pathogenic mechanism is uncertain, oxidative stress is believed to be implicated in this pathology. The aim of this case-control study was to assess both TL and the different markers of oxidative stress in elderly patients with PD compared to age control subjects. Methods: 20 PD patients and 15 age-matched controls, >65 years were studied. TL was measured by Southern blotting from DNA samples extracted from white blood cells. Superoxide dismutase (SOD) activity and plasma levels of total glutathione and protein carbonyls were determined. Results: There was a trend for lower TL in PD patients: 6.06 +/- 0.81 kb in PD versus 6.45 +/- 0.73 kb in controls (p = 0.08). No significant difference was found between the two groups in terms of oxidative stress markers. In controls, age was the main determinant of telomere shortening (r = -0.547; p = 0.03) whereas, in PD patients, telomere shortening was mainly dependent on plasmatic concentrations of carbonyl proteins (r= -0.544; p=0.044). In PD patients, a negative association was observed between plasma carbonyl protein levels and SOD activity (r= -0.622, p=0.004). Conclusions: In PD, TL is shorter in presence of high oxidative stress as measured by carbonyl protein levels. The absence of telomere attrition with age among patients with PD could reflect a telomere regulation by mechanisms other than age.
Keywords: Aging; Parkinson's disease; oxidative stress; telomere length

Style-Extracting Diffusion Models for Semi-supervised Histopathology Segmentation - Öttl, Mathias; Wilm, Frauke; Steenpaß, Jana; Qiu, Jingna; Rübner, Matthias; Hartmann, Arndt; Beckmann, Matthias; Fasching, Peter; Maier, Andreas; Erber, Ramona; Kainz, Bernhard; Breininger, Katharina (Lecture Notes in Computer Science (including subseries Lecture Notes in Artificial Intelligence and Lecture Notes in Bioinformatics), 2025)
Deep learning-based image generation has seen significant advancements with diffusion models, notably improving the quality of generated images. Despite these developments, generating images with unseen characteristics beneficial for downstream tasks has received limited attention. To bridge this gap, we propose Style-Extracting Diffusion Models, featuring two conditioning mechanisms. Specifically, we utilize 1) a style conditioning mechanism which allows to inject style information of previously unseen images during image generation and 2) a content conditioning which can be targeted to a downstream task, e.g., layout for segmentation. We introduce a trainable style encoder to extract style information from images, and an aggregation block that merges style information from multiple style inputs. This architecture enables the generation of images with unseen styles in a zero-shot manner, by leveraging styles from unseen images, resulting in more diverse generations. In this work, we use the image layout as target condition and first show the capability of our method on a natural image dataset as a proof-of-concept. We further demonstrate its versatility in histopathology, where we combine prior knowledge about tissue composition and unannotated data to create diverse synthetic images with known layouts. This allows us to generate additional synthetic data to train a segmentation network in a semi-supervised fashion. We verify the added value of the generated images by showing improved segmentation results and lower performance variability between patients when synthetic images are included during segmentation training. The code of the method is publicly available at https://github.com/OettlM/STEDM.
Created from Fastlane, Scopus look-up

Superpixel Pre-segmentation of HER2 Slides for Efficient Annotation - Öttl, Mathias; Mönius, Jana; Marzahl, Christian; Rübner, Matthias; Geppert, Carol-Immanuel; Hartmann, Arndt; Beckmann, Matthias; Fasching, Peter; Maier, Andreas; Erber, Ramona; Breininger, Katharina (Informatik aktuell, 2022)
Supervised deep learning has shown state-of-the-art performance for medical image segmentation across different applications, including histopathology and cancer research; however, the manual annotation of such data is extremely laborious. In this work, we explore the use of superpixel approaches to compute a pre-segmentation of HER2 stained images for breast cancer diagnosis that facilitates faster manual annotation and correction in a second step. Four methods are compared: standard simple linear iterative clustering (SLIC) as a baseline, a domain adapted SLIC, and superpixels based on feature embeddings of a pretrained ResNet-50 and a denoising autoencoder. To tackle oversegmentation, we propose to hierarchically merge superpixels, based on their content in the respective feature space. When evaluating the approaches on fully manually annotated images, we observe that the autoencoder-based superpixels achieve a 23% increase in boundary F1 score compared to the baseline SLIC superpixels. Furthermore, the boundary F1 score increases by 73% when hierarchical clustering is applied on the adapted SLIC and the autoencoder-based superpixels. These evaluations show encouraging first results for a pre-segmentation for efficient manual refinement without the need for an initial set of annotated training data.<br
CRIS-Team Scopus Importer:2022-05-06

Supportive Infusions in Integrative Breast and Gynecological Oncology - Report on Patients' Satisfaction and Self-reported Effects and Side Effects - Hack, Carolin; Antoniadis, Sophia; Beckmann, Matthias; Brandl, Anna; Fasching, Peter; Hackl, Janina; Langemann, Hanna; Stock, Katja; Weber, Natalie; Theuser, Anna-Katharin (Geburtshilfe und Frauenheilkunde, 2018)
Background During cancer therapy, many patients suffer from malnutrition or vitamin deficiency. Treatment for nutrition-related deficiencies should therefore include nutritional therapy and possibly oral or intravenous substitution of micronutrients. Little information exists on multinutrient infusion therapies. The aim of this study was to develop standardized infusion protocols for integrative medicine infusions with micronutrients (IMed infusions) and to report on side effects of the treatment and patients' satisfaction with it. Methods For the IMed consultancy service, four special formulas for intravenous use were developed in cooperation with the pharmacy at Erlangen University Hospital. A retrospective cross-sectional study was conducted between October 2015 and January 2018 in which 45 patients with gynecological or breast cancer (BC) and IMed infusion therapy were included. Follow-up data were obtained from 20 patients using a standardized questionnaire on IMed infusions. Results A total of 280 IMed infusions were administered in the study period. The majority of the patients received an IMed regeneration infusion (78%). The majority of the patients had BC and were receiving chemotherapy. Most patients reported a high or very high level of satisfaction with the organization (60%), general treatment (65%) and counseling (85%). Subjective improvement in their disease-related and therapy-induced symptoms, such as fatigue, polyneuropathy and physical efficiency, was reported by 70% of the patients, while 75% reported a subjective increase in quality of life. Side effects were rare and minor. Conclusions Therapy with IMed infusions in women with BC or gynecological cancer requires the same standards set for drug therapy. Although vitamins represent dietary supplements, appropriate assessment of the patient's medical history is needed and patients must receive appropriate information. For this purpose, standardized processes, as in the context of an IMed consultancy service, are helpful.
EVALuna2:209954

Surgical Aspects of Ovarian Tissue Removal and Ovarian Tissue Transplantation for Fertility Preservation - Beckmann, Matthias; Dittrich, Ralf; Findeklee, S.; Lotz, Laura (Geburtshilfe und Frauenheilkunde, 2016)
Introduction: The removal of ovarian tissue prior to starting oncologic treatment and the subsequent transplantation of this tissue after completing therapy have become increasingly important surgical fertility-preserving techniques. The aim of this review was to investigate the different surgical techniques used for this method reported in the literature to date and to discuss the advantages and disadvantages of the respective techniques.Review:A search was done in MEDLINE using a defined algorithm to find studies published between January 2004 and December 2015. All study designs were included in our review if they contained statements on the surgical technique used. We found 16 publications (8 retrospective cohort studies, 6 case reports and 2 systematic reviews) with a total of 1898 female patients which reported on the surgical technique used for ovarian biopsy and 15 publications (7 retrospective cohort studies, 6 case reports and 2 systematic reviews) with a total of 455 women which mentioned the surgical technique used for ovarian transplantation. Different surgical techniques can be used both for ovarian biopsy and for the transplantation of ovarian tissue. A number of different surgical routes have been used, and the amount of tissue extracted, the instruments used, the treatment of the ovary, the transplantation site, the blood supply to the transplanted ovarian tissue and the procedure used for simultaneous surgical interventions vary.Conclusion:In future, one of the tasks will be to establish a standard surgical method for ovarian extraction and transplantation which will have a low rate of complications and a high pregnancy and birth rate while ensuring that the transplanted tissue is fully functional.
EVALuna2:32951

Surgical outcome after neoadjuvant chemotherapy and bevacizumab: results from the GeparQuinto study (GBG 44) - Gerber, Bernd; Von Minckwitz, Gunter; Eidtmann, Holger; Rezai, Mahdi; Fasching, Peter; Tesch, Hans; Eggemann, Holm; Schrader, Iris; Kittel, Kornelia; Hanusch, Claus; Solbach, Christine; Jackisch, Christian; et al. (Annals of Surgical Oncology, 2014)
Bevacizumab, a humanized monoclonal antibody against vascular endothelial growth factor, has shown increased pathological complete response rates when added to neoadjuvant chemotherapy. In various cancer types, bevacizumab treatment was accompanied by an increased risk of bleedings and other surgical complications. We assessed associated surgical complications.In the GeparQuinto trial, 1,948 patients were randomized to receive four cycles epirubicin/cyclophosphamide (EC, 90/600 mg/m(2) q3w) followed by four cycles docetaxel (D, 100 mg/m(2) q3w) each with (ECB-DB) or without (EC-D) bevacizumab (B, 15 mg/kg q3w) concurrent with chemotherapy. Surgery had to be performed not earlier than 28 days after the last bevacizumab infusion, but within days 21 and 35 after the last chemotherapy.In 743 (38.1 %) patients, a surgical complication (bleedings, hematomas, necrosis, wound infections, abscess) was documented prospectively. Baseline characteristics of the patients were well balanced between both arms. The breast-conserving surgery (BCS) rate (N = 502) was 69.1 % (EC-D) and 71.9 % (ECB-DB; p = 0.464). The first surgical procedure was performed at a median of 29 (EC-D) and 34 days (ECB-DB) after last chemotherapy with or without bevacizumab infusion (p < 0.001). Surgical complications were documented in 38 (10.9 %; EC-D) and 59 (15.0 %; ECB-DB) patients (p = 0.103). Surgical complications were significantly higher after ECD-DB only in patients treated with BCS (N = 53; p = 0.029) or in those requiring repeat surgery in order achieve clear margins (N = 23; p = 0.037) compared to the EC-D group.Addition of bevacizumab to neoadjuvant chemotherapy might be associated with an increased risk for surgical complications in patients treated with BCS or after repeated surgeries.
EVALuna2:17510

Surgical treatment of cervical cancer Operative Therapie des Zervixkarzinoms - Fehm, Tanja; Gantert, Daniel; Martignoni, Franca; Koch, Martin; Beckmann, Matthias (Onkologe, 2020)
Background: Surgery represents the first choice for treatment of early cervical carcinoma (FIGO IA1 to FIGO IIa according to Fédération Internationale de Gynécologie et d’Obstétrique). The extent of surgical therapy for the patient should be determined based on the patient’s age and tumor spread, particularly if fertility preservation is desired. More recently, less radical surgical procedures and concepts for sentinel lymph node biopsy are increasingly used in order to reduce mortality and morbidity. Controversy is currently emerging in the context of new studies regarding the choice of surgical approach. Objective: In this article, surgical options for the treatment of cervical cancer are reviewed. Materials and methods: An overview of the current study situation and literature is provided, taking into consideration the current German S3 guideline on cervical carcinoma. Results: Localized cervical cancer (≤FIGO IIA) is primarily treated by surgery. Recent studies, e.g. SHAPE, are investigating whether less radical surgical procedures can provide adequate oncological safety. A fertility-preserving approach is possible up to stage IB1 depending on the presence of risk factors. After the study results of the LACC trial were published with increased recurrence and mortality rate in the group undergoing laparoscopic surgery compared to the laparotomy group, patients must be informed about these data prior to decision making regarding the route of hysterectomy. Conclusion: The treatment of cervical cancer should be conducted according to the stage. Surgery is key in the treatment of early cervical carcinoma. Even less radical procedures seem to provide adequate oncological safety.
CRIS-Team Scopus Importer:2020-04-28
Keywords: Fertility preservation; Hysterectomy; Sentinel lymph node biopsy; Trachelectomy; Uterine cervical neoplasms

Surgical treatment of endometrial cancer - Emons, G.; Brucker, S. Y.; Fleisch, M. C.; Mueller, M.; Juhasz-Boess, E.; Kiesel, L.; Runnebaum, I. B.; Friedrich, M.; Mustea, A.; Erdogan, S.; Beckmann, Matthias (Die Gynäkologie, 2022)
In July 2022, the first update (Version 2.0) of the German S3 guideline on the diagnosis, treatment and follow-up of patients with endometrial cancer was published, supported by the Leitlinienprogramm Onkologie (Oncology Guideline Program). This article is the summary of Chap. 6: "Surgical Treatment". Relevant innovations compared to version 1.0 include the introduction of molecular classification and sentinel node biopsy, as well as the option of neoadjuvant chemotherapy for advanced cases where primary cytoreductive surgery is not possible.
CRIS-Team WoS Importer:2022-07-29

Surprising prenatal toxicity of epidermal lipoxygenase-3 - Vierling, F.; Dick, Angela; Wahlbuhl, Mandy; Krieg, P.; Henke, Christine; Ruebner, M.; Schneider, Holm (Placenta, 2014)
Metabolites of the epidermal lipoxygenase-3 (eLOX-3) are involved in various metabolic pathways. Most unexpectedly, intra-amniotic delivery of eLOX-3 to mice at gestational day 14.5, both via an adenoviral vector and as recombinant protein, resulted in fetal growth restriction and intrauterine death. Periodic acid-Schiff staining and RT-PCR analysis of placentae from fetuses exposed to eLOX-3 indicated a lack of glycogen trophoblasts in the junctional zone. Placenta-specific gene expression was altered. Thus, the observed prenatal toxicity of eLOX-3 could be due to a strong effect on placental development.
EVALuna2:17431

Survival after adding capecitabine and trastuzumab to neoadjuvant anthracycline-taxane-based chemotherapy for primary breast cancer (GBG 40–GeparQuattro) - Von Minckwitz, G.; Rezai, M.; Fasching, Peter; Huober, J.; Tesch, H.; Bauerfeind, I.; Hilfrich, J.; Eidtmann, H.; Gerber, B.; Hanusch, C.; Blohmer, J. U.; Costa, S. D.; et al. (Annals of Oncology, 2014)
The GeparQuattro study showed that adding capecitabine or prolonging the duration of anthracycline-taxane-based neoadjuvant chemotherapy from 24 to 36 weeks did not increase pathological complete response (pCR) rates. Trastuzumab-treated patients with HER2-positive disease showed a higher pCR rate than patients with HER2-negative disease treated with chemotherapy alone. We here present disease-free (DFS) and overall survival (OS) analyses.Patients (n = 1495) with cT >= 3 tumors, or negative hormone-receptor status, or positive hormone-receptor and clinically node-positive disease received four times epirubicin/cyclophosphamide and were thereafter randomly assigned to four times docetaxel (Taxotere), or four times docetaxel/capecitabine over 24 weeks, or four times docetaxel followed by capecitabine over 36 weeks. Patients with HER2-positive tumors received 1 year of trastuzumab, starting with the first chemotherapy cycle. Follow-up was available for a median of 5.4 years.Outcome was not improved for patients receiving capecitabine (HR 0.92; P = 0.463 for DFS and HR 93; P = 0.618 for OS) as well as for patients receiving 36 weeks of chemotherapy (HR 0.97; P = 0.818 for DFS and HR 0.97; P = 0.825 for OS). Trastuzumab-treated patients with HER2-positive disease showed similar DFS (P = 0.305) but a significantly better adjusted OS (P = 0.040) when compared with patients with HER2-negative disease treated with chemotherapy alone. Recorded long-term cardiac toxicity was low.Long-term results, similar to the results of pCR, do not support the use of capecitabine in the neoadjuvant setting in addition to an anthracycline-taxane-based chemotherapy. However, the results support previous data showing a benefit of trastuzumab as predicted by higher pCR rates.
EVALuna2:17517

Survival after neoadjuvant chemotherapy with or without bevacizumab or everolimus for HER2-negative primary breast cancer (GBG 44-GeparQuinto)+ - Von Minckwitz, G.; Loibl, S.; Untch, M.; Eidtmann, H.; Rezai, M.; Fasching, Peter; Tesch, H.; Eggemann, H.; Schrader, I.; Kittel, K.; Hanusch, C.; Huober, J.; et al. (Annals of Oncology, 2014)
The GeparQuinto study showed that adding bevacizumab to 24 weeks of anthracycline-taxane-based neoadjuvant chemotherapy increases pathological complete response (pCR) rates overall and specifically in patients with triple-negative breast cancer (TNBC). No difference in pCR rate was observed for adding everolimus to paclitaxel in nonearly responding patients. Here, we present disease-free (DFS) and overall survival (OS) analyses.Patients (n = 1948) with HER2-negative tumors of a median tumor size of 4 cm were randomly assigned to neoadjuvant treatment with epirubicin/cyclophosphamide followed by docetaxel (EC-T) with or without eight infusions of bevacizumab every 3 weeks before surgery. Patients without clinical response to EC ± Bevacizumab were randomized to 12 weekly cycles paclitaxel with or without everolimus 5 mg/day. To detect a hazard ratio (HR) of 0.75 (? = 0.05, ? = 0.8) 379 events had to be observed in the bevacizumab arms.With a median follow-up of 3.8 years, 3-year DFS was 80.8% and 3-year OS was 89.7%. Outcome was not different for patients receiving bevacizumab (HR 1.03; P = 0.784 for DFS and HR 0.974; P = 0.842 for OS) compared with patients receiving chemotherapy alone. Patients with TNBC similarly showed no improvement in DFS (HR = 0.99; P = 0.941) and OS (HR = 1.02; P = 0.891) when treated with bevacizumab. No other predefined subgroup (HR+/HER2-; locally advanced (cT4 or cN3) or not; cT1-3 or cT4; pCR or not) showed a significant benefit. No difference in DFS (HR 0.997; P = 0.987) and OS (HR 1.11; P = 0.658) was observed for nonearly responding patients receiving paclitaxel with or without everolimus overall as well as in subgroups.Long-term results, in opposite to the results of pCR, do not support the neoadjuvant use of bevacizumab in addition to an anthracycline-taxane-based chemotherapy or everolimus in addition to paclitaxel for nonearly responding patients.NCT 00567554, www.clinicaltrials.gov.
EVALuna2:17516

Survival Analysis After Neoadjuvant Chemotherapy With Trastuzumab or Lapatinib in Patients With Human Epidermal Growth Factor Receptor 2-Positive Breast Cancer in the GeparQuinto (G5) Study (GBG 44) - Untch, Michael; Von Minckwitz, Gunter; Gerber, Bernd; Schem, Christian; Rezai, Mahdi; Fasching, Peter; Tesch, Hans; Eggemann, Holm; Hanusch, Claus; Huober, Jens; Solbach, Christine; Jackisch, Christian; et al. (Journal of Clinical Oncology, 2018)
Purpose The GeparQuinto phase III trial demonstrated a lower pathologic complete response (pCR; pT0 ypN0) rate when lapatinib was added to standard anthracycline-taxane chemotherapy compared with trastuzumab in patients with human epidermal growth factor receptor 2 (HER2) -positive breast cancer. Here, we report the long-term outcomes. Methods Patients with HER2-positive tumors (n = 615) received neoadjuvant treatment with epirubicin (E) plus cyclophosphamide (C), followed by docetaxel (T) in combination with either lapatinib (L) or trastuzumab (H; ECH-TH arm: n = 307; ECL-TL arm: n = 308). All patients received adjuvant trastuzumab for a total of 12 months and 18 months in the ECH-TH and ECL-TL arms, respectively. Median follow-up was 55 months. Results Three-year disease-free survival (DFS), distant DFS (DDFS), and overall survival (OS) were not significantly different between the two treatment arms. Long-term outcomes correlated with pCR (DFS: hazard ratio [HR], 0.63; P = .042; DDFS: HR, 0.55; P = .021; and OS: HR, 0.31; P = .004). A benefit only for OS was observed in patients who were treated with trastuzumab and achieved pCR versus no pCR (HR, 0.15; P = .010), whereas no difference was found in patients with pCR versus without pCR in the lapatinib arm. DFS and DDFS remained unchanged in both treatment arms according to hormone receptor status, whereas OS was significantly better in hormone receptor-positive patients who were treated with neoadjuvant lapatinib (HR, 0.32; P = .019), followed by adjuvant trastuzumab. No difference was observed in hormone receptor-negative patients; however, the small number of events limits this interpretation. Within the hormone receptor-negative cohort, pCR was significantly associated with DFS, DDFS, and OS ( P = .002, .005, and .002, respectively). Conclusion pCR correlated with long-term outcome. In patients with hormone receptor-positive tumors, prolonged anti-HER2 treatment-neoadjuvant lapatinib for 6 months, followed by adjuvant trastuzumab for 12 months-significantly improved survival compared with anti-HER2 treatment with trastuzumab alone.
EVALuna2:56157

Survival analysis of carboplatin added to an anthracycline/taxane-based neoadjuvant chemotherapy and HRD score as predictor of response-final results from GeparSixto - Loibl, S.; Weber, K. E.; Timms, K. M.; Elkin, E. P.; Hahnen, E.; Fasching, Peter; Lederer, Bianca; Denkert, C.; Schneeweiss, A.; Braun, S.; Salat, C. T.; Rezai, M.; et al. (Annals of Oncology, 2018)
Background: In the neoadjuvant GeparSixto study, adding carboplatin to taxane- and anthracycline-based chemotherapy improved pathological complete response (pCR) rates in patients with triple-negative breast cancer (TNBC). Here, we present survival data and the potential prognostic and predictive role of homologous recombination deficiency (HRD). Patients and methods: Patients were randomized to paclitaxel plus nonpegylated liposomal doxorubicin (Myocet®) (PM) or PM plus carboplatin (PMCb). The secondary study end points disease-free survival (DFS) and overall survival (OS) were analyzed. Median follow-up was 47.3 months. HRD was among the exploratory analyses in GeparSixto and was successfully measured in formalin-fixed, paraffin-embedded tumor samples of 193/315 (61.3%) participants with TNBC. Homologous recombination (HR) deficiency was defined as HRD score ≥42 and/or presence of tumor BRCA mutations (tmBRCA). Results: A significantly better DFS (hazard ratio 0.56, 95% CI 0.34-0.93; P = 0.022) was observed in patients with TNBC when treated with PMCb. The improvement of OS with PMCb was not statistically significant. Additional carboplatin did not improve DFS or OS in patients with HER2-positive tumors. HR deficiency was detected in 136 (70.5%) of 193 triple-negative tumors, of which 82 (60.3%) showed high HRD score without tmBRCA. HR deficiency independently predicted pCR (ypT0 ypN0) [odds ratio (OR) 2.60, 95% CI 1.26-5.37, P = 0.008]. Adding carboplatin to PM significantly increased the pCR rate from 33.9% to 63.5% in HR deficient tumors (P = 0.001), but only marginally in HR nondeficient tumors (from 20.0% to 29.6%, P = 0.540; test for interaction P = 0.327). pCR rates with carboplatin were also higher (63.2%) than without carboplatin (31.7%; OR 3.69, 1.46-9.37, P = 0.005) in patients with high HRD score but no tmBRCA. DFS rates were improved with addition of carboplatin, both in HR nondeficient (hazard ratio 0.44, 0.17-1.17, P = 0.086) and HR deficient tumors (hazard ratio 0.49, 0.23-1.04, P = 0.059). Conclusions: The addition of carboplatin to neoadjuvant PM improved DFS significantly in TNBC. Long-term survival analyses support the neoadjuvant use of carboplatin in TNBC. HR deficiency in TNBC and HRD score in non-tmBRCA TNBC are predictors of response. HRD does not predict for carboplatin benefit.
EVALuna2:202797

Survival analysis of the randomised phase III GeparOcto trial comparing neoadjuvant chemotherapy of intense dose-dense epirubicin, paclitaxel, cyclophosphamide versus weekly paclitaxel, liposomal doxorubicin (plus carboplatin in triple-negative breast cancer) for patients with high-risk early breast cancer - Schneeweiss, Andreas; Michel, Laura L.; Möbus, Volker; Tesch, Hans; Klare, Peter; Hahnen, Eric; Denkert, Carsten; Kast, Karin; Pohl-Rescigno, Esther; Hanusch, Claus; Link, Theresa; Untch, Michael; et al. (European Journal of Cancer, 2021)
Background: GeparOcto demonstrated that pathological complete response (pCR) of intense dose-dense epirubicin, paclitaxel and cyclophosphamide (iddEPC) was comparable to weekly paclitaxel/non-pegylated liposomal doxorubicin (plus carboplatin (PM(Cb) in triple-negative breast cancer [TNBC]) in high-risk early breast cancer (BC). Here, we report time-to-event secondary end-points. Patients and methods: Patients were randomised to receive 18 weeks of E (150 mg/m2) followed by P (225 mg/m2) followed by C (2000 mg/m2), each q2w or weekly P (80 mg/m2) plus M (20 mg/m2) plus, in TNBC, Cb (AUC 1.5). Patients with human epidermal growth factor receptor 2-positive (HER2+)BC received trastuzumab (6[loading dose 8]mg/kg q3w) and pertuzumab (420[840]mg q3w) with P and C cycles. Results: 945 patients started treatment (iddEPC n = 470; PM(Cb) n = 475). After a median follow-up of 47.0 (range 1.6–61.5) months, 162 (75 in iddEPC; 87 in PM(Cb)) invasive disease-free survival (iDFS) events and 79 (41 in iddEPC; 38 in PM(Cb)) deaths were reported. No significant difference was observed in 4-year iDFS (81.9% iddEPC versus 79.7% PM(Cb), HR = 1.16 [95%CI 0.85–1.59], log-rank p = 0.334) or 4-year overall survival (OS) (90.3% iddEPC versus 90.6% PM(Cb), HR = 0.90 [95%CI 0.58–1.40], log-rank p = 0.637) overall and in HER2+ and TNBC subgroups. HR+/HER2- BC patients, however, had significantly better 4-year iDFS (77.9% iddEPC versus 62.5% PM, HR = 2.11 [95%CI 1.08–4.10], log-rank p = 0.025) and 4-year OS with iddEPC (94.7% iddEPC versus 80.1% PM, HR = 3.26 [95%CI 1.06–10.00], log-rank p = 0.029). Conclusion: While there was no difference in survival for the entire cohort, the HR+/HER2-subgroup significantly benefits from iddEPC. This supports the concept of an additional effect of NACT beyond pCR in patients with HR+/HER2- BC. ClinicalTrials.gov identifier: NCT02125344.
CRIS-Team Scopus Importer:2021-11-26
Keywords: Breast cancer; Dose-dense; Neoadjuvant chemotherapy; Survival

Survival analysis of the randomized phase III GeparOcto trial comparing neoadjuvant chemotherapy (NACT) of iddEPC versus weekly paclitaxel, liposomal doxorubicin (plus carboplatin in triplenegative breast cancer, TNBC) (PM(Cb)) for patients (pts) with highrisk early breast cancer (BC) - Schneeweiss, A.; Moebus, V.; Tesch, H.; Klare, P.; Denkert, C.; Kast, K.; Hanusch, C.; Link, T.; Untch, M.; Jackisch, C.; Blohmer, J-U.; Fasching, Peter; et al. (ANNALS OF ONCOLOGY, 2020)
CRIS-Team WoS Importer:2020-10-30

Survival and hormone production of isolated mouse follicles in three-dimensional artificial scaffolds after stimulation with bpV(HOpic) - Keckstein, Philip; Dittrich, Ralf; Bleisinger, Nathalie; Hoffmann, Inge; Beckmann, Matthias; Gebhardt, Albrecht; Schmid, Benjamin; Keckstein, Simon (Archives of Gynecology and Obstetrics, 2024)
Purpose: To preserve fertility before gonadotoxic therapy, ovarian tissue can be removed, cryopreserved, and transplanted back again after treatment. An alternative is the artificial ovary, in which the ovarian follicles are extracted from the tissue, which reduces the risk of reimplantation of potentially remaining malignant cells. The PTEN inhibitor bpV(HOpic) has been shown to activate human, bovine and alpacas ovarian follicles, and it is therefore considered a promising substance for developing the artificial ovary. The purpose of this study was to examine the impact of different scaffolds and the vanadate derivative bpV(HOpic) on mice follicle survival and hormone secretion over 10 days. Methods: A comparative analysis was performed, studying the survival rates (SR) of isolated mice follicle in four different groups that differed either in the scaffold (polycaprolactone scaffold versus polyethylene terephthalate membrane) or in the medium—bpV(HOpic) versus control medium. The observation period of the follicles was 10 days. On days 2, 6, and 10, the viability and morphology of the follicles were checked using fluorescence or confocal microscopy. Furthermore, hormone levels of estrogen (pmol/L) and progesterone (nmol/L) were determined. Results: When comparing the SR of follicles among the four groups, it was observed that on day 6, the study groups utilizing the polycaprolactone scaffold with bpV(HOpic) in the medium (SR: 0.48 ± 0.18; p = 0.004) or functionalized in the scaffold (SR: 0.50 ± 0.20; p = 0.003) exhibited significantly higher survival rates compared to the group using only the polyethylene terephthalate membrane (SR: 0). On day 10, a significantly higher survival rate was only noted when comparing the polycaprolactone scaffold with bpV(HOpic) in the medium to the polyethylene terephthalate membrane group (SR: 0.38 ± 0.20 versus 0; p = 0.007). Higher levels of progesterone were only significantly associated with better survival rates in the group with the polycaprolactone scaffold functionalized with bpV(HOpic) (p = 0.017). Conclusion: This study demonstrates that three-dimensional polycaprolactone scaffolds improve the survival rates of isolated mice follicles in comparison with a conventional polyethylene terephthalate membrane. The survival rates slightly improve with added bpV(HOpic). Furthermore, higher rates of progesterone were also partly associated with improved survival.
CRIS-Team Scopus Importer:2024-03-22
Keywords: Artificial ovary; bpV(HOpic); Ovarian follicle

Susceptibility gene mutations in germline and tumors of patients with HER2-negative advanced breast cancer - Fasching, Peter; Hu, Chunling; Hart, Steven N.; Rübner, Matthias; Polley, Eric C.; Gnanaolivu, Rohan D.; Hartkopf, Andreas D.; Hübner, Hanna; Janni, Wolfgang; Hadji, Peyman; Tesch, Hans; Uhrig, Sabrina; et al. (npj Breast Cancer, 2024)
Germline mutations in BRCA1 and BRCA2 (gBRCA1/2) are required for a PARP inhibitor therapy in patients with HER2-negative (HER2−) advanced breast cancer (aBC). However, little is known about the prognostic impact of gBRCA1/2 mutations in aBC patients treated with chemotherapy. This study aimed to investigate the frequencies and prognosis of germline and somatic BRCA1/2 mutations in HER2- aBC patients receiving the first chemotherapy in the advanced setting. Patients receiving their first chemotherapy for HER2- aBC were retrospectively selected from the prospective PRAEGNANT registry (NCT02338167). Genotyping of 26 cancer predisposition genes was performed with germline DNA of 471 patients and somatic tumor DNA of 94 patients. Mutation frequencies, progression-free and overall survival (PFS, OS) according to germline mutation status were assessed. gBRCA1/2 mutations were present in 23 patients (4.9%), and 33 patients (7.0%) had mutations in other cancer risk genes. Patients with a gBRCA1/2 mutation had a better OS compared to non-mutation carriers (HR: 0.38; 95%CI: 0.17–0.86). PFS comparison was not statistically significant. Mutations in other risk genes did not affect prognosis. Two somatic BRCA2 mutations were found in 94 patients without gBRCA1/2 mutations. Most frequently somatic mutated genes were TP53 (44.7%), CDH1 (10.6%) and PTEN (6.4%). In conclusion, aBC patients with gBRCA1/2 mutations had a more favorable prognosis under chemotherapy compared to non-mutation carriers. The mutation frequency of 5% with gBRCA1/2 mutations together with improved outcome indicates that germline genotyping of all metastatic patients for whom a PARP inhibitor therapy is indicated should be considered.
CRIS-Team Scopus Importer:2024-07-19

Systematic Comparison of ECG Delineation Algorithm Performance on Smartwatch Data - Jäger, Katharina; Nissen, Michael; Flaucher, Madeleine; Graf, Luisa; Joanidopoulos, Joana; Anneken, Lars; Hübner, Hanna; Goossens, Chloe; Titzmann, Adriana; Pontones, Constanza; Fasching, Peter; Beckmann, Matthias; et al. (IEEE Access, 2024)
Cardiovascular diseases are the leading cause of global mortality, necessitating early detection and continuous monitoring for timely interventions. Smartwatches with electrocardiogram (ECG) recording capabilities enable real-time, at-home cardiac monitoring. Specific ECG characteristics can provide insights into cardiovascular diseases. The delineation of ECGs, which is the identification of fiducial points (such as onsets, offsets, and peaks), is a time-consuming task. Automated ECG delineation can enhance this process, but existing research comparing available algorithms is limited. Furthermore, to the best of our knowledge, none have addressed single-lead ECGs from smartwatches, which can be noisy and unfiltered. Thus, this study evaluates the best-performing open-source algorithm for single-lead and smartwatch ECG data. We used two public datasets (Lobachevsky University Database, QT Database) and two smartwatch datasets (SmartHeartWatch Dataset, SMART Start Dataset) including two devices (AppleWatch, Withings ScanWatch). Algorithms from three toolkits (NeuroKit, ECGKit, ECGdeli) were assessed based on the time deviation between algorithm outputs and reference annotations, sensitivity, true positives, and false negatives. Results were further evaluated against the Common Standards for Quantitative Electrocardiography (CSE) recommendations. ECGdeli outperformed the other algorithms. For QRS on- and offset, ECGkit shows comparable sensitivity, but otherwise lower scores. NeuroKit consistently shows lower sensitivity across all four data sets, however, the temporal deviation between detected point and reference was higher. Overall, sensitivity scores were higher for Apple Watch data compared to Withings ScanWatch data. This study demonstrates that segmentation algorithms are applicable to single-lead smartwatch ECG data, with ECGdeli being the most stable overall, and NeuroKit recommended for scenarios prioritizing the temporal accuracy of detected points.
CRIS-Team Scopus Importer:2024-11-15
Keywords: Cardiovascular Diseases; ECG Segmentation; Mobile Health; Wearable Devices

Systemic Therapy of Premenopausal Patients with Early Stage Hormone Receptor-Positive, HER2-Negative Breast Cancer - Controversies and Standards in Healthcare - Müller, Volkmar; Fasching, Peter; Nabieva, Naiba; Fehm, Tanja N.; Thill, Marc; Schmidt, Marcus; Kühn, Thorsten; Banys-Paluchowski, Maggie; Belleville, Erik; Juhasz-Böss, Ingolf; Untch, Michael; Kolberg, Hans Christian; et al. (Geburtshilfe und Frauenheilkunde, 2023)
In patients with existing ovarian function, there are some special aspects to adjuvant endocrine therapy in premenopausal patients with hormone receptor-positive, HER2-negative (HR pos./HER2 neg.) breast cancer. Treatment options include tamoxifen with or without a GnRH analog, and aromatase inhibitors with a GnRH analog. Furthermore, ovarian function is affected by previous chemotherapy. Both aromatase inhibitors (+GnRH analogs) and GnRH analogs in combination with tamoxifen are supposed to be indicated for patients at increased risk of recurrence. However, national and international guidelines and therapy recommendations do not provide a clear definition of intermediate or high risk; as a result, therapy decisions are often made for each patient on an individual basis. This is also reflected in the considerable variability at national and international levels, e.g., with regard to the use of aromatase inhibitors + GnRH analogs. This review summarizes the data on completed studies (e.g., SOFT, TEXT, EBCTCG meta-analyses) and the current multigene testing studies (TailorX, RxPonder, ADAPT), discusses the rationale for current studies (e.g., CLEAR-B), and looks ahead to future questions.
CRIS-Team Scopus Importer:2023-06-23
Keywords: aromatase inhibitor; breast cancer; GnRH; premenopausal therapy; tamoxifen

Targeted Intraoperative Radiation Therapy Tumor Bed Boost During Breast-Conserving Surgery After Neoadjuvant Chemotherapy in TNBC and HER2 Positive Breast Cancer - Kolberg, H. C.; Loevey, G.; Akpolat-Basci, L.; Stephanou, M.; Fasching, Peter; Untch, M.; Liedtke, C.; Bulsara, M.; Vaidya, J. S. (2016)
EVALuna2:33059

Targeted Intraoperative Radiotherapy Tumour Bed Boost during Breast-Conserving Surgery after Neoadjuvant Chemotherapy - a Subgroup Analysis of Hormone Receptor-Positive HER2-Negative Breast Cancer - Kolberg, Hans-Christian; Loevey, Gyoergy; Akpolat-Basci, Leyla; Stephanou, Miltiades; Fasching, Peter; Untch, Michael; Hoffmann, Oliver; Bulsara, Max; Vaidya, Jayant S.; Liedtke, Cornelia (Breast Care, 2017)
Introduction: In a previous study our group showed a beneficial effect of targeted intraoperative radiotherapy (TARGIT-IORT) as an intraoperative boost on overall survival after neoadjuvant chemotherapy (NACT) compared to an external boost (EBRT). In this study we present the results of a detailed subgroup analysis of the hormone receptor (HR)-positive HER2-negative patients. Methods: In this cohort study involving 46 patients with HR-positive HER2-negative breast cancer after NACT, we compared the outcomes of 21 patients who received an IORT boost to those of 25 patients treated with an EBRT boost. All patients received whole breast radiotherapy. Results: Median follow-up was 49 months. Whereas disease-free-survival and breast cancer-specific mortality were not significantly different between the groups, the 5-year Kaplan-Meier estimate of overall mortality was significantly lower by 21% with IORT, p = 0.028. Non-breast cancer-specific mortality was significantly lower by 16% with IORT, p = 0.047. Conclusion: Although our results have to be interpreted with caution, we have shown that the improved overall survival demonstrated previously could be reproduced in the HR-positive HER2-negative subgroup. These data give further support to the inclusion of such patients in the TARGIT-B (Boost) randomised trial that is testing whether IORT boost is superior to EBRT boost.
EVALuna2:36209

Targeted intraoperative radiotherapy tumour bed boost during breast-conserving surgery after neoadjuvant chemotherapy - Kolberg, Hans-Christian; Loevey, Gyoergy; Akpolat-Basci, Leyla; Stephanou, Miltiades; Fasching, Peter; Untch, Michael; Liedtke, Cornelia; Bulsara, Max; Vaidya, Jayant S. (Strahlentherapie und Onkologie, 2017)
INTRODUCTION: The use of targeted intraoperative radiotherapy (TARGIT-IORT) as a tumour bed boost during breast-conserving surgery (BCS) for breast cancer has been reported since 1998. We present its use in patients undergoing breast conservation following neoadjuvant therapy (NACT). METHOD: In this retrospective study involving 116 patients after NACT we compared outcomes of 61 patients who received a tumour bed boost with IORT during lumpectomy versus 55 patients treated in the previous 13 months with external (EBRT) boost. All patients received whole breast radiotherapy. Local recurrence-free survival (LRFS), disease-free survival (DFS), distant disease-free survival (DDFS), breast cancer mortality (BCM), non-breast cancer mortality (NBCM) and overall mortality (OS) were compared. RESULTS: Median follow up was 49 months. The differences in LRFS, DFS and BCM were not statistically significant. The 5‑year Kaplan-Meier estimate of OS was significantly better by 15% with IORT: IORT 2 events (96.7%, 95%CI 87.5-99.2), EBRT 9 events (81.7%, 95%CI 67.6-90.1), hazard ratio (HR) 0.19 (0.04-0.87), log rank p = 0.016, mainly due to a reduction of 10.1% in NBCM: IORT 100%, EBRT 89.9% (77.3-95.7), HR (not calculable), log rank p = 0.015. The DDFS was as follows: IORT 3 events (95.1%, 85.5-98.4), EBRT 12 events (69.0%, 49.1-82.4), HR 0.23 (0.06-0.80), log rank p = 0.012. CONCLUSION: IORT during lumpectomy after neoadjuvant chemotherapy as a tumour bed boost appears to give results that are not worse than external beam radiotherapy boost. These data give further support to the inclusion of such patients in the TARGIT-B (boost) randomised trial that is testing whether IORT boost is superior to EBRT boost.
EVALuna2:36210

Targeted sequencing of FH-deficient uterine leiomyomas reveals biallelic inactivating somatic fumarase variants and allows characterization of missense variants - Popp, Bernt; Erber, Ramona; Kraus, Cornelia; Vasileiou, Georgia; Hoyer, Juliane; Burghaus, Stefanie; Hartmann, Arndt; Beckmann, Matthias; Reis, André; Agaimy, Abbas (Modern Pathology, 2020)
Uterine leiomyomas (ULs) constitute a considerable health burden in the general female population. The fumarate hydratase (FH) deficient subtype is found in up to 1.6% and can occur in hereditary leiomyomatosis and renal cell carcinoma (HLRCC) syndrome. We sequenced 13 FH deficient ULs from a previous immunohistochemical screen using a targeted panel and identified biallelic FH variants in all. In eight, we found an FH point mutation (two truncating, six missense) with evidence for loss of the second allele. Variant allele-frequencies in all cases with a point mutation pointed to somatic variants. Spatial clustering of the identified missense variants in the lyase domain indicated altered fumarase oligomerization with subsequent degradation as explanation for the observed FH deficiency. Biallelic FH deletions in five tumors confirm the importance of copy number loss as mutational mechanism. By curating all pathogenic FH variants and calculating their population frequency, we estimate a carrier frequency of up to 1/2,563. Comparing with the prevalence of FH deficient ULs, we conclude that most are sporadic and estimate 2.7–13.9% of females with an FH deficient UL to carry a germline FH variant. Further prospective tumor/normal sequencing studies are needed to develop a reliable screening strategy for HLRCC in women with ULs.
CRIS-Team Scopus Importer:2020-07-10

TGFB-induced factor homeobox 1 (TGIF) expression in breast cancer - 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)
Background: Breast cancer (BC) is the most frequent female cancer and preferentially metastasizes to bone. The transcription factor TGFB-induced factor homeobox 1 (TGIF) is involved in bone metabolism. However, it is not yet known whether TGIF is associated with BC bone metastasis or patient outcome and thus of potential interest.
CRIS-Team WoS Importer:2021-09-10

The association between prenatal alcohol consumption and preschool child stress system disturbance - Grimm, Jennifer; Stemmler, Mark; Golub, Yulia; Schwenke, Eva; Goecke, Tamme W.; Fasching, Peter; Beckmann, Matthias; Kratz, Oliver; Moll, Gunther; Kornhuber, Johannes; Eichler, Anna (Developmental Psychobiology, 2021)
Background: Drinking alcohol during pregnancy is considered a risk factor for child development; however, child biomarkers of prenatal alcohol exposure have been rarely studied. We examined whether a meconium alcohol metabolite (ethyl glucuronide, EtG) was associated with child cortisol concentrations at primary school age. Methods: For 137 children, prenatal alcohol exposure was operationalized by the meconium biomarker EtG and by maternal self-reports during pregnancy. Two EtG cut-offs (EtG ≥10 ng/g and EtG ≥112 ng/g) were applied. Cortisol concentrations were measured in saliva and hair samples. Results: Children with EtG ≥10 ng/g showed significantly reduced hair cortisol concentrations (HCCs) (p =.050, (Formula presented.) = 0.042). For children with EtG ≥112 ng/g, the cortisol awakening response (CAR) was significantly decreased (p =.025, (Formula presented.) = 0.070). These effects were also present in correlational analyses with continuous EtG data, speaking for partly dose-dependent effects. Especially, within the EtG ≥112 ng/g group, the basal (CAR: rp = −.642, p =.120) and cumulative (HCC: rp = −.660, p =.107) cortisol parameters were associated with child emotional symptoms at medium effect size. Conclusions: The present study showed both the biological association of intrauterine alcohol exposure with the cortisol stress system, partly dose-dependent, and the functional association with emotional and behavioral symptoms.
CRIS-Team Scopus Importer:2020-10-16
Keywords: alcohol; biomarker; child; cortisol stress system; ethyl glucuronide; hypothalamus-pituitary-adrenal axis; intrauterine alcohol exposure; meconium; pregnancy

The association of prenatal attachment and perinatal factors with pre- and postpartum depression in first-time mothers - Goecke, T.; Voigt, F.; Faschingbauer, F.; Spangler, Gottfried; Beckmann, Matthias; Beetz, Andrea (Archives of Gynecology and Obstetrics, 2012)
Purpose: This prospective study investigated associations between prenatal attachment of adult first-time mothers to the unborn child, perinatal factors and levels of depression before and up to 18 months after delivery. Method: Primiparas (N = 161) without specific risk factors answered the following questionnaires during the last term of pregnancy (t1): Edinburgh Postnatal Depression Scale (EPDS), Maternal Antenatal Attachment Scale (MAAS), questionnaire on the schema of the unborn child, and a questionnaire about the pregnancy. Perinatal data were taken from the patients' files. The EPDS was answered 3 weeks (t2, N = 157), 6 months (t3, N = 159), and 18 months (t4, N = 132) postpartum. Results: During pregnancy, 16.9 % of the women indicated mild depressive symptoms, and 7.5 %, medium to severe symptoms of depression. Mild symptoms of depression were found in 25.5 % at t2, 10.1 % at t3, and 12.2 % at t4; medium to severe symptoms were reported by 7.6, 1.9 and 5.6 %, respectively. Women with low control during delivery (emergency Caesarean) showed a tendency for higher levels (p = 0.067) of depression at t3 than women with elective Caesarean did. The quality of prenatal attachment to the unborn child correlated negatively with depressive symptoms at t1-t4. Conclusions: The closer the prenatal attachment of a mother to her unborn child, the less symptoms of depression she reports during the last term of pregnancy and postpartum. Therefore, promoting good mother-child attachment during pregnancy might influence the level of postpartum depression. © Springer-Verlag 2012.

The Benefit of a Retrospective Pregnancy Anamnesis in Child and Adolescent Psychiatry: The Reliability of Maternal Self-Report during Childhood Development - Mestermann, Stefan; Fasching, Peter; Beckmann, Matthias; Gerlach, Jennifer; Kratz, Oliver; Moll, Gunther; Kornhuber, Johannes; Eichler, Anna (Children, 2023)
Pregnancy anamnesis is a crucial part of child and adolescent psychiatry diagnostics. In previous works, the reliability of retrospective maternal self-report on perinatal characteristics was heterogeneous. This prospective longitudinal study aimed to evaluate women’s recall of prenatal events in a within-subject design. A sample of 241 women gave a self-report on prenatal alcohol, smoking, partnership quality, pregnancy satisfaction, and obstetric complications during the 3rd trimester (t0), childhood (t1, 6–10 y), and adolescence (t2, 12–14 y). The intra-individual agreement was examined. The t0–t1–(t2) agreement was poor to substantial; this was highest for smoking and worst for obstetric complications, followed by alcohol (Fleiss’ κ = 0.719 to −0.051). There were significant t0–t1–(t2) differences for all pregnancy variables (p < 0.017), except for 3rd trimester satisfaction (p = 0.256). For alcohol (t0 25.8%, t1 17.4%, t2 41.0%) and smoking (t0 11.9%, t1 16.4%, t2 22.6%), the highest self-reported rates were found during adolescence. During childhood, fewer obstetric complications (t0 84.9%, t1 42.2%) and worse partnerships were reported (t0 M = 8.86, t1 M = 7.89). Thought to be due to social stigmata and memory effects, pregnancy self-reports cannot be precisely reproduced. Creating a respectful and trusting atmosphere is essential for mothers to give honest self-reports that are in the best interest of their children.
CRIS-Team Scopus Importer:2023-06-30
Keywords: alcohol; partnership; pregnancy; pregnancy satisfaction; prenatal; retrospective; risk perceptions; self-report; smoking

The BRCA2 c.68-7T > A variant is not pathogenic: A model for clinical calibration of spliceogenicity - Colombo, Mara; Lopez-Perolio, Irene; Meeks, Huong D.; Caleca, Laura; Parsons, Michael T.; Li, Hongyan; De Vecchi, Giovanna; Tudini, Emma; Foglia, Claudia; Mondini, Patrizia; Manoukian, Siranoush; Behar, Raquel; et al. (Human Mutation, 2018)
Although the spliceogenic nature of the BRCA2 c.68-7T > A variant has been demonstrated, its association with cancer risk remains controversial. In this study, we accurately quantified by real-time PCR and digital PCR (dPCR), the BRCA2 isoforms retaining or missing exon 3. In addition, the combined odds ratio for causality of the variant was estimated using genetic and clinical data, and its associated cancer risk was estimated by case-control analysis in 83,636 individuals. Co-occurrence in trans with pathogenic BRCA2 variants was assessed in 5,382 families. Exon 3 exclusion rate was 4.5-fold higher in variant carriers (13%) than controls (3%), indicating an exclusion rate for the c.68-7T > A allele of approximately 20%. The posterior probability of pathogenicity was 7.44 × 10-115 . There was neither evidence for increased risk of breast cancer (OR 1.03; 95% CI 0.86-1.24) nor for a deleterious effect of the variant when co-occurring with pathogenic variants. Our data provide for the first time robust evidence of the nonpathogenicity of the BRCA2 c.68-7T > A. Genetic and quantitative transcript analyses together inform the threshold for the ratio between functional and altered BRCA2 isoforms compatible with normal cell function. These findings might be exploited to assess the relevance for cancer risk of other BRCA2 spliceogenic variants.
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The Chorioallantoic Membrane Xenograft Assay as a Reliable Model for Investigating the Biology of Breast Cancer - Ranjan, Raphela A.; Muenzner, Julienne K.; Kunze, Philipp; Geppert, Carol-Immanuel; Rübner, Matthias; Hübner, Hanna; Fasching, Peter; Beckmann, Matthias; Bäuerle, Tobias; Hartmann, Arndt; Walther, Wolfgang; Eckstein, Markus; et al. (Cancers, 2023)
The chorioallantoic membrane (CAM) assay is an alternative in vivo model that allows for minimally invasive research of cancer biology. Using the CAM assay, we investigated phenotypical and functional characteristics (tumor grade, mitosis rate, tumor budding, hormone receptor (HR) and HER2 status, Ki-67 proliferation index) of two breast cancer cell lines, MCF-7 and MDA-MB-231, which resemble the HR+ (luminal) and triple-negative breast cancer (TNBC) subgroups, respectively. Moreover, the CAM results were directly compared with murine MCF-7- and MDA-MB-231-derived xenografts and human patient TNBC tissue. Known phenotypical and biological features of the aggressive triple-negative breast cancer cell line (MDA-MB-231) were confirmed in the CAM assay, and mouse xenografts. Furthermore, the histomorphological and immunohistochemical variables assessed in the CAM model were similar to those in human patient tumor tissue. Given the confirmation of the classical biological and growth properties of breast cancer cell lines in the CAM model, we suggest this in vivo model to be a reliable alternative test system for breast cancer research to reduce murine animal experiments.
CRIS-Team Scopus Importer:2023-04-14
Keywords: 3R; alternative in vivo model; CAM model; hormone receptor; HTB-26; MCF-7; MDA-MB-231; mouse xenograft; tumor aggressiveness

The clinical data intelligence project - Sonntag, Daniel; Tresp, Volker; Zillner, Sonja; Hammon, Matthias; Reis, André; Fasching, Peter; Sedlmayr, Martin; Ganslandt, Thomas; Prokosch, Hans-Ulrich; Budde, Clemens; Schmidt, Danilo; Hinrichs, Carl; et al. (Informatik-Spektrum, 2015)
UnivIS-Import:2017-12-18:Pub.2015.tech.IMMD.infome.thecli

The clinical relevance of serum vascular endothelial growth factor (VEGF) in correlation to circulating tumor cells and other serum biomarkers in patients with metastatic breast cancer - Banys-Paluchowski, Malgorzata; Witzel, Isabell; Riethdorf, Sabine; Pantel, Klaus; Rack, Brigitte; Janni, Wolfgang; Fasching, Peter; Aktas, Bahriye; Kasimir-Bauer, Sabine; Hartkopf, Andreas; Solomayer, Erich-Franz; Fehm, Tanja; et al. (Breast Cancer Research and Treatment, 2018)
VEGF is one of the most important angiogenesis-stimulating cytokines and has been previously shown to be overexpressed in several solid cancers. The aim of the present study was to assess the clinical relevance of serum VEGF (sVEGF) in a large cohort of metastatic breast cancer patients and to explore the relationship between sVEGF and other blood-based biomarkers.Two hundred fifty-three patients with metastatic breast cancer were enrolled in this prospective, multicentre study. Blood samples were collected before start of first-line or later-line treatment. sVEGF was quantified by a commercially available ELISA. Circulating tumor cells (CTCs) were detected using CellSearch and other biomarkers (EGFR, HER2, RAS p21, TIMP1, CAIX) by ELISA.Levels of sVEGF were determined in all patients, with a median concentration of 231 pg/ml. After a median follow-up of 19 months, median overall survival (OS) was 10.2 months in patients with sVEGF levels above the upper quartile (i.e. 367 pg/ml), while median OS has not been reached in patients with sVEGF < 367 pg/ml (p < 0.001). Median progression-free survival (PFS) was 4.8 months for patients with sVEGF >= 367 pg/ml versus 9.1 months with sVEGF levels < 367 pg/ml (p < 0.001). Patients with sVEGF levels >= 367 pg/ml and >= 5 CTCs had the shortest OS, while those with sVEGF < 367 pg/ml and non-elevated CTCs had the longest OS. CTCs, grading, line of therapy and RAS p21 were independent predictors of OS. sVEGF, line of therapy and CTCs were independent predictors of PFS in the multivariate analysis.Metastatic breast cancer patients with elevated levels of sVEGF have significantly worse clinical outcome. This finding supports the biological role of VEGF in breast cancer.Current Controlled Trials ISRCTN59722891 (DETECT).
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The concept of the certification system of the German Cancer Society and its impact on gynecological cancer care - Wesselmann, Simone; Beckmann, Matthias; Winter, A. (Archives of Gynecology and Obstetrics, 2014)
This article describes the status of gynecological cancer care in Germany and gives an overview of the certification of gynecological cancer care by the German Cancer Society (Deutsche Krebsgesellschaft DKG). The DKG certifies cancer centers to promote a high-quality level in the treatment of oncological patients.Searches were conducted in PubMed and ScienceDirect to identify the relevant literature. Catalog of requirements for centers certification as well as benchmark reports were used to characterize cancer care in centers certified by DKG.The certification system of the DKG has been developed to ensure comprehensive care for cancer patients in Germany. The criteria for certification are based on interdisciplinary and inter-professional care conforming to guidelines and specialist expertise. These requirements have been shown to improve structural and process quality, and thus satisfaction and health outcomes in patients.
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The contributions of breast density and common genetic variation to breast cancer risk - Vachon, Celine M.; Pankratz, V. Shane; Scott, Christopher G.; Häberle, Lothar; Ziv, Elad; Jensen, Matthew R.; Brandt, Kathleen R.; Whaley, Dana H.; Olson, Janet E.; Heusinger, Katharina; Hack, Carolin; Jud, Sebastian; et al. (Journal of the National Cancer Institute, 2015)
We evaluated whether a 76-locus polygenic risk score (PRS) and Breast Imaging Reporting and Data System (BI-RADS) breast density were independent risk factors within three studies (1643 case patients, 2397 control patients) using logistic regression models. We incorporated the PRS odds ratio (OR) into the Breast Cancer Surveillance Consortium (BCSC) risk-prediction model while accounting for its attributable risk and compared five-year absolute risk predictions between models using area under the curve (AUC) statistics. All statistical tests were two-sided. BI-RADS density and PRS were independent risk factors across all three studies (P interaction = .23). Relative to those with scattered fibroglandular densities and average PRS (2(nd) quartile), women with extreme density and highest quartile PRS had 2.7-fold (95% confidence interval [CI] = 1.74 to 4.12) increased risk, while those with low density and PRS had reduced risk (OR = 0.30, 95% CI = 0.18 to 0.51). PRS added independent information (P < .001) to the BCSC model and improved discriminatory accuracy from AUC = 0.66 to AUC = 0.69. Although the BCSC-PRS model was well calibrated in case-control data, independent cohort data are needed to test calibration in the general population.
EVALuna2:14513

The DETECT Study Concept - Metastatic breast cancer and circulating tumor cells - Schramm, A.; Friedl, T.; Rack, B.; Trapp, E.; Fasching, Peter; Taran, F-A.; Hartkopf, A.; Schneeweiss, A.; Mueller, V.; Aktas, B.; Pantel, K.; Meier-Stiegen, F.; et al. (2016)
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The Diagnosis, Treatment, and Aftercare of Cervical Carcinoma. - Beckmann, Matthias; Stübs, Frederik; Vordermark, Dirk; Koch, Martin Christoph; Horn, Lars Christian; Fehm, Tanja (Deutsches Ärzteblatt international, 2021)
BACKGROUND: Approximately 4380 cases of cervical carcinoma were diagnosed in Germany in 2016. In women who had not participated in early detection programs, cervical carcinoma was usually already in an advanced stage at the time of diagnosis. Certified structures for care in conformity with the existing guidelines are available. METHODS: The new German clinical practice guideline was revised with the participation of 50 medical societies under the expert guidance of the Guideline Program in Oncology, which includes the German Association of the Scientific Medical Societies (Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften, AWMF). A systematic literature review was conducted. Systematic reviews, meta-analyses, and randomized controlled trials (RCTs) were considered. RESULTS: The histologic tumor stage and lymph-node stage are essential determinants of the treatment strategy. The main innovation regarding surgical treatment is the revival of open hysterectomy (overall survival [minimally invasive vs open hysterectomy]: 94.04% vs 99.4%; hazard ratio [HR]: 6.00; 95% confidence interval [1.77; 20.30]). In addition, for tumors measuring 2 cm or less, sentinel node biopsy is recommended rather than radical pelvic lymphadenectomy. MRI-guided brachytherapy is an oblig atory component of radiochemotherapy (overall survival [radiochemotherapy with vs without brachytherapy]: 58.2% vs 46.2%, p<0.001). The standard palliative treatment consists of bevacizumab combined with a platinum-containing agent (overall survival: HR: 0.77 [0.62; 0.95]; p = 0.007). CONCLUSION: Despite the introduction of new treatments, the outcome of patients with advanced cervical carcinoma has not much improved. In the surgical treatment of cervical carcinoma, the open approach is now favored. The sentinel node biopsy technique has become well established for the surgical staging of small tumors. Controlled trials are needed so that the outcome of women with cervical carcinoma, particularly in its advanced and metastatic stages, can be improved.
EVALuna2:506686

The effect of bpV(HOpic) on in vitro activation of primordial follicles in cultured swine ovarian cortical strips - Raffel, Nathalie; Klemm, Katrin; Dittrich, Ralf; Hoffmann, Inge; Söder, Stefan; Beckmann, Matthias; Lotz, Laura (Reproduction in Domestic Animals, 2019)
The vanadate-derivative dipotassium bisperoxo (5-hydroxy-pyridine-2-carboxylic) oxovanadate (V) (bpV(HOpic)), a pharmacological inhibitor of phosphatase and tensin homolog (PTEN), has been used in ovarian follicle culture systems for activation of follicular growth in vitro and suggested to be responsible for primordial follicle survival through indirect Akt activation. For pig ovarian tissue, it is still not clear which culture medium needs to be used, as well as which factors and hormones could influence follicular development; this also applies to bpV(HOpic) exposure. Therefore, ovarian cortical strips from pigs were cultured in 1 µM bpV(HOpic) (N = 24) or control medium (N = 24) for 48 hr. Media were then replaced with control medium and all tissue pieces incubated for additional 4 days. The strips were embedded in paraffin for histological determination of follicle proportions at the end of the culture period and compared to histological sections from tissue pieces without cultivation, which had been embedded right after preparation; comparison of healthy follicles for each developmental stage was performed to quantify follicle survival and activation. After 6-day culture, follicle activation occurred in tissue samples from both cultured groups but significantly more follicles showed progression of follicular development in the presence of 1 µM bpV(HOpic). The amount of non-vital follicles was not significantly increased during cultivation. BpV(HOpic) affects pig ovarian follicle development by promoting the initiation of follicle growth and development, similar as in rodent species and humans.
CRIS-Team Scopus Importer:2019-06-28
Keywords: bpV (HOpic); fertiprotekt; follicle activation follicle reserve; in vitro culture; ovarian cortical tissue

The effect of participation in neoadjuvant clinical trials on outcomes in patients with early breast cancer - Brennan, Meghan; Gaß, Paul; Häberle, Lothar; Wang, Daidong; Hartmann, Arndt; Lux, Michael P.; Beckmann, Matthias; Untch, Michael; Fasching, Peter (Breast Cancer Research and Treatment, 2018)
BACKGROUND: Clinical trials can offer novel and more advanced and/or novel treatments to cancer patients in advance of them being approved and available for all patients. While several studies have examined the effect of clinical trial participation on prognosis, there has been no clear conclusion from these studies. Therefore, we chose to test the influence of trial participation on pathological complete response (pCR) and mastectomy rates after neoadjuvant chemotherapy. METHODS: In this retrospective study, all patients treated with neoadjuvant chemotherapy from 2001 to 2014 were selected. A total of 1038 patients with complete treatment, patient, and tumor characteristics were included. A total of 260 of those were treated in clinical trials. We examined whether study participation status in addition to commonly known predictors for pCR improves prediction of pCR. Similar analyses were conducted for the mastectomy rate outcome measure. Finally, survival analyses were also conducted as part of an exploratory analysis. RESULTS: Study participation was an independent predictor of pCR in addition to commonly known predictors. Adjusted odds ratio (OR) for trial participants versus non-participants was 1.53 (95% CI 1.03-2.28). Additionally, study participation improved the prediction of mastectomy risk. The adjusted OR for trial participants versus non-participants was 0.62 (95% CI 0.42-0.90). Subgroup-specific differences concerning the impact of study participation could not be shown for either pCR or mastectomy rate. Survival comparisons could not be conducted due to large differences in follow-up data in patients participating in clinical trials versus those who did not participate; however, pCR was a predictor of prognosis in both groups. CONCLUSION: Patients taking part in neoadjuvant chemotherapy clinical trials have a higher pCR rate and a lower mastectomy risk than patients not participating in clinical trials for their cancer care. This finding is a supporting factor for trial participation in neoadjuvant chemotherapy trials.
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The FANCM:p.Arg658* truncating variant is associated with risk of triple-negative breast cancer - Figlioli, Gisella; Bogliolo, Massimo; Catucci, Irene; Caleca, Laura; Lasheras, Sandra Viz; Pujol, Roser; Kiiski, Johanna I.; Muranen, Taru A.; Barnes, Daniel R.; Dennis, Joe; Michailidou, Kyriaki; Bolla, Manjeet K.; et al. (npj Breast Cancer, 2019)
Breast cancer is a common disease partially caused by genetic risk factors. Germline pathogenic variants in DNA repair genes BRCA1, BRCA2, PALB2, ATM, and CHEK2 are associated with breast cancer risk. FANCM, which encodes for a DNA translocase, has been proposed as a breast cancer predisposition gene, with greater effects for the ER-negative and triple-negative breast cancer (TNBC) subtypes. We tested the three recurrent protein-truncating variants FANCM:p.Arg658*, p.Gln1701*, and p.Arg1931* for association with breast cancer risk in 67,112 cases, 53,766 controls, and 26,662 carriers of pathogenic variants of BRCA1 or BRCA2. These three variants were also studied functionally by measuring survival and chromosome fragility in FANCM−/− patient-derived immortalized fibroblasts treated with diepoxybutane or olaparib. We observed that FANCM:p.Arg658* was associated with increased risk of ER-negative disease and TNBC (OR = 2.44, P = 0.034 and OR = 3.79; P = 0.009, respectively). In a country-restricted analysis, we confirmed the associations detected for FANCM:p.Arg658* and found that also FANCM:p.Arg1931* was associated with ER-negative breast cancer risk (OR = 1.96; P = 0.006). The functional results indicated that all three variants were deleterious affecting cell survival and chromosome stability with FANCM:p.Arg658* causing more severe phenotypes. In conclusion, we confirmed that the two rare FANCM deleterious variants p.Arg658* and p.Arg1931* are risk factors for ER-negative and TNBC subtypes. Overall our data suggest that the effect of truncating variants on breast cancer risk may depend on their position in the gene. Cell sensitivity to olaparib exposure, identifies a possible therapeutic option to treat FANCM-associated tumors.
CRIS-Team Scopus Importer:2019-11-12

The Father’s Part: Influences of Paternal Psychopathology and Parenting Behavior on Child and Adolescent Well-Being - Mestermann, Stefan; Arndt, Marie; Fasching, Peter; Beckmann, Matthias; Kratz, Oliver; Moll, Gunther; Kornhuber, Johannes; Eichler, Anna (Healthcare, 2023)
Family influences on child quality of life (QoL) are increasingly understood. Parenting behavior and parent individual psychopathology are among the established predictors of offspring mental health. However, literature often addresses these factors as ‘parental’, lacking further gender-specific differentiation while predominantly studying maternal aspects. Social and biological fathers are still underrepresented in family research. The aim of this study was to analyze paternal contributions to child well-being. A total of 197 father/mother-dyads gave a standardized self-report on parenting behavior and their own psychopathology at child primary school age (t1; 6–10 y). Ratings were compared mutually and associated with child self-rated QoL at t1 and adolescence (t2; 12–14 y). Fathers and mothers differed in psychopathology and most parenting behavior dimensions (positive parenting, involvement, responsible parenting, poor monitoring, and corporal punishment). Father psychopathology made a relevant predictive contribution to girls’ QoL at t2. Boys’ t1 QoL was significantly influenced by maternal parenting factors (positivity and corporal punishment). Compared to mothers, fathers are faced with different individual stressors; paternal parenting behavior is different, while fathers’ influences are significant, particularly for daughters. Father-addressed pre- and intervention programs in child psychotherapeutic treatment are of high relevance.
CRIS-Team Scopus Importer:2023-08-25
Keywords: child development; father; parent-child-relations; parental influence; parenting; parenting behavior; resilience

The genetic interplay between body mass index, breast size and breast cancer risk: a Mendelian randomization analysis - Ooi, Brandon Nick Sern; Loh, Huiwen; Ho, Peh Joo; Milne, Roger L.; Giles, Graham; Gao, Chi; Kraft, Peter; John, Esther M.; Swerdlow, Anthony; Brenner, Hermann; Wu, Anna H.; Haiman, Christopher; et al. (International Journal of Epidemiology, 2019)
BACKGROUND: Evidence linking breast size to breast cancer risk has been inconsistent, and its interpretation is often hampered by confounding factors such as body mass index (BMI). Here, we used linkage disequilibrium score regression and two-sample Mendelian randomization (MR) to examine the genetic associations between BMI, breast size and breast cancer risk. METHODS: Summary-level genotype data from 23andMe, Inc (breast size, n = 33 790), the Breast Cancer Association Consortium (breast cancer risk, n = 228 951) and the Genetic Investigation of ANthropometric Traits (BMI, n = 183 507) were used for our analyses. In assessing causal relationships, four complementary MR techniques [inverse variance weighted (IVW), weighted median, weighted mode and MR-Egger regression] were used to test the robustness of the results. RESULTS: The genetic correlation (rg) estimated between BMI and breast size was high (rg = 0.50, P = 3.89x10-43). All MR methods provided consistent evidence that higher genetically predicted BMI was associated with larger breast size [odds ratio (ORIVW): 2.06 (1.80-2.35), P = 1.38x10-26] and lower overall breast cancer risk [ORIVW: 0.81 (0.74-0.89), P = 9.44x10-6]. No evidence of a relationship between genetically predicted breast size and breast cancer risk was found except when using the weighted median and weighted mode methods, and only with oestrogen receptor (ER)-negative risk. There was no evidence of reverse causality in any of the analyses conducted (P > 0.050). CONCLUSION: Our findings indicate a potential positive causal association between BMI and breast size and a potential negative causal association between BMI and breast cancer risk. We found no clear evidence for a direct relationship between breast size and breast cancer risk.
CRIS-Team Scopus Importer:2019-09-17
Keywords: body mass index; breast cancer risk; Breast size; genetic correlation; genetic epidemiology; LDSC regression; Mendelian randomization

The Hallmarks of Endometriosis Markenzeichen von Endometriose - Psilopatis, Iason; Burghaus, Stefanie; Au, Katharina; Hofbeck, Louisa; Windischbauer, Lisa-Maria; Lotz, Laura; Beckmann, Matthias (Geburtshilfe und Frauenheilkunde, 2024)
A heuristic tool called the hallmarks of cancer helps to reduce the enormous complexity of cancer phenotypes and genotypes to a preliminary set of guiding principles. Other aspects of cancer have surfaced as possible improvements in our understanding of the disease's mechanisms. Endometriosis is a gynecological disease condition negatively impacting the quality of life of many women. To date, there is no curative treatment for endometriosis. Therapy is aimed at treating the symptoms using hormone therapy, pain therapy and complementary therapy. Chronic pain and overlapping pain syndromes and illnesses can also be treated with multimodal pain therapy and psychosomatic therapy. Endometriosis is, however, a chronic and complex entity which, in this regard, resembles cancer. The present work investigates the hallmarks of endometriosis with a view to summarizing the current research status and paving new ways for future research projects.
CRIS-Team Scopus Importer:2024-06-28
Keywords: endometriosis; epigenetics; genetics; molecular; pathway; signaling

The HER2 phenotype of circulating tumor cells in HER2-positive early breast cancer: A translational research project of a prospective randomized phase III trial - Jaeger, B. A. S.; Neugebauer, J.; Andergassen, U.; Melcher, C.; Schochter, F.; Mouarrawy, D.; Ziemendorff, G.; Clemens, M.; Abel, E. V.; Heinrich, G.; Schueller, K.; Schneeweiss, A.; et al. (PLoS ONE, 2017)
BACKGROUND: HER2 is one of the predominant therapeutic targets in breast cancer. The metastatic selection process may lead to discrepancies between the HER2 status of the primary tumor and circulating tumor cells (CTCs). This study analyzed the HER2 status of CTCs in patients with HER2-positive primary breast cancer at the time of diagnosis. Aim of the study was to assess potential discordance of HER2 status between primary tumor and CTCs, as this may have important implications for the use of HER2-targeted therapy. METHODS: The number and HER2 status of CTCs out of 30ml peripheral blood were assessed in 642 patients using the CellSearch System (Janssen Diagnostics, USA). The cutoff for CTC positivity was the presence of at least 1 CTC, and the cutoff for HER2 positivity of CTCs was the presence of at least 1 CTC with a strong HER2 staining. RESULTS: 258 (40.2%) of the 642 patients were positive for CTCs (median 2; range 1-1,689). 149 (57.8%) of these 258 patients had at least 1 CTC with strong HER2 staining. The presence of HER2-positive CTCs was not associated with tumor size (p = 0.335), histopathological grading (p = 0.976), hormone receptor status (ER: p = 0.626, PR: p = 0.263) or axillary lymph node involvement (p = 0.430). Overall, 83 (32.2%) of the CTC-positive patients exclusively had CTCs with strong HER2 staining, whereas 31 (12.0%) had only CTCs with negative HER2 staining. Within-sample variation in the HER2 status of CTCs was found in 86 (57.8%) of the 149 patients with more than 1 CTC. CONCLUSION: This study demonstrated that discordance between the HER2 expression of CTCs and that of the primary tumor frequently occurs in early breast cancer. Future follow-up evaluation will assess whether this discrepancy may contribute to trastuzumab resistance.
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The impact of anthracyclines in intermediate and high-risk HER2-negative early breast cancer-a pooled analysis of the randomised clinical trials PlanB and SUCCESS C - De Gregorio, Amelie; Janni, Wolfgang; Friedl, Thomas W. P.; Nitz, Ulrike; Rack, Brigitte; Schneeweiss, Andreas; Kates, Ronald; Fehm, Tanja; Kreipe, Hans; Christgen, Matthias; Kuemmel, Sherko; Trapp, Elisabeth; et al. (British Journal of Cancer, 2022)
Background Anthracycline/cyclophosphamide-taxane-containing chemotherapy (AC-T) is the standard of care in the adjuvant treatment of HER2-negative early breast cancer (EBC), but recent studies suggest omission of anthracyclines for reduced toxicity without compromising efficacy. Methods Based on individual patient data (n = 5924) pooled from the randomised Phase III trials PlanB and SUCCESS C, we compared disease-free survival (DFS) and overall survival (OS) between intermediate to high-risk HER2-negative EBC-patients treated with either six cycles of docetaxel/cyclophosphamide (TC6) or an AC-T regime using univariable and adjusted multivariable Cox regression models. Results AC-T conferred no significant DFS or OS advantage in univariable (DFS: hazard ratio (HR) for TC vs. AT 1.05, 95% confidence interval (CI): 0.89-1.24, P = 0.57; OS: HR 1.00, 95% CI: 0.80-1.26, P = 1.00) and adjusted multivariable analysis (DFS: HR 1.01, 95% CI: 0.86-1.19, P = 0.91; OS: HR 0.97, 95% CI: 0.77-1.22, P = 0.79). Patients receiving TC6 had significantly fewer grade 3-4 adverse events. Exploratory subgroup analysis showed that AC-T was associated with significantly better DFS and OS in pN2/3 patients, specifically in those with lobular histology. Conclusion For most patients with HER2-negative EBC, AC-T is not associated with a survival benefit compared to TC6. However, patients with lobular pN2/pN3 tumours seem to benefit from anthracycline-containing chemotherapy.
CRIS-Team WoS Importer:2022-03-18

The impact of mammalian target of rapamycin inhibition on bone health in postmenopausal women with hormone receptor-positive advanced breast cancer receiving everolimus plus exemestane in the phase IIIb 4EVER trial - Hadji, Peyman; Stoetzer, Oliver; Decker, Thomas; Kurbacher, Christian M.; Marme, Frederik; Schneeweiss, Andreas; Mundhenke, Christoph; Distelrath, Andrea; Fasching, Peter; Lux, Michael P.; Lueftner, Diana; Janni, Wolfgang; et al. (Journal of Bone Oncology, 2019)
Background: Breast cancer and its treatments are associated with a detrimental effect on bone health. Here we report the results of an exploratory analysis assessing changes in levels of biomarkers of bone metabolism in patients enrolled in the phase IIIb 4EVER study.
CRIS-Team WoS Importer:2019-03-20

The impact of physical activity on progression-free and overall survival in metastatic breast cancer based on molecular subtype - Ziegler, Philipp; Hartkopf, Andreas D.; Wallwiener, Markus; Häberle, Lothar; Kolberg, Hans Christian; Hadji, Peyman; Tesch, Hans; Ettl, Johannes; Lüftner, Diana; Müller, Volkmar; Michel, Laura L.; Belleville, Erik; et al. (BMC Cancer, 2024)
Background: Although adequate physical activity has been shown to be beneficial in early breast cancer, evidence in metastatic breast cancer is sparse and contradictory, which could be related to distinct effects of physical activity on the different molecular cancer subtypes. Therefore, we here evaluated the effect of physical activity on progression-free and overall survival (PFS, OS) in metastatic breast cancer, specifically looking at molecular subtypes. Methods: International Physical Activity Questionnaire (IPAQ) questionnaires, filled out by patients enrolled in the prospective PRAEGNANT registry (NCT02338167; n = 1,270) were used to calculate metabolic equivalent task (MET) minutes, which were subsequently categorized into low (n = 138), moderate (n = 995) or high IPAQ categories (n = 137). Cox regression analyses were used to evaluate the impact of IPAQ categories and its interaction with molecular subtypes on PFS and OS. Results: Patient and tumor characteristics were equally distributed across IPAQ categories. HER2pos, HRpos and TNBC were present in 23.1%, 65.7% and 11.2% of patients, respectively. IPAQ scores did not have an impact on PFS and OS in addition to established prognostic factors, either overall or in particular molecular subtypes (PFS: p = 0.33 and OS: p = 0.08, likelihood ratio test). Exploratory analyses showed higher overall survival rates for high IPAQ categories compared to low/moderate IPAQ categories in luminal B-like breast cancer. Conclusions: Self-reported physical activity using the IPAQ questionnaire did not significantly affect PFS or OS in patients suffering from metastatic breast cancer. Nevertheless, some hypothesis-generating differences between molecular subtypes could be observed, which may be interesting to evaluate further.
CRIS-Team Scopus Importer:2024-10-25
Keywords: IPAQ; Metastatic breast cancer; Molecular subtype; Physical activity

The influence of obesity on survival in early, high-risk breast cancer: results from the randomized SUCCESS A trial - Widschwendter, Peter; Friedl, Thomas W. P.; Schwentner, Lukas; Degregorio, Nikolaus; Jaeger, Bernadette; Schramm, Amelie; Bekes, Inga; Deniz, Miriam; Lato, Krisztian; Weissenbacher, Tobias; Kost, Bernd; Andergassen, Ulrich; et al. (Breast Cancer Research, 2015)
Obese breast cancer patients have worse prognosis than normal weight patients, but the level at which obesity is prognostically unfavorable is unclear.This retrospective analysis was performed using data from the SUCCESS A trial, in which 3754 patients with high-risk early breast cancer were randomized to anthracycline- and taxane-based chemotherapy with or without gemcitabine. Patients were classified as underweight/normal weight (body mass index (BMI) < 25.0), overweight (BMI 25.0-29.9), slightly obese (BMI 30.0-34.9), moderately obese (BMI 35.0-39.9) and severely obese (BMI >= 40.0), and the effect of BMI on disease-free survival (DFS) and overall survival (OS) was evaluated (median follow-up 65 months). In addition, subgroup analyses were conducted to assess the effect of BMI in luminal A-like, luminal B-like, HER2 (human epidermal growth factor 2)-positive and triple-negative tumors.Multivariate analyses revealed an independent prognostic effect of BMI on DFS (p = 0.001) and OS (p = 0.005). Compared with underweight/normal weight patients, severely obese patients had worse DFS (hazard ratio (HR) 2.70, 95 % confidence interval (CI) 1.71-4.28, p < 0.001) and OS (HR 2.79, 95 % CI 1.63-4.77, p < 0.001), while moderately obese, slightly obese and overweight patients did not differ from underweight/normal weight patients with regard to DFS or OS. Subgroup analyses showed a similar significant effect of BMI on DFS and OS in patients with triple-negative breast cancer (TNBC), but not in patients with other tumor subtypes.Severe obesity (BMI >= 40) significantly worsens prognosis in early breast cancer patients, particularly for triple-negative tumors.Clinicaltrials.gov NCT02181101 . Registered September 2005.
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The Influence of Physical Training on Breast Cancer: The Role of Exercise-Induced Myokines in Regulating Breast Cancer Cell Growth and Survival - Natarajan, Anirudh; Pradhan, Rashmita; Dieterich, Walburga; Schwappacher, Raphaela; Reljic, Dejan; Herrmann, Hans Joachim; Neurath, Markus; Hack, Carolin; Beckmann, Matthias; Zopf, Yurdagül (International Journal of Molecular Sciences, 2024)
The beneficial impact of physical training in lowering cancer risk is well known. However, the precise mechanisms linking physical training and cancer are not fully understood. Skeletal muscle releases various myokines that seem to possess a direct anti-tumor effect. Although breast cancer (BC) is the prevalent form of cancer among women on a global scale, only limited data are available about the secretion of myokines following exercise in patients with BC. To study the effects of exercise on BC, the blood samples of patients with varied stages of BC were analyzed after 12 weeks of resistance training with whole-body electromyostimulation (WB-EMS). Following the training period, we observed that resistance training helps these patients to improve their physical characteristics and performance function by increasing skeletal muscle mass and strengthening their hand grip. Notably, the patient’s serum was found to inhibit the growth and promote the apoptosis of BC cells in vitro. Moreover, the conditioned medium collected from in vitro stimulated human myotubes using electric pulse stimulation (EPS), an in vitro simulation of WB-EMS training, induced the cell death of BC cells. These results highlighted the direct cancer-protective effects of activated skeletal muscle. In line with our observed effects of serum from exercise-trained pancreatic and prostate cancer patients, the growth of BC cells was notably inhibited when supplemented directly with recombinant myokines C-X-C motif ligand 1 (CXCL1), Interleukin 10 (IL10), and C-C motif chemokine ligand 4 (CCL4). Notably, treatment with these myokines also increased the expression of caspase 3/7 (Casp3/7), resulting in enhanced BC cell death. Our data strongly suggest that physical exercise has a positive impact on skeletal muscle mass and hand grip strength in BC patients, along with a significant anti-tumor effect in BC cells. This shows promising potential for considering sports and physical training as supportive therapies for achieving more impactful cancer treatment.
CRIS-Team Scopus Importer:2024-11-22
Keywords: apoptosis; breast cancer; electric pulse stimulation; myokines; proliferation; resistance training; whole-body electromyostimulation

The influence of prenatal risks on attachment, emotion regulation and emotional and behavioral problems in middle childhood: A prospective longitudinal study - Ziegler, Clara; Zalan, Vera; Eichler, Anna; Heinrich, Hartmut; Moll, Gunther; Fasching, Peter; Beckmann, Matthias; Kornhuber, Johannes; Lenz, Bernd; Spangler, Gottfried (International Attachment Conference, 2017)

The integrative epigenomic-transcriptomic landscape of ER positive breast cancer - Gao, Yang; Jones, Allison; Fasching, Peter; Rübner, Matthias; Beckmann, Matthias; Widschwendter, Martin; Teschendorff, Andrew E. (Clinical Epigenetics, 2015)
While recent integrative analyses of copy number and gene expression data in breast cancer have revealed a complex molecular landscape with multiple subtypes and many oncogenic/tumour suppressor driver events, much less is known about the role of DNA methylation in shaping breast cancer taxonomy and defining driver events.Here, we applied a powerful integrative network algorithm to matched DNA methylation and RNA-Seq data for 724 estrogen receptor (ER)-positive (ER+) breast cancers and 111 normal adjacent tissue specimens from The Cancer Genome Atlas (TCGA) project, in order to identify putative epigenetic driver events and to explore the resulting molecular taxonomy. This revealed the existence of nine functionally deregulated epigenetic hotspots encompassing a total of 146 genes, which we were able to validate in independent data sets encompassing over 1000 ER+ breast cancers. Integrative clustering of the matched messenger RNA (mRNA) and DNA methylation data over these genes resulted in only two clusters, which correlated very strongly with the luminal-A and luminal B subtypes. Overall, luminal-A and luminal-B breast cancers shared the same epigenetically deregulated hotspots but with luminal-B cancers exhibiting increased aberrant DNA methylation patterns relative to normal tissue. We show that increased levels of DNA methylation and mRNA expression deviation from the normal state define a marker of poor prognosis. Our data further implicates epigenetic silencing of WNT signalling antagonists and bone morphogenetic proteins (BMP) as key events underlying both luminal subtypes but specially of luminal-B breast cancer. Finally, we show that DNA methylation changes within the identified epigenetic interactome hotspots do not exhibit mutually exclusive patterns within the same cancer sample, instead exhibiting coordinated changes within the sample.Our results indicate that the integrative DNA methylation and transcriptomic landscape of ER+ breast cancer is surprisingly homogeneous, defining two main subtypes which strongly correlate with luminal-A/B subtype status. In particular, we identify WNT and BMP signalling as key epigenetically deregulated tumour suppressor pathways in luminal ER+ breast cancer, with increased deregulation seen in luminal-B breast cancer.
EVALuna2:17561

The International Endometriosis Evaluation Program (IEEP Study) - A Systematic Study for Physicians, Researchers and Patients - Burghaus, Stefanie; Fehm, T.; Fasching, Peter; Blum, Simon; Renner, Stefan; Baier, F.; Brodkorb, T.; Fahlbusch, C.; Findeklee, S.; Häberle, Lothar; Heusinger, K.; Hildebrandt, T.; et al. (Geburtshilfe und Frauenheilkunde, 2016)
INTRODUCTION: Endometriosis is a heterogeneous disease characterized by a range of different presentations. It is usually diagnosed when patients present with pain and/or infertility, but it has also been diagnosed in asymptomatic patients. Because of the different diagnostic approaches and diverse therapies, time to diagnosis can vary considerably and the definitive diagnosis may be delayed, with some cases not being diagnosed for several years. Endometriosis patients have many unmet needs. A systematic registration and follow-up of endometriosis patients could be useful to obtain an insight into the course of the disease. The validation of biomarkers could contribute to the development of diagnostic and predictive tests which could help select patients for surgical assessment earlier and offer better predictions about patients who might benefit from medical, surgical or other interventions. The aim is also to obtain a better understanding of the etiology, pathogenesis and progression of the disease. MATERIAL AND METHODS: To do this, an online multicenter documentation system was introduced to facilitate the establishment of a prospective multicenter case-control study, the IEEP (International Endometriosis Evaluation Program) study. We report here on the first 696 patients with endometriosis included in the program between June 2013 and June 2015. RESULTS: A documentation system was created, and the structure and course of the study were mapped out with regard to data collection and the collection of biomaterials. CONCLUSION: The documentation system permits the history and clinical data of patients with endometriosis to be recorded. The IEEP combines this information with biomaterials and uses it for scientific studies. The recorded data can also be used to evaluate clinical quality control measures such as the certification parameters used by the EEL (European Endometriosis League) to assess certified endometriosis centers.
EVALuna2:32966

The PI3K Pathway: Background and Treatment Approaches - Lux, Michael P.; Fasching, Peter; Schrauder, Michael G.; Hein, Alexander; Jud, Sebastian; Rauh, Claudia; Beckmann, Matthias (Breast Care, 2016)
Two-thirds of all breast cancer patients with metastases have a hormone receptor (HR)-positive/human epidermal growth factor receptor 2 (HER2)-negative subtype. Endocrine therapy is the treatment of choice in these patients since in addition to its effectiveness it can also maintain the patients' quality of life over a longer term. However, 44-62% of postmenopausal patients with metastatic breast carcinoma have primary tamoxifen resistance. After 3-5 years, 30-40% of the patients receiving tamoxifen treatment develop secondary resistance. Understanding the way in which resistance develops is therefore essential for developing treatment approaches that can prevent or reverse endocrine resistance. The phosphatidylinositol 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) signaling pathway plays a central role here. As a result of the numerous interactions involved, complex issues arise that need to be taken into account in the development and use of therapeutic agents. In addition, this signaling pathway is the one that most frequently undergoes mutations in breast cancer. The prognostic and predictive significance of individual mutations has not yet been fully explained, but it might provide a basis for patient selection in clinical studies. Initial research results on the use of PI3K inhibitors suggest that this may be a highly promising therapeutic approach, with an acceptable side effect profile.
EVALuna2:33003

The placental mTOR-pathway: correlation with early growth trajectories following intrauterine growth restriction? - Fahlbusch, F. B.; Menendez-Castro, C.; Nögel, Stephanie; Marek, I.; Beckmann, Matthias; Schleussner, E.; Ruebner, M.; Huebner, H.; Dörr, Helmuth-Günther; Schild, R. L.; Doetsch, J.; Rascher, Wolfgang; et al. (Journal of Developmental Origins of Health and Disease, 2015)
Idiopathic intrauterine growth restriction (IUGR) is a result of impaired placental nutrient supply. Newborns with IUGR exhibiting postnatal catch-up growth are of higher risk for cardiovascular and metabolic co-morbidities in adult life. Mammalian target of rapamycin (mTOR) was recently shown to function as a placental nutrient sensor. Thus, we determined possible correlations of members of the placental mTOR signaling cascade with auxologic parameters of postnatal growth. The protein expression and activity of mTOR-pathway signaling components, Akt, AMP-activated protein kinase ?, mTOR, p70S6kinase1 and insulin receptor substrate-1 were analysed via western blotting in IUGR v. matched appropriate-for-gestational age (AGA) placentas. Moreover, mTOR was immunohistochemically stained in placental sections. Data from western blot analyses were correlated with retrospective auxological follow-up data at 1 year of age. We found significant catch-up growth in the 1st year of life in the IUGR group. MTOR and its activated form are immunohistochemically detected in multiple placental compartments. We identified correlations of placental mTOR-pathway signaling components to auxological data at birth and at 1 year of life in IUGR. Analysis of the protein expression and phosphorylation level of mTOR-pathway components in IUGR and AGA placentas postpartum, however, did not reveal pathognomonic changes. Our findings suggest that the level of activated mTOR correlates with early catch-up growth following IUGR. However, the complexity of signals converging at the mTOR nexus and its cellular distribution pattern seem to limit its potential as biomarker in this setting.
EVALuna2:17439

The prognostic relevance of urokinase-type plasminogen activator (uPA) in the blood of patients with metastatic breast cancer - Banys-Paluchowski, Malgorzata; Witzel, Isabell; Aktas, Bahriye; Fasching, Peter; Hartkopf, Andreas; Janni, Wolfgang; Kasimir-Bauer, Sabine; Pantel, Klaus; Schoen, Gerhard; Rack, Brigitte; Riethdorf, Sabine; Solomayer, Erich-Franz; et al. (Scientific Reports, 2019)
In breast cancer (BC), elevated levels of urokinase-type plasminogen activator (uPA) in tumor tissue have been confirmed as a strong prognostic factor in level-of-evidence-1 studies. The aim of the present study was to evaluate the clinical relevance of uPA levels in serum of metastatic BC patients and to compare uPA with other blood-based biomarkers. 252 patients were enrolled in this prospective, multicentre study. Blood samples were collected before begin of first-line or later-line systemic treatment. Serum uPA was quantified by a commercially available ELISA. Circulating tumor cells (CTCs) were detected using CellSearch; other biomarkers (EGFR, VEGF, HER2, RAS p21, TIMP1, CAIX) by ELISA. Using the ROC analysis, the optimal cut-off value (determined by the Youden index) of serum uPA was 2.52 ng/ml. Using this value, 26% of patients had elevated uPA levels. Patients with visceral metastasis and more than one metastatic site were significantly more likely to present with elevated uPA levels. CTC status, serum HER2, RAS p21, CAIX, TIMP1 and VEGF correlated significantly with uPA levels. Elevated uPA levels predicted shorter overall and progression-free survival in univariate analysis (median OS: 7.5 months [95%-CI 4.5-10.5 months] vs. not reached, p < 0.001; PFS:4.8 [95%CI: 3.1-6.5] vs. 9.1 [7.4-10.8] months, p < 0.001). In multivariate analysis, elevated uPA, presence of >= 5 CTCs, elevated RAS p21, higher grading and higher line of therapy were independent predictors of shorter OS, while elevated CTC counts, higher line of therapy and negative estrogen receptor status were independent predictors of shorter PFS. In conclusion, elevated uPA levels independently predict reduced overall survival and improved prognostication in patients with known CTC status. Whether high serum uPA might identify patients most likely to benefit from therapies targeting uPA, remains to be evaluated in future trials.
CRIS-Team WoS Importer:2019-03-06

The Randomized AMBORA Trial: Impact of Pharmacological/Pharmaceutical Care on Medication Safety and Patient-Reported Outcomes During Treatment With New Oral Anticancer Agents - Dürr, Pauline; Schlichtig, Katja; Kelz, Carolin; Deutsch, Birgit; Maas, Renke; Eckart, Michael J.; Wilke, Jochen; Wagner, Harald; Wolff, Kerstin; Preuß, Caroline; Brückl, Valeska; Meidenbauer, Norbert; et al. (Journal of Clinical Oncology, 2021)
PURPOSE: Oral anticancer drugs (eg, kinase inhibitors) play an important role in cancer therapy. However, considerable challenges regarding medication safety of oral anticancer drugs have been reported. Randomized, controlled, multicenter studies on the impact of intensified clinical pharmacological/pharmaceutical care on patient safety and patient treatment perception are lacking. METHODS: Patients were eligible for the randomized, multicenter AMBORA study, if they were newly started on any of the oral anticancer drugs approved in 2001 or later without restriction to certain tumor entities. Patients were randomly assigned to receive either standard of care (control group) or an additional, intensified clinical pharmacological/pharmaceutical care, which included medication management and structured patient counseling, over a period of 12 weeks (intervention group). Primary end points were the number of antitumor drug-related problems (ie, side effects and unresolved medication errors) and patient treatment satisfaction with the oral anticancer therapy after 12 weeks measured with the Treatment Satisfaction Questionnaire for Medication, category convenience. RESULTS: Two hundred two patients were included. Antitumor drug-related problems were significantly lower in the intervention compared with the control group (3.85 v 5.81 [mean], P < .001). Patient treatment satisfaction was higher in the intervention group (Treatment Satisfaction Questionnaire for Medication, convenience; 91.6 v 74.4 [mean], P < .001). The hazard ratio for the combined end point of severe side effects (Common Terminology Criteria for Adverse Events ≥ 3), treatment discontinuation, unscheduled hospital admission, and death was 0.48 (95% CI, 0.32 to 0.71, P < .001) in favor of the intervention group. CONCLUSION: Treatment with oral anticancer drugs is associated with a broad range of medication errors and side effects. An intensified clinical pharmacological/pharmaceutical care has considerable, positive effects on the number of medication errors, patient treatment perception, and severe side effects.
CRIS-Team Scopus Importer:2021-07-02

Therapierelevante Biomarker in der gynäkologischen Onkologie - Ditsch, Nina; Fasching, Peter (Best Practice Onkologie, 2022)
The first biomarkers were discovered decades ago. Their prognostic and predictive value is still the subject of current research. Biomarker-based treatments represent the basis of the current and future trial landscape in gynecologic oncology, as was clearly demonstrated at this year’s ASCO Annual Meeting. The all-important question is founded in the quality of diagnostics at the immunohistochemical or molecular level. In breast cancer therapy, a HER‑2 (human epidermal growth factor receptor 2) finding was previously considered therapeutically relevant if there was an immunohistochemical (IHC) evaluation of 3+ or a fluorescence in situ hybridization (FISH)- or chromogenic in situ hybridization (CISH)-positive value. Use of the antibody–drug conjugate trastuzumab–deruxtecan, also in HER-2-low forms (IHC1+ or 2+, even if FISH/CISH negative), is now celebrated as practice changing, since significantly improved progression-free survival (PFS) and overall survival (OS) were also shown in this situation. With the accelerating use of newer therapeutics, attention should be paid to the side effects and the cost–benefit ratio. The following article provides an overview of the currently most important prognostic and predictive markers in breast, ovarian, endometrial, and cervical cancer.
CRIS-Team Scopus Importer:2022-11-11
Keywords: Her-2; Immune checkpoint inhibitors; Immunoconjugates; Microsatellite instability; Prognosis; Trastuzumab

Therapy landscape in patients with metastatic HER2-positive breast cancer: Data from the PRAEGNANT real-world breast cancer registry - Lux, Michael P.; Nabieva, Naiba; Hartkopf, Andreas D.; Huober, Jens; Volz, Bernhard; Taran, Florin-Andrei; Overkamp, Friedrich; Kolberg, Hans-Christian; Hadji, Peyman; Tesch, Hans; Häberle, Lothar; Ettl, Johannes; et al. (Cancers, 2019)
This study presents comprehensive real-world data on the use of anti-human epidermal growth factor receptor 2 (HER2) therapies in patients with HER2-positive metastatic breast cancer (MBC). Specifically, it describes therapy patterns with trastuzumab (H), pertuzumab + trastuzumab (PH), lapatinib (L), and trastuzumab emtansine (T-DM1). The PRAEGNANT study is a real-time, real-world registry for MBC patients. All therapy lines are documented. This analysis describes the utilization of anti-HER2 therapies as well as therapy sequences. Among 1936 patients in PRAEGNANT, 451 were HER2-positive (23.3%). In the analysis set (417 patients), 53% of whom were included in PRAEGNANT in the first-line setting, 241 were treated with H, 237 with PH, 85 with L, and 125 with T-DM1 during the course of their therapies. The sequence PH ! T-DM1 was administered in 51 patients. Higher Eastern Cooperative Oncology Group (ECOG) scores, negative hormone receptor status, and visceral or brain metastases were associated with more frequent use of this therapy sequence. Most patients received T-DM1 after treatment with pertuzumab. Both novel therapies (PH and T-DM1) are utilized in a high proportion of HER2-positive breast cancer patients. As most patients receive T-DM1 after PH, real-world data may help to clarify whether the efficacy of this sequence is similar to that in the approval study.
CRIS-Team Scopus Importer:2019-05-14
Keywords: Advanced breast cancer; Antihormone therapy; Chemotherapy; Her2 c-ERBB2; Her2/neu; Lapatinib; Metastatic; Pertuzumab; T-DM1; Trastuzumab

Therapy of early breast cancer: current status and perspectives - Tauber, Nikolas; Amann, Niklas; Dannehl, Dominik; Deutsch, Thomas M.; Dimpfl, Moritz; Fasching, Peter; Hartkopf, Andreas; Heublein, Sabine; Hilmer, Lisbeth; Hörner, Manuel; Krawczyk, Natalia; Krückel, Annika; et al. (Archives of Gynecology and Obstetrics, 2025)
Medical advancements in breast cancer are truly remarkable. Especially in recent years, numerous new therapeutics have been approved and surgical strategies have been de-escalated for specific patient groups. In the therapeutic setting, CDK4/6 inhibitors as oral maintenance therapy in early breast cancer and immune checkpoint inhibitors (Pembrolizumab) for triple-negative breast cancer (BC) are noteworthy. In the surgical field, prospective randomized controlled trials have currently explored the possibility to deescalate axillary surgery by omitting sentinel lymph node excision (INSEMA, SOUND). As a result, there have been significant improvements in prognosis and a reduction in surgical morbidity for patients. Many exciting trials are underway, and it remains to be seen whether antibody–drug conjugates beyond trastuzumab emtansine, will find their way into the treatment lines for early-stage BC. Furthermore, the integration of artificial intelligence in both diagnostics and treatment recommendation evaluation is a promising area with great potential.
CRIS-Team Scopus Importer:2025-05-02
Keywords: Early breast cancer; Future perspectives; HER2-positive; Hormone-receptor positive; Surgical de-escalation; Triple-negative

Therapy response and prognosis of patients with early breast cancer with low positivity for hormone receptors – An analysis of 2765 patients from neoadjuvant clinical trials - Villegas, Sonia L.; Nekljudova, Valentina; Pfarr, Nicole; Engel, Jutta; Untch, Michael; Schrodi, Simone; Holms, Frank; Ulmer, Hans U.; Fasching, Peter; Weber, Karsten E.; Albig, Christian; Heinrichs, Clemens; et al. (European Journal of Cancer, 2021)
Aim: To evaluate HER2-negative breast cancer (BC) with a low hormone receptor (HR) expression, with regard to pathological complete response (pCR) and survival, in comparison to triple-negative BC (TNBC) and strong HR-positive BC. Methods: We compared negative [oestrogen (ER) and progesterone receptor (PR) <1%], low-positive (ER and/or PR 1–9%) and strong-positive (ER or PR 10–100%) HR-expression in neoadjuvant clinical trial cohorts (n = 2765) of BC patients. End-points were disease-free survival (DFS), distant-disease free survival (DDFS) and overall survival (OS). We performed RNA sequencing on available tumour tissue samples from patients with low-HR expression (n = 38). Results: Ninety-four (3.4%) patients had low HR-positive tumours, 1769 (64.0%) had strong HR-positive tumours, and 902 (32.6%) had TNBC. There were no significant differences in pCR rates between women with low HR-positive tumours (27.7%) and women with TNBC (35.5%). DFS and DDFS were also not different [for DFS, hazard ratio 1.26, 95%-CI (confidence interval) : 0.87–1.83, log-rank test p = 0.951; for DDFS, hazard ratio 1.17, 95%-CI: 0.78–1.76, log-rank test p = 0.774]. Patients with strong HR-positive tumours had a significantly lower pCR rate (pCR 9.4%; odds ratio 0.38, 95%-CI: 0.23–0.63), but better DFS (hazard ratio 0.48, 95%-CI: 0.33–0.70) and DDFS (hazard ratio 0.49, 95%-CI: 0.33–0.74) than patients with low HR-positive tumours. Molecular subtyping (RNA sequencing) of low HR-positive tumours classified these predominantly into a basal subtype (86.8%). Conclusion: Low HR-positive, HER2-negative tumours have a similar clinical behaviour to TNBC showing high pCR rates and poor survival and also a basal-like gene expression signature. Patients with low HR-positive tumours should be regarded as candidates for therapy strategies targeting TNBC.
CRIS-Team Scopus Importer:2021-03-26
Keywords: Breast cancer; Breast neoplasms; Cancer biomarkers; ER-negative PR-negative HER2-negative breast cancer; Hormone-dependent neoplasms; Mammary cancer; Neoadjuvant therapy; Oestrogen receptors; Progesterone receptors; Triple-negative breast cancer

The role of peroxisome proliferator-activated receptors in endometriosis - Psilopatis, Iason; Theocharis, Stamatios; Beckmann, Matthias (Frontiers in Medicine, 2024)
Endometriosis constitutes the most common cause of chronic pelvic pain in female patients and is associated with infertility. Although there is no known cause for the disease, it is a heritable condition that is determined by numerous genetic, epigenetic, and environmental aspects. Peroxisome proliferator-activated receptors (PPARs) represent nuclear receptor proteins that control gene expression. By using the MEDLINE and LIVIVO databases we conducted a literature review in order to look into the role of PPARs in the endometriosis pathophysiology and succeeded in revealing 36 pertinent publications between 2001 and 2022. In regards to PPAR expression in endometriosis, PPARγ seems to represent the most studied PPAR isoform in endometriosis and to influence various pathways involved in the disease onset and progression. It's interesting to note that diverse treatment agents targeting the PPAR system have been identified as innovative, effective therapeutic alternatives in the context of endometriosis treatment. In conclusion, PPARs appear to contribute an important role in both endometriosis pathophysiology and therapy.
CRIS-Team Scopus Importer:2024-05-24
Keywords: endometriosis; epigenetics; inflammation; peroxisome proliferator-activated receptors; vascularization

The safety and satisfaction of ovarian tissue cryopreservation in prepubertal and adolescent girls - Lotz, Laura; Barbosa, Patricia Reis; Knorr, Christian; Hofbeck, Louisa; Hoffmann, Inge; Beckmann, Matthias; Antoniadis, Sophia; Dittrich, Ralf (Reproductive Biomedicine Online, 2020)
Research question: Is ovarian tissue cryopreservation (OTC) for fertility preservation in prepubertal and adolescent girls safe, and who would benefit most from the procedure? Design: Survey and retrospective study including patients who had OTC under the age of 18 years in a single centre for fertility preservation. Serum anti-Müllerian hormone levels were measured as a marker for detection of diminished ovarian reserve. Results: Fifty-three from 102 women participated in the survey (12 deceased, 19 declined, 17 unreachable, 1 palliative). The average age at OTC was 14.8 ± 2.3 (range: 6–17) years and at survey 21.9 ± 4.3 (range: 16–33) years. Ovarian tissue retrieval (laparoscopy: n = 45, laparotomy: n = 8) was without complications in 52 cases. In 23 (53.5%) of the 43 women who were post-menarchal at OTC, transient amenorrhoea occurred. At survey, 15 women reported a regular menstrual cycle, 25 used oral contraceptives, 9 women reported hormone replacement therapy due to primary ovary insufficiency and 4 had amenorrhoea. Two patients reported the birth of a healthy child after IVF, while 51 patients are still childless, mostly due to their young age (mean: 21.2 years). To date, one patient has had transplantation of the ovarian tissue (17 years at cryopreservation). Forty-nine of the interviewees would again decide on OTC, while three argued against it on the basis of the previous financial cost; one woman was unsure. Conclusions: Children with cancer may be at risk for gonadal insufficiency. OTC is practically the only technique that can be offered to young girls. The procedure is safe and well accepted.
CRIS-Team Scopus Importer:2020-03-27
Keywords: Adolescent females; Cancer; Fertility preservation; Ovarian tissue cryopreservation; Ovarian tissue transplantation; Prepubertal females

The SNP rs6500843 in 16p13.3 is associated with survival specifically among chemotherapy-treated breast cancer patients - Fagerholm, Rainer; Schmidt, Marjanka K.; Khan, Sofia; Rafiq, Sajjad; Tapper, William; Aittomaki, Kristiina; Greco, Dario; Heikkinen, Tuomas; Muranen, Taru A.; Fasching, Peter; Janni, Wolfgang; Weinshilboum, Richard; et al. (Oncotarget, 2015)
We have utilized a two-stage study design to search for SNPs associated with the survival of breast cancer patients treated with adjuvant chemotherapy. Our initial GWS data set consisted of 805 Finnish breast cancer cases (360 treated with adjuvant chemotherapy). The top 39 SNPs from this stage were analyzed in three independent data sets: iCOGS (n=6720 chemotherapy-treated cases), SUCCESS-A (n=3596), and POSH (n=518). Two SNPs were successfully validated: rs6500843 (any chemotherapy; per-allele HR 1.16, 95% C.I. 1.08-1.26, p=0.0001, p(adjusted)=0.0091), and rs11155012 (anthracycline therapy; per-allele HR 1.21, 95% C.I. 1.08-1.35, p=0.0010, p(adjusted)=0.0270). The SNP rs6500843 was found to specifically interact with adjuvant chemotherapy, independently of standard prognostic markers (p(interaction)=0.0009), with the rs6500843-GG genotype corresponding to the highest hazard among chemotherapy-treated cases (HR 1.47, 95% C.I. 1.20-1.80). Upon trans-eQTL analysis of public microarray data, the rs6500843 locus was found to associate with the expression of a group of genes involved in cell cycle control, notably AURKA, the expression of which also exhibited differential prognostic value between chemotherapy-treated and untreated cases in our analysis of microarray data. Based on previously published information, we propose that the eQTL genes may be connected to the rs6500843 locus via a RBFOX1-FOXM1 -mediated regulatory pathway.
EVALuna2:17642

The UGT1A6_19_GG genotype is a breast cancer risk factor - Justenhoven, Christina; Obazee, Ofure; Winter, Stefan; Rabstein, Sylvia; Lotz, Anne; Harth, Volker; Pesch, Beate; Brüning, Thomas; Baisch, Christian; Hartikainen, Jaana M.; Mannermaa, Arto; Kosma, Veli Matti; et al. (Frontiers in Genetics, 2013)
Validation of an association between the UGT1A6_19_T>G (rs6759892) polymorphism and overall breast cancer risk. A pilot study included two population-based case-control studies from Germany (MARIE-GENICA). An independent validation study comprised four independent breast cancer case-control studies from Finland (KBCP, OBCS), Germany (BBCC), and Sweden (SASBAC). The pooled analysis included 7418 cases and 8720 controls from all six studies. Participants were of European descent. Genotyping was done by MALDI-TOF MS and statistical analysis was performed by logistic regression adjusted for age and study. The increased overall breast cancer risk for women with the UGT1A6_19_GG genotype which was observed in the pilot study was confirmed in the set of four independent study collections (OR 1.13, 95% CI 1.05-1.22; p = 0.001). The pooled study showed a similar effect (OR 1.09, 95% CI 1.04-1.14; p = 0.001). The risk effect on the basis of allele frequencies was highly significant, the pooled analysis showed an OR of 1.11 (95% CI 1.06-1.16; p = 5.8 × 10-6). We confirmed the association of UGT1A6_19_GG with increased overall breast cancer risk and conclude that our result from a well powered multi-stage study adds a novel candidate to the panel of validated breast cancer susceptibility loci. © 2013 Justenhoven, Obazee, Winter, Rabstein, Lotz, Harth, Pesch, Brüning, Baisch, Hartikainen, Mannermaa, Kosma, Kataja, Winqvist, Pylkäs, Jukkola-Vuorinen, Grip, Fasching, Beckmann, Ekici, Hein, Hall, Li, Chang-Claude, Flesch-Janys, Seibold, Rudolph, Hamann, Ko and Brauch.
CRIS-Team Scopus Importer:2021-07-19
Keywords: Breast cancer risk; Metabolism; Polymorphism; UGT1A6; Validation

The Use of Assisted Reproductive Technology by European Childhood Cancer Survivors - Borgmann-Staudt, Anja; Michael, Simon; Sommerhaeuser, Greta; Fernandez-Gonzalez, Marta-Julia; Friedrich, Lucia Alacan; Klco-Brosius, Stephanie; Kepak, Tomas; Kruseova, Jarmila; Michel, Gisela; Panasiuk, Anna; Schmidt, Sandrin; Lotz, Laura; et al. (Current Oncology, 2022)
CCS often wish to have biological children yet harbour concerns about fertility impairment, pregnancy risks and the general health risks of prospective offspring. To clarify these concerns, health outcomes in survivor offspring born following ART (n = 74, 4.5%) or after spontaneous conception (n = 1585) were assessed in our European offspring study by descriptive and bivariate analysis. Outcomes were compared to a sibling offspring cohort (n = 387) in a 4:1 matched-pair analysis (n = 1681). (i) Survivors were more likely to employ ART than their siblings (4.5% vs. 3.7%, p = 0.501). Successful pregnancies were achieved after a median of one cycle with, most commonly, intracytoplasmic sperm injection (ICSI) using non-cryopreserved oocytes/sperm. (ii) Multiple-sibling births (p < 0.001, 29.7% vs. 2.5%), low birth weight (p < 0.001; OR = 3.035, 95%-CI = 1.615–5.706), and preterm birth (p < 0.001; OR = 2.499, 95%-CI = 1.401–4.459) occurred significantly more often in survivor offspring following ART utilisation than in spontaneously conceived children. ART did not increase the prevalence of childhood cancer, congenital malformations or heart defects. (iii) These outcomes had similar prevalences in the sibling population. In our explorative study, we could not detect an influence on health outcomes when known confounders, such as multiple births, were taken into account.
CRIS-Team Scopus Importer:2022-09-09
Keywords: ART; cancer; childhood and adolescence; health outcome; offspring; survivor

The use of PAMG-1 testing in patients with preterm labor, intact membranes and a short sonographic cervix reduces the rate of unnecessary antenatal glucocorticoid administration - Kehl, Sven; Weiss, Christel; Pretscher, Jutta; Baier, Friederike; Faschingbauer, Florian; Beckmann, Matthias; Stumpfe, Florian (Journal of Perinatal Medicine, 2021)
Objectives: To assess the frequency of antenatal corticosteroid (ACS) administration in cases with shortened cervical length by addition of placental alpha-microglobulin-1 (PAMG-1) testing to sonographic examination. Methods: Single centre retrospective cohort study. Rate of ACS administration was compared between cases with cervical length between 15 and 25 mm and cases with positive PAMG-1 testing and cervical length between 15 and 25 mm. We evaluated the following outcome parameters: Rate of ACS administration, gestational age at delivery, time to delivery, delivery within seven days, delivery <34 and <37 weeks' gestation, rate of admission to neonatal intensive care unit (NICU). Results: In total, 130 cases were included. "PAMG-1 group" consisted of 68 women, 62 cases built the "historical control group". ACS administration was performed less frequently in the "PAMG-1 cohort" (18 (26%) vs. 46 (74%); p<0.001). The rate of delivery within seven days did not differ (2 (3%) vs. 4 (6.5%); p=0.4239). The rates of delivery <34 weeks' gestation (7 (10%) vs. 9 (15%); p=0.4643) and <37 weeks' gestation (19 (28%) vs. 26 (42%); p=0.0939) did not differ. Time to delivery interval was longer in the PAMG-1 group (61.5 vs. 43 days, p=0.0117). NICU admission occurred more often in the "historical control group" (22 (38%) vs. 28 (60%); p=0.0272). Conclusions: Addition of biomarker testing can help to avoid unnecessary ACS administrations in women with shortened cervical length.
CRIS-Team WoS Importer:2021-12-03

The villoglandular Adenocarcinoma of the Cervix as a Tumor Model. A Literature Analysis - Dietl, Anna; Aumann, K.; Beckmann, Matthias (GEBURTSHILFE UND FRAUENHEILKUNDE, 2020)
CRIS-Team WoS Importer:2020-10-30

The WERA cancer center matrix: Strategic management of patient access to precision oncology in a large and mostly rural area of Germany - Krebs, Markus; Haller, Florian; Spörl, Silvia; Gerhard-Hartmann, Elena; Utpatel, Kirsten; Maurus, Katja; Kunzmann, Volker; Chatterjee, Manik; Venkataramani, Vivek; Maatouk, Imad; Bittrich, Max; Einwag, Tatjana; et al. (European Journal of Cancer, 2024)
Purpose: Providing patient access to precision oncology (PO) is a major challenge of clinical oncologists. Here, we provide an easily transferable model from strategic management science to assess the outreach of a cancer center. Methods: As members of the German WERA alliance, the cancer centers in Würzburg, Erlangen, Regensburg and Augsburg merged care data regarding their geographical impact. Specifically, we examined the provenance of patients from WERA´s molecular tumor boards (MTBs) between 2020 and 2022 (n = 2243). As second dimension, we added the provenance of patients receiving general cancer care by WERA. Clustering our catchment area along these two dimensions set up a four-quadrant matrix consisting of postal code areas with referrals towards WERA. These areas were re-identified on a map of the Federal State of Bavaria. Results: The WERA matrix overlooked an active screening area of 821 postal code areas – representing about 50 % of Bavaria´s spatial expansion and more than six million inhabitants. The WERA matrix identified regions successfully connected to our outreach structures in terms of subsidiarity – with general cancer care mainly performed locally but PO performed in collaboration with WERA. We also detected postal code areas with a potential PO backlog – characterized by high levels of cancer care performed by WERA and low levels or no MTB representation. Conclusions: The WERA matrix provided a transparent portfolio of postal code areas, which helped assessing the geographical impact of our PO program. We believe that its intuitive principle can easily be transferred to other cancer centers.
CRIS-Team Scopus Importer:2024-06-14
Keywords: Cancer care facilities; Community health services; Health services administration; Healthcare disparities; Intersectoral collaboration; Tertiary healthcare

TILGen: A Program to Investigate Immune Targets in Breast Cancer Patients - First Results on the Influence of Tumor-Infiltrating Lymphocytes - Würfel, Franziska; Erber, Ramona; Hübner, Hanna; Hein, Alexander; Lux, Michael P.; Jud, Sebastian; Kremer, Anita; Kranich, Hannah; Mackensen, Andreas; Häberle, Lothar; Hack, Carolin; Rauh, Claudia; et al. (Breast Care, 2018)
Background: Despite advancements in the treatment of primary and metastatic breast cancer, many patients lack a durable response to these treatments. Patients with triplenegative breast cancer (TNBC) and human epidermal growth factor receptor 2(HER2)-positive breast cancer who do not have a pathological complete response (pCR) after neoadjuvant chemotherapy (NACT) have a very poor prognosis. Tumor-infiltrating lymphocytes (TILs) have been identified as a predictive marker for pCR after NACT in TNBC and HER2-positive breast cancer. These patient populations could also be suitable for novel treatment strategies including neoepitope-based therapies. This work analyses the effect of TILs on the pCR in neoadjuvantly treated patients in the TILGen study and presents the procedures aimed at establishing neoepitope-based therapies in this study. Methods: Neoadjuvantly treated HER2positive and TNBC patients were eligible for the presented analysis concerning the association between TILs and pCR. A total of 146 patients could be identified within the TILGen study. TILs were evaluated as percentage of stromal tumor tissue in core biopsies at primary diagnosis. The phenotype 'lymphocyte-predominant breast cancer' (LPBC) was associated with pCR by logistic regression adjusted for estrogen receptor status, progesterone receptor status, HER2 status, age at diagnosis, and grading. Results: LPBC was seen in 24 (16.4%) patients. In this patient group, 66.7% achieved a pCR, while the pCR rate was 32.8% in patients with a low TIL count. The adjusted odds ratio was 6.60 (95% confidence interval 2.02-21.56; p < 0.01). Conclusion: TILs are a strong predictor of pCR in TNBC and HER2-positive breast cancer patients. Implications for the use of this information including the effect on prognosis might help to identify patients most likely to benefit from a neoepitope-based therapy approach. (C) 2018 S. Karger GmbH, Freiburg
EVALuna2:34061
Keywords: Tumor-infiltrating lymphocytes; Response; Neoadjuvant chemotherapy; TILGen study

TILGen study-immunological targets in patients with breast cancer : Influence of tumor-infiltrating lymphocytes - Erber, Ramona; Hartmann, Arndt; Beckmann, Matthias; Mackensen, Andreas; Kremer, Anita; Reimann, Hannah; Hübner, Hanna; Hein, Alexander; Lux, Michael P.; Jud, Sebastian; Häberle, Lothar; Gaß, Paul; et al. (Pathologe, 2018)
BACKGROUND: The interaction of our immune system with breast cancer (BC) cells prompted the investigation of tumor-infiltrating lymphocytes (TILs) and targeted, tumor antigen-specific immunotherapy. OBJECTIVES: Correlation between TILs and pathological complete response (pCR) after neoadjuvant systemic therapy (NACT). Tumor-specific antigens (TSAs) in HER2+ and triple negative BC and establishment of TSA-specific therapies within the interdisciplinary TILGen study. METHODS: Illustration of the TILGen study design. Assessment of TILs and correlation with pCR within this BC study. RESULTS: pCR was achieved in 38.4% (56/146) and associated with estrogen receptor/progesterone receptor negative (ER-/PR-) and HER2+ tumors. Lymphocytic predominant BC (LPBC) was found in 16.4% (24/146), particularly in ER-/PR- (ER-: 27.3% vs. ER+: 9.9%, PR-: 22.3% vs. PR+: 8.2%), large, and poorly differentiated BC. TILs were significantly correlated with pCR in multivariate analysis. In LPBC, pCR was achieved in 66.7%, whereas it was 32.8% in non-LPBC. CONCLUSIONS: First results confirm the influence of the human immune system on the response to NACT in HER2+ and triple negative BC. TSA-specific immunotherapy might improve the outcome in BC patients but there is an urgent need for comprehensive studies to further investigate this issue.
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Time and Resources Needed to Document Patients with Breast Cancer from Primary Diagnosis to Follow-up - Results of a Single-center Study - Lux, Michael P.; Sell, C. S.; Fasching, Peter; Seidl-Ertel, Janine; Bani, Mayada; Schrauder, M. G.; Jud, Sebastian; Löhberg, Christian; Rauh, C.; Hartmann, Arndt; Schulz-Wendtland, Rüdiger; Strnad, Vratislav; et al. (Geburtshilfe und Frauenheilkunde, 2014)
Aim: Certification of breast centers helps improve the quality of care but requires additional resources, particularly for documentation. There are currently no published data on the actual staff costs and financial resources required for such documentation. The aim of this study was to determine the time and resources required to document a patient with primary breast cancer from diagnosis to the end of follow-up, to establish a database for future strategic decisions. Material and Methods: All diagnostic and therapeutic procedures of patients with primary breast cancer were recorded at the University Breast Center of Franconia. All time points for documentation were evaluated using structured interviews. The times required to document a representative number of patients were determined and combined with the staff costs of the different professional groups, to calculate the financial resources required for documentation. Results: A total of 494 time points for documentation were identified. The study also identified 21 departments and 20 different professional groups involved in the documentation. The majority (54 %) of documentation was done by physicians. 62 % of all documentation involved outpatients. The results of different scenarios for the diagnosis, therapy and follow-up of breast cancer patients in a certified breast center showed that the time required for documentation can be as much as 105 hours, costing EUR 4135. Conclusion: This analysis shows the substantial staffing and financial costs required for documentation in certified centers. A multi-center study will be carried out to compare the costs for certified breast centers of varying sizes with the costs of non-certified care facilities.
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Timing of sequential use of double-balloon catheter and oral misoprostol for induction of labor - Kehl, Sven; Böhm, Lea; Weiss, Christel; Heimrich, Jutta; Dammer, Ulf; Baier, Friederike; Suetterlin, Marc; Beckmann, Matthias; Faschingbauer, Florian (Journal of Obstetrics and Gynaecology Research, 2016)
AIM: The best time to commence cervical ripening with a balloon catheter is unknown. The aim of this study was to evaluate whether application of a balloon catheter in the morning or in the evening is better when sequential prostaglandin application is planned. METHODS: This multicenter historical cohort study included 415 women with an unfavorable cervix undergoing labor induction at term. Labor was induced with a double-balloon catheter and the sequential use of oral misoprostol if necessary. The balloon catheter was placed in the morning group between 02:00-15:00 and in the evening group between 15:00-02:00. The primary outcome measure was the cesarean section rate. Secondary outcome measures included failed labor induction (no vaginal delivery within 72 h). RESULTS: The cesarean section rate did not differ between the groups (morning 26.9%, evening 24.3%; P = 0.5553); however, more women in the morning group did not deliver within 72 h (8.8% vs 3.1%; P = 0.0138). In nulliparous women, labor induction failed more often in the morning group (12% vs. 4%, P = 0.043). In parous women, the induction-to-delivery interval was longer in the morning group (1756 vs. 1349 min; P = 0.046), and there were fewer deliveries within 24 h (35% vs. 56%, P = 0.016). CONCLUSIONS: When sequential use of a double-balloon catheter and oral misoprostol for labor induction is planned, the preferable time for catheter placement is in the evening. This resulted in fewer failed inductions in nulliparous women and a shorter induction-to-delivery interval and more deliveries within 24 h in parous women.
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Tomosynthese - Schulz-Wendtland, Rüdiger; Beckmann, Matthias; Fasching, Peter; Uder, Michael (Chirurgische Praxis, 2016)
Full field digital mammography (FFDM) is the most important method for early diagnosis of breast cancer. The typical overlapping of normal and pathological tissue during the standard 2D projection, however, often reduces the specificity and sensitivity of the mammographic investigation. Digital breast tomosynthesis (DBT) provides on the basis of a limited number of single images with different projection angles not superimposed tomograms and may remove the unwanted masking by superimposed structures. Clinical studies show that the digital tomosynthesis has the real potential to reduce the recall rate and simultaneously increase the cancer detection rate, especially in women with dense breasts (detection and volumetry). The use of tomosynthesis seems to be superior to full field digital mammography in mammography screening. Other possibilities of the tomosynthesis are the dual energy mammography, contrast medium-enhanced mammography and intervention.
CRIS-Team Scopus Importer:2023-03-08
Keywords: Contrast medium-enhanced mammography; Dual energy mammography; Full-field digital mammography; Intervention; Mammography screening; Tomosynthesis

Total laparoscopic hysterectomy: how does training for surgeons in a standardized operation affect hospitals and patients? - Hildebrandt, Thomas; Emir, Seher; Boosz, Alexander; Beckmann, Matthias; Mueller, Andreas (Archives of Gynecology and Obstetrics, 2018)
PURPOSE: Surgical training usually means inexperienced physicians initially doing operations supervised by an experienced physician, to gain the experience and skills needed to conduct surgery independently. Various issues arise here for both hospitals and patients. Are training procedures associated with higher complication rates, blood losses, and transfusion rates? What does training in the operating room ultimately cost in terms of valuable surgical time? Do longer hospitalization periods potentially mean financial losses for the hospital under the diagnosis-related groups (DRG) system? METHODS: A retrospective analysis was carried out of data for 571 patients who underwent total laparoscopic hysterectomy (TLH) in the Department of Gynecology at the University of Erlangen from 2009 to 2012, with/without adnexectomy, due to benign indication; and of data for 255 patients who underwent the same procedures in Karlsruhe Municipal Hospital in 2013-2014. The patients were classified into two groups: those in whom surgery was carried out by experienced specialists who had carried out at least 40 independent operations; and those in whom it was carried out by a trainee resident who had personally done fewer than 40 operations. RESULTS: In the two groups, the patients had similar mean body mass indexes, uterus weights, and blood losses. Patients in the specialist group were slightly older. There were no differences in complication rates. Over two-thirds of complications occurred in patients with previous surgery. Procedures by residents took significantly longer. Hospitalization periods in both groups were still below the mean threshold length of stay under Germany's DRG system, so that no income losses occurred even with training procedures. CONCLUSIONS: Training and teaching operations supervised by experienced surgeons are just as safe as operations by experienced surgeons themselves. Interpretation of these data is of course limited by the retrospective study design; patients treated by specialists tended to have more prior operations and were older, with a trend toward larger uteri. Surgical training, as the example of TLH in benign indication shows here, involves an additional time of approximately 10-20 min per operation. With regard to the revenue situation, the hospitalization periods in both groups were within the profit zone for the hospital concerned.
EVALuna2:209955

Touch Imprint Cytology and Stereotactically-Guided Core Needle Biopsy of Suspicious Breast Lesions: 15-Year Follow-up - Schulz-Wendtland, Rüdiger; Fasching, Peter; Bani, Mayada; Lux, Michael P.; Jud, Sebastian; Rauh, C.; Bayer, C.; Wachter, David; Hartmann, Arndt; Beckmann, Matthias; Uder, Michael; Löhberg, Christian (Geburtshilfe und Frauenheilkunde, 2016)
Introduction: Stereotactically-guided core needle biopsies (CNB) of breast tumours allow histological examination of the tumour without surgery. Touch imprint cytology (TIC) of CNB promises to be useful in providing same-day diagnosis for counselling purposes and for planning future surgery. Having addressed the issue of accuracy of immediate microscopic evaluation of TIC, we wanted to re-examine the usefulness of this procedure in light of the present health care climate of cost containment by incorporating the surgical 15-year follow-up data and outcome. Patients and Methods: From January until December 1996 we performed TIC in core needle biopsies of 173 breast tumours in 169 patients, consisting of 122 malignant and 51 benign tumours. Histology of core needle biopsies was proven by surgical histology in all malignant and in 5 benign tumours. Surgical breast biopsy was not performed in 46 patients with 46 benign lesions, as the histological result from the core needle biopsy and the result of the TIC were in agreement with the suspected diagnosis from the complementary breast diagnostics. A 15-year follow-up of these patients followed in 2013 and follow-up data was collected from 40 women. Results: In the 15-year follow-up of the 40 benign lesions primarily confirmed using CNB and TIC, a diagnostic sensitivity, specificity, positive and negative predictive value and accuracy of 100 % was found. Conclusion: TIC and stereotactically guided CNB showed excellent long-term follow-up in patients with benign breast lesions. The use of TIC to complement CNB can therefore provide immediate cytological diagnosis of breast lesions.
EVALuna2:6752

Towards a Computable Data Corpus of Temporal Correlations between Drug Administration and Lab Value Changes - Newe, Axel; Wimmer, Stefan; Neubert, Antje; Becker, Linda; Prokosch, Hans-Ulrich; Beckmann, Matthias; Fietkau, Rainer; Forster, Christian; Neurath, Markus; Schett, Georg; Ganslandt, Thomas (PLoS ONE, 2015)
Background The analysis of electronic health records for an automated detection of adverse drug reactions is an approach to solve the problems that arise from traditional methods like spontaneous reporting or manual chart review. Algorithms addressing this task should be modeled on the criteria for a standardized case causality assessment defined by the World Health Organization. One of these criteria is the temporal relationship between drug intake and the occurrence of a reaction or a laboratory test abnormality. Appropriate data that would allow for developing or validating related algorithms is not publicly available, though. Methods In order to provide such data, retrospective routine data of drug administrations and temporally corresponding laboratory observations from a university clinic were extracted, transformed and evaluated by experts in terms of a reasonable time relationship between drug administration and lab value alteration. Result The result is a data corpus of 400 episodes of normalized laboratory parameter values in temporal context with drug administrations. Each episode has been manually classified whether it contains data that might indicate a temporal correlation between the drug administration and the change of the lab value course, whether such a change is not observable or whether a decision between those two options is not possible due to the data. In addition, each episode has been assigned a concordance value which indicates how difficult it is to assess. This is the first open data corpus of a computable ground truth of temporal correlations between drug administration and lab value alterations. Discussion The main purpose of this data corpus is the provision of data for further research and the provision of a ground truth which allows for comparing the outcome of other assessments of this data with the outcome of assessments made by human experts. It can serve as a contribution towards systematic, computerized ADR detection in retrospective data. With this lab value curve data as a basis, algorithms for detecting temporal relationships can be developed, and with the classification made by human experts, these algorithms can immediately be validated. Due to the normalization of the lab value data, it allows for a generic approach rather than for specific or solitary drug/lab value combination

Toxic effect of light on oocyte and pre-implantation embryo: a systematic review - Khodavirdilou, Rasa; Pournaghi, Marjaneh; Oghbaei, Hajar; Rezaei, Yeganeh Rastgar; Javid, Farzin; Khodavirdilou, Lida; Shakibfar, Farah; Latifi, Zeinab; Hakimi, Parvin; Nouri, Mohammad; Fattahi, Amir; Dittrich, Ralf (Archives of Toxicology, 2021)
In the female reproductive tract, oocytes and embryos are in a dark environment, while during the in vitro fertilization (IVF) they are exposed to various visible and invisible lights such as daylight, microscope, and laminar hood fluorescent lights. Studies have shown that light could damage cellular compartments of oocytes and embryos and consequently decrease rates of fertilization, development, and blastocyst formation. However, due to the lack of consensus about the effects of light on the embryos, and subsequently the inability to make definitive decisions regarding the light exposure management to improve IVF results, in the present study, we systematically reviewed the effect of light with different wavelengths and intensities on pre-implantation embryos. The toxic impact of light depends on the wavelength, intensity, and duration of light exposure and also the stage of embryo. Therefore, reducing the observation time of embryos out of the incubator and also using light filters can alleviate the detrimental effect of light in IVF labs.
CRIS-Team WoS Importer:2021-09-10

Toxicity Assessment of a Phase III Study Evaluating FEC-Doc and FEC-Doc Combined with Gemcitabine as an Adjuvant Treatment for High-Risk Early Breast Cancer: the SUCCESS-A Trial - Schroeder, L.; Rack, B.; Sommer, H.; Koch, J. G.; Weissenbacher, T.; Janni, W.; Schneeweiss, A.; Rezai, M.; Lorenz, R.; Jaeger, B.; Schramm, A.; Häberle, Lothar; et al. (Geburtshilfe und Frauenheilkunde, 2016)
Introduction: This paper aims to evaluate the toxicity profile of additive gemcitabine to adjuvant taxane-based chemotherapy in breast cancer patients.Methods:Patients enrolled in this open-label randomized controlled Phase III study were treated with 3 cycles of epirubicin-fluorouracil-cyclophosphamide (FEC) chemotherapy followed by 3 cycles of docetaxel with those receiving 3 cycles of FEC followed by 3 cycles of gemcitabine-docetaxel (FEC-DG). 3690 patients were evaluated according to National Cancer Institute (NCI) toxicity criteria (CTCAE). The study medications were assessed by the occurrence of grade 3-4 adverse events, dose reductions, postponements of treatment cycles and granulocyte colony-stimulating factor (G-CSF) support.Results:No differences in neutropenia or febrile neutropenia were demonstrated. However, thrombocytopenia was significantly increased with FEC-DG treatment (2.0 vs. 0.5 %, p < 0.001), as was leukopenia (64.1 vs. 58.5 %, p < 0.001). With FEC-DG significantly more G-CSF support in cycles 4 to 6 (FEC-DG: 57.8 %, FEC-D: 36.3 %, p < 0.001) was provided. Transaminase elevation was significantly more common with FEC-DG (SGPT: 6.3 %, SGOT: 2 %), whereas neuropathy (1.2 %), arthralgia (1.6 %) and bone pain (2.6 %) were more common using FEC-D. Dose reductions > 20 % (4 vs. 2.4 %) and postponement of treatment cycles (0.9 vs. 0.4 %) were significantly more frequent in the FEC-DG arm. Eight deaths occurred during treatment in the FEC-DG arm and four in the FEC-D arm.Conclusion:The addition of gemcitabine increased hematological toxicity and was associated with more dose reductions and postponements of treatment cycles.
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TP53-based interaction analysis identifies cis-eQTL variants for TP53BP2, FBXO28, and FAM53A that associate with survival and treatment outcome in breast cancer - Fagerholm, Rainer; Khan, Sofia; Schmidt, Marjanka K.; Garcia-Closas, Montserrat; Heikkila, Pavi; Saarela, Jani; Beesley, Jonathan; Jamshidi, Maral; Aittomaki, Kristiina; Liu, Jianjun; Ali, H. Raza; Andrulis, Irene L.; et al. (Oncotarget, 2017)
TP53 overexpression is indicative of somatic TP53 mutations and associates with aggressive tumors and poor prognosis in breast cancer. We utilized a two-stage SNP association study to detect variants associated with breast cancer survival in a TP53-dependent manner. Initially, a genome-wide study (n = 575 cases) was conducted to discover candidate SNPs for genotyping and validation in the Breast Cancer Association Consortium (BCAC). The SNPs were then tested for interaction with tumor TP53 status (n = 4,610) and anthracycline treatment (n = 17,828). For SNPs interacting with anthracycline treatment, siRNA knockdown experiments were carried out to validate candidate genes.In the test for interaction between SNP genotype and TP53 status, we identified one locus, represented by rs10916264 (p(interaction) = 3.44 × 10-5; FDR-adjusted p = 0.0011) in estrogen receptor (ER) positive cases. The rs10916264 AA genotype associated with worse survival among cases with ER-positive, TP53-positive tumors (hazard ratio [HR] 2.36, 95% confidence interval [C.I] 1.45 - 3.82). This is a cis-eQTL locus for FBXO28 and TP53BP2; expression levels of these genes were associated with patient survival specifically in ER-positive, TP53-mutated tumors. Additionally, the SNP rs798755 was associated with survival in interaction with anthracycline treatment (p(interaction) = 9.57 × 10-5, FDR-adjusted p = 0.0130). RNAi-based depletion of a predicted regulatory target gene, FAM53A, indicated that this gene can modulate doxorubicin sensitivity in breast cancer cell lines.If confirmed in independent data sets, these results may be of clinical relevance in the development of prognostic and predictive marker panels for breast cancer.
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Transcriptome-wide association study of breast cancer risk by estrogen-receptor status - Feng, Helian; Gusev, Alexander; Pasaniuc, Bogdan; Wu, Lang; Long, Jirong; Abu-Full, Zomoroda; Aittomaki, Kristiina; Andrulis, Irene L.; Anton-Culver, Hoda; Antoniou, Antonis C.; Arason, Adalgeir; Arndt, Volker; et al. (Genetic Epidemiology, 2020)
Previous transcriptome-wide association studies (TWAS) have identified breast cancer risk genes by integrating data from expression quantitative loci and genome-wide association studies (GWAS), but analyses of breast cancer subtype-specific associations have been limited. In this study, we conducted a TWAS using gene expression data from GTEx and summary statistics from the hitherto largest GWAS meta-analysis conducted for breast cancer overall, and by estrogen receptor subtypes (ER+ and ER−). We further compared associations with ER+ and ER− subtypes, using a case-only TWAS approach. We also conducted multigene conditional analyses in regions with multiple TWAS associations. Two genes, STXBP4 and HIST2H2BA, were specifically associated with ER+ but not with ER– breast cancer. We further identified 30 TWAS-significant genes associated with overall breast cancer risk, including four that were not identified in previous studies. Conditional analyses identified single independent breast-cancer gene in three of six regions harboring multiple TWAS-significant genes. Our study provides new information on breast cancer genetics and biology, particularly about genomic differences between ER+ and ER− breast cancer.
CRIS-Team Scopus Importer:2020-03-20
Keywords: breast cancer subtype; causal gene; GWAS; TWAS

Translational Highlights in Breast and Ovarian Cancer 2019 – Immunotherapy, DNA Repair, PI3K Inhibition and CDK4/6 Therapy - Hartkopf, Andreas D.; Mueller, Volkmar; Woeckel, Achim; Lux, Michael P.; Janni, Wolfgang; Ettl, Johannes; Belleville, Erik; Schuetz, Florian; Fasching, Peter; Kolberg, Hans-Christian; Welslau, Manfred; Overkamp, Friedrich; et al. (Geburtshilfe und Frauenheilkunde, 2019)
In the near future, important translational questions of clinical relevance will be adressed by studies currently in progress. On the one hand, the role of PD-L1 expression must be further understood, after it was found to be relevant in the use of atezolizumab in first-line therapy of patients with metastatic triple-negative breast cancer (TNBC). No association between efficacy and PD-L1 expression was found in a neoadjuvant study that included pembrolizumab in TNBC. The pathological complete response rate (pCR) was higher in both patient groups with and without PD-L1 expression when pembrolizumab was added to chemotherapy. Another future question is the identification of further patient groups in which efficacy of PARP inhibitors is seen, which are licensed for the pBRCA1/2 germline mutation. These include, for example, patients with mutations in other genes, which are involved in homologous recombination, or patients with tumours that show an abnormality in global tests of homologous recombination deficiencies (HRD tests). The question of whether a PARP inhibitor can be given and with which chemotherapy combination partners is currently being investigated in both breast and ovarian cancer. While the data on improved overall survival are being consolidated for the CDK4/6 inhibitors, knowledge of molecular changes during the therapy and during progression on the therapy is growing. Both the accumulation of PI3K mutations and also PTEN changes might play a part in planning subsequent therapies. This review article summarises these recent developments in breast cancer and in part also in ovarian cancer.
CRIS-Team WoS Importer:2020-01-17

Translational highlights in breast cancer research and treatment: recent developments with clinical impact - Fasching, Peter; Schneeweiss, Andreas; Kolberg, Hans-Christian; Ettl, Johannes; Fehm, Tanja N.; Overkamp, Friedrich; Lueftner, Diana (Current Opinion in Obstetrics & Gynecology, 2019)
Purpose of review Over the last decades the time which is needed to translate a preclinical finding or idea in the clinic has reduced continuously. Especially but not only for breast cancer the number of tested drugs and targeted pathways have increased immensely. In addition, the introduction of immune-oncological treatments has further advanced the possibilities for future treatments. This review focuses on recent developments in the prevention and treatment of breast cancer including results from major clinical trials and recent conferences. Recent findings Many pathways involved in the progression or treatment of breast cancer have been also identified in the cause and pathogenesis of breast cancer. Therefore, breast cancer risk can be described in much more detail, possibly leading to new prevention strategies. In breast cancer treatment the introduction of PARP inhibitors has begun. Recent trials will lead to a better understanding whether PI3K inhibitors can be developed for application in the clinic and first large randomized trials show the superiority of anti PD-1/PD-L1 treatments. Treatment strategies which were developed over the last decade are moving rapidly into the clinical use. The understanding of treatment targets and involved side effects will be important for the safe implementation of these treatments into routine practice.
CRIS-Team WoS Importer:2019-04-12

Transplantation of ovarian tissue to postpone menopause - is it really more advantageous for women's health than menopause hormone therapy? - Von Wolff, Michael; Dittrich, Ralf; Stute, Petra (Reproductive Biomedicine Online, 2015)
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Transplantation of refreezed ovarian tissue after unexpected occurrence of endometriosis - Dietl, Anna; Dittrich, Ralf; Hoffmann, Inge; Denschlag, D.; Hanjalic-Beck, A.; Mueller, A.; Beckmann, Matthias; Lotz, Laura (GEBURTSHILFE UND FRAUENHEILKUNDE, 2022)
CRIS-Team WoS Importer:2022-11-04

Trastuzumab Biosimilars in the Therapy of Breast Cancer – “Real World” Experiences from four Bavarian University Breast Centres - Hester, Anna; Gaß, Paul; Fasching, Peter; Kraemer, Anne Katrin; Ettl, Johannes; Diessner, Joachim; Woeckel, Achim; Egger, Tobias; Stock, Katja; Redlin, Jutta; Andraschko, Monika; Harbeck, Nadia; et al. (Geburtshilfe und Frauenheilkunde, 2020)
Introduction With the introduction of the first trastuzumab biosimilar in the summer of 2018, biosimilar antibodies for breast cancer have found their way into the area of gynaecological oncology. The switch of anti-human epidermal growth factor receptor 2 (HER2) therapy from the reference drug Herceptin ® to a biosimilar has presented challenges to the clinics. In addition to structural and organisational measures, training of employees as well as patient briefing and acceptance were major challenges. The study presented here records - within the context of quality assurance - how the switch to a trastuzumab biosimilar was implemented at four Bavarian university clinics in the Purchasing Association of Bavarian University Pharmacies. Materials/Methods Questionnaires on treatment figures and the switching process were sent to breast centres and pharmacies of four Bavarian university clinics between July and December 2019. The neoadjuvant, adjuvant and metastasised anti-HER2 therapy with trastuzumab with or without pertuzumab was recorded, evaluated and summarised. Results In the anti-HER2-therapy, trastuzumab was used intravenously (i. v.) and subcutaneously. Between July and December 2018, all four clinics in the Purchasing Association switched the i. v. trastuzumab therapy from the reference drug (Herceptin) to a biosimilar (for 2018: Kanjinti ®). Over 200 patients were treated with trastuzumab i. v. in each of the two half-years of 2018 (before and after the switch). The spectrum of side effects and pCR rates under therapy with the biosimilar were comparable to the experiences made with the reference drug. Three out of four clinics provided training to employees and informed patients by means of a defined information leaflet. Patient acceptance was high. Summary The anti-HER2 therapy could be switched successfully and safely to trastuzumab biosimilars at the Bavarian university hospitals. This may serve as guideline for the further implementation of biosimilars. The structures necessary for this initial switching process have been prepared with trastuzumab as an example.
CRIS-Team Scopus Importer:2020-12-18
Keywords: biosimilar; breast cancer; HER2; pCR; trastuzumab

Trastuzumab Emtansine for Residual Invasive HER2-Positive Breast Cancer - Von Minckwitz, G.; Huang, C. -S.; Mano, M. S.; Loibl, S.; Mamounas, E. P.; Untch, M.; Wolmark, N.; Rastogi, P.; Schneeweiss, A.; Redondo, A.; Fischer, H. H.; Jacot, W.; et al. (New England Journal of Medicine, 2019)
BACKGROUND
CRIS-Team WoS Importer:2019-02-27

Trastuzumab versus observation for HER2 nonamplified early breast cancer with circulating tumor cells (EORTC 90091-10093, BIG 1-12, Treat CTC): a randomized phase II trial - Ignatiadis, M.; Litiere, S.; Rothe, F.; Riethdorf, S.; Proudhon, C.; Fehma, T.; Aalders, K.; Forstbauer, H.; Fasching, Peter; Brain, E.; Vuylsteke, P.; Guardiola, E.; et al. (Annals of Oncology, 2018)
Trastuzumab improves the outcome of women with HER2 positive breast cancer. We aimed to assess whether trastuzumab decreases the detection rate of circulating tumor cells (CTCs) in women with high risk, HER2 nonamplified, early breast cancer.The EORTC 90091-10093 BIG 1-12 Treat CTC is a phase II trial, conducted in 70 hospitals and 6 CTC laboratories across 5 European countries. Patients with centrally confirmed HER2 nonamplified breast cancer and >=1 centrally confirmed CTC per 15 ml of blood by CellSearch® following surgery and (neo)adjuvant chemotherapy were randomized (1 : 1) to 6 cycles of trastuzumab intravenously versus 18 weeks of observation. Randomization was stratified for center, locally confirmed estrogen receptor status and adjuvant versus neoadjuvant chemotherapy. The primary end point was rate of detection of >=1 CTC per 15 ml of blood at week 18. Secondary end points were invasive disease-free survival (iDFS) and cardiac safety.Between 30 April 2013 and 17 October 2016, 1317 patients were screened; 95 (7.2%) had detectable CTC(s), and 63 (4.8%) were randomized to trastuzumab (n = 31) or observation (n = 32). Fifty-eight patients were assessable for the primary end point, 29 in each arm. In 9 of the 58 patients, CTC(s) were still detected at week 18 : 5 in the trastuzumab and 4 in the observation arm (one-sided Fisher's exact test, P = 0.765). An Independent Data Monitoring Committee recommended stopping further accrual for futility for the primary end point. Median follow-up at database lock was 13 months (IQR 4-16.5). The 1-year iDFS was 93.8% (95% CI 77.3-98.4) in the observation versus 84.8% (95% CI 63.4-94.2) in the trastuzumab arm. No grade 2-4 cardiac events were observed in the trastuzumab arm.Trastuzumab does not decrease the detection rate of CTCs in HER2 nonamplified, nonmetastatic breast cancer.
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Treatment and outcomes of patients in the Brain Metastases in Breast Cancer Network Registry - Witzel, I.; Laakmann, E.; Weide, R.; Neunhoeffer, T.; Park-Simon, T. -J.; Schmidt, Marcus; Fasching, Peter; Hesse, T.; Polasik, A.; Mohrmann, S.; Wuerschmidt, F.; Schem, C.; et al. (European Journal of Cancer, 2018)
Brain metastases (BMs) have a major impact on life expectancy and quality of life for many breast cancer patients. Knowledge about treatment patterns and outcomes is limited.We analysed clinical data of 1712 patients diagnosed with BMs from breast cancer between January 2000 and December 2016 at 80 institutions.Median age at diagnosis of BMs was 56 years (22-90 years). About 47.8% (n = 732) of patients had HER2-positive, 21.4% (n = 328) had triple-negative and 30.8% (n = 471) had hormone receptor (HR)-positive, HER2-negative (luminal-like) primary tumours. The proportion of patients with HER2-positive BMs decreased comparing the years 2000-2009 with 2010-2015 (51%-44%), whereas the percentage of patients with luminal-like tumours increased (28%-34%; p = 0.0331). Patients with BMs in the posterior fossa were more often HER2 positive (n = 169/314, 53.8%) than those diagnosed with triple-negative (n = 65/314, 20.7%) or luminal-like primary breast cancer (n = 80/314, 25.5%), (p < 0.0001). Median overall survival (OS) time after development of BMs for the overall cohort was 7.4 months (95% confidence interval [CI]: 6.7-8.0 months). One-year survival rate was 37.7% (95% CI: 35.2-40.1). Patients with HER2-positive tumours had the longest median OS of 11.6 months (95% CI: 10.0-13.4) compared with 5.9 months (95% CI: 5.0-7.2) for patients with luminal-like and 4.6 months (95% CI: 3.9-5.4) for patients with triple-negative tumours. Patients with HER2-positive tumours who received anti-HER2 treatment had longer median OS than those without (17.1 months versus 7.2 months, p < 0.0001).Prognosis of patients after developing BMs varies significantly according to the subtype. The outcome in this cohort is similarly poor in triple-negative and HR-positive/HER2-negative patients. Our results underline the high medical need for improvement of treatment and prevention strategies for BMs in breast cancer patients.
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Treatment landscape and prognosis after treatment with trastuzumab emtansine - Laakmann, Elena; Emons, Julius; Taran, Florin Andrei; Janni, Wolfgang; Uhrig, Sabrina; Overkamp, Friedrich; Kolberg, Hans Christian; Hadji, Peyman; Tesch, Hans; Häberle, Lothar; Ettl, Johannes; Lüftner, Diana; et al. (Geburtshilfe und Frauenheilkunde, 2020)
Purpose Pertuzumab and T-DM1 are two efficient anti-HER2 treatments for patients with HER2-positive advanced breast cancer. While pertuzumab is usually given in first-line treatment and T-DM1 in second-line treatment, standard therapy options seem to be exhausted up to now after the treatment of patients with these two therapy options. Therefore, it is important to have data that describes the therapy situation and prognosis after T-DM1 treatment. Methods The PRAEGNANT metastatic breast cancer registry (NCT02338167) is a prospective registry for breast cancer patients with a focus on molecular biomarkers. Patients of all therapy lines with any kind of treatment are eligible. Collected data comprises therapies, adverse events, quality of life and other patient reported outcomes. Here we report on the patient characteristics and descriptive prognostic data for HER2-positive patients who have completed a treatment with T-DM1. Therapy patterns after T-DM1 and progression-free survival are reported as well as overall survival. Results A total of 85 patients were identified for the study who were prospectively observed during therapy after the termination of T-DM1. The main reason for T-DM1 termination was progress. Following T-DM1, lapatinib, trastuzumab and chemotherapy were the main therapy choices. Median progression-free survival was 4.8 months (95% CI: 3.2-6.3) and median overall survival was 18.4 months (95% CI: 15.5-21.3). Conclusions Therapy options after T-DM1 in a real-world setting seem to exhibit a relevant clinical efficacy, supporting the concept of continuous anti-HER2 treatments in the advanced therapy setting for breast cancer patients. Novel therapies are needed to improve the rather short median progression-free survival.
CRIS-Team Scopus Importer:2020-11-20
Keywords: advanced breast cancer; antihormone therapy; chemotherapy; HER2 c-erbB2; HER2/neu; lapatinib; metastatic; pertuzumab; T-DM1; trastuzumab

Treatment landscape of advanced breast cancer patients with hormone receptor positive HER2 negative tumors - Data from the German PRAEGNANT breast cancer registry - Hartkopf, Andreas D.; Huober, Jens; Volz, Bernhard; Nabieva, Naiba; Taran, Florin-Andrei; Schwitulla, Judith; Overkamp, Friedrich; Kolberg, Hans-Christian; Hadji, Peyman; Tesch, Hans; Häberle, Lothar; Ettl, Johannes; et al. (BREAST, 2018)
PURPOSE: This study describes comprehensive data from a breast cancer registry concerning the use of endocrine treatment (ET) and chemotherapy in the first, second and higher therapy lines in hormone receptor (HR) positive, HER2 negative metastatic breast cancer (MBC). METHODS: The PRAEGNANT study is a real-time registry for patients with MBC. Therapies were categorized into the following categories: chemotherapy, aromatase inhibitor (AI), tamoxifen, fulvestrant, or everolimus plus ET and reported for first, second and third line or higher therapy use. Also treatment sequences for the first, second and third therapy line were analyzed. RESULTS: This analysis includes 958 patients with HR positive, HER2 negative MBC. 42.7% were treated with a chemotherapy in the first therapy line compared to 45.9% receiving an ET. A total of 25.9% were treated with everolimus plus anti-hormone therapy in any therapy line. 34.1% were treated with fulvestrant as single agent therapy. Analyzing therapy sequences, the administration of three different chemotherapies in a row was the most frequently used pattern. CONCLUSIONS: This analysis shows that across all three first therapy lines chemotherapy is a dominant therapy for HR positive, HER2 negative MBC patients. Education about the efficacy of ET might help to increase its use and decrease the possible burden of chemotherapy related toxicities.
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Treatment of Early Breast Cancer Patients: Evidence, Controversies, Consensus: Focusing on Systemic Therapy - German Experts' Opinions for the 16th International St. Gallen Consensus Conference (Vienna 2019) - Lüftner, Diana; Bauerfeind, Ingo; Braun, Michael; Brucker, Sara Y.; Fasching, Peter; Felberbaum, Ricardo; Hagemann, Friederike; Haidinger, Renate; Harbeck, Nadia; Hönig, Arnd; Huober, Jens; Jackisch, Christian; et al. (Breast Care, 2019)
A German working group of leading breast cancer experts have discussed the votes at the International St. Gallen Consensus Conference in Vienna for the treatment of primary breast cancer with regard to the German AGO (Ar-beitsgemeinschaft Gynäkologische Onkologie) recommendations for clinical practice in Germany. Three of the German breast cancer experts were also members of this year's St. Gallen panel. Comparing the St. Gallen recommendations with the annually updated treatment recommendations of the Gynecological Oncology Working Group (AGO Mamma 2019) and the German S3 Guideline is useful, because the recommendations of the St. Gallen panel are based on expert opinions of different countries and disciplines. The focus of this article is on systemic therapy. The motto of this year's 16th St. Gallen Consensus Conference was "Estimating the magnitude of clinical benefit." The rationale behind this motto is that, for every treatment decision, a benefit-risk assessment must be taken into consideration for each patient.
CRIS-Team Scopus Importer:2019-10-01

Treatment of Early Breast Cancer The 18th St. Gallen International Breast Cancer Consensus Conference against the Background of Current German Treatment Recommendations Behandlung des frühen Mammakarzinoms 18. Internationaler St.-Gallen-Konsens vor dem Hintergrund der aktuellen deutschen Therapieempfehlungen diskutiert - Untch, Michael; Banys-Paluchowski, Maggie; Brucker, Sara Y.; Budach, Wilfried; Denkert, Carsten; Ditsch, Nina; Fasching, Peter; Haidinger, Renate; Heil, Jörg; Jackisch, Christian; Janni, Wolfgang; Kolberg, Hans Christian; et al. (Geburtshilfe und Frauenheilkunde, 2023)
This year's 18th St. Gallen (SG) consensus conference on the treatment of early breast cancer (SGBCC: St. Gallen International Breast Cancer Conference) focused on practice-oriented questions. The individual situation and risk-benefit assessment were discussed in great detail. As in previous years, a German working group of leading breast cancer experts presented the results of the international SGBCC 2023 against the background of German treatment recommendations – especially the updated treatment recommendations of the Arbeitsgemeinschaft Gynäkologische Onkologie e.V. (AGO) – for everyday clinical practice in Germany. The German treatment recommendations of AGO are based on the current evidence. The comparison with the clinical approach in Germany has proven useful, as the SGBCC panel consists of experts from different countries and disciplines. That is why country-specific characteristics can be incorporated into the SGBCC recommendations.
CRIS-Team Scopus Importer:2024-12-16
Keywords: (neo)adjuvant systemic therapy; early-onset breast cancer; genetics; pathology; radiotherapy; St. Gallen Consensus 2023; surgery

Treatment of Patients with Early Breast Cancer: Evidence, Controversies, Consensus: German Expert Opinions on the 17th International St. Gallen Consensus Conference - Untch, Michael; Fasching, Peter; Brucker, Sara Y.; Budach, Wilfried; Denkert, Carsten; Haidinger, Renate; Huober, Jens; Jackisch, Christian; Janni, Wolfgang; Kolberg-Liedtke, Cornelia; Krug, David; Kuehn, Thorsten; et al. (Geburtshilfe und Frauenheilkunde, 2021)
This years 17th St. Gallen (SG) Consensus Conference on the Treatment of Patients with Early Breast Cancer (SG-BCC) with the title "Customizing local and systemic therapies for women with early breast cancer" focused on the challenge of targeting the treatment of early breast cancer more specifically to the individual disease situation of each patient. As in previous years, a German working group of leading breast cancer experts discussed the results of the international SG-BCC 2021 in the context of the German guideline. It is helpful to compare the SG recommendations with the recently updated treatment recommendations of the Breast Commission of the German Working Group on Gynaecological Oncology (Arbeitsgemeinschaft Gynakologische Onkologie e.V., AGO) and the S3 guideline because the SG-BCC panel comprised experts from different countries, which is why country-specific aspects can be incorporated into the SG recommendations. The German treatment recommendations of the AGO and the S3 guideline are based on current evidence. Nevertheless, any therapeutic decision must always undergo a risk-benefit analysis for the specific situation and to be discussed with the patient.
CRIS-Team WoS Importer:2021-06-18

Treatment-related amenorrhea with T-DM1 plus pertuzumab (KP) is lower than with docetaxel/carboplatin/ trastuzumab/pertuzumab (TCHP) in the phase III neoadjuvant KRISTINE trial - Hurvitz, Sara A.; Fresco, Rodrigo; Afenjar, Karen; Stroyakovskiy, Daniil; Huang, Chiun-Sheng; Wildiers, Hans; Jung, Kyung Hae; Boileau, Jean-Francois; Campone, Mario; Martin, Miguel; Valero, Vicente; Sparano, Joseph A.; et al. (CANCER RESEARCH, 2021)
CRIS-Team WoS Importer:2021-03-26

Treatment-relevant biomarkers in gynecologic oncology - Ditsch, Nina; Fasching, Peter (Die Gynäkologie, 2022)
The first biomarkers were discovered decades ago. Their prognostic and predictive value is still the subject of current research. Biomarker-based treatments represent the basis of the current and future trial landscape in gynecologic oncology, as was clearly demonstrated at this year's ASCO Annual Meeting. The all-important question is founded in the quality of diagnostics at the immunohistochemical or molecular level. In breast cancer therapy, a HER-2 (human epidermal growth factor receptor 2) finding was previously considered therapeutically relevant if there was an immunohistochemical (IHC) evaluation of 3+ or a fluorescence in situ hybridization (FISH)- or chromogenic in situ hybridization (CISH)-positive value. Use of the antibody-drug conjugate trastuzumab-deruxtecan, also in HER-2-low forms (IHC1+ or 2+, even if FISH/CISH negative), is now celebrated as practice changing, since significantly improved progression-free survival (PFS) and overall survival (OS) were also shown in this situation. With the accelerating use of newer therapeutics, attention should be paid to the side effects and the cost-benefit ratio. The following article provides an overview of the currently most important prognostic and predictive markers in breast, ovarian, endometrial, and cervical cancer.
CRIS-Team WoS Importer:2022-09-09

Treatment with ribociclib shows favourable immunomodulatory effects in patients with hormone receptor-positive breast cancer—findings from the RIBECCA trial - Peuker, Caroline A.; Yaghobramzi, Sarvenaz; Grunert, Corinna; Keilholz, Luisa; Gjerga, Enio; Hennig, Steffen; Schaper, Sigrid; Na, Il Kang; Keller, Ulrich; Brucker, Sara; Decker, Thomas; Fasching, Peter; et al. (European Journal of Cancer, 2022)
Background: Inhibitors of the cyclin-dependent kinases 4 and 6 (CDK4/6i) have significantly improved clinical outcomes in patients with advanced hormone receptor-positive (HR+) breast cancer and have demonstrated favourable antitumour immune responses in preclinical studies. Methods: Here, we investigated peripheral immune responses to ribociclib in patients with metastatic HR+ breast cancer as a preplanned exploratory subanalysis of the RIBECCA trial (NCT03096847). Peripheral blood mononuclear cells were subjected to immune cell profiling, gene expression analysis of immune-related signatures, and deep T cell receptor profiling before treatment started and after 12 weeks of treatment with ribociclib. Results: Gene expression analysis revealed an upregulation of signatures associated with an activated adaptive immune system and a decrease in immunosuppressive cytokine signalling during treatment with ribociclib. Profiling of peripheral immune cell subpopulations showed a decrease in Treg cell frequencies, which was associated with treatment response. Furthermore, induction of CD4+ naive T cells could be seen, whereas effector and memory T cell populations remained largely unchanged. Correspondingly, T cell repertoire diversity remained mostly unchanged during treatment, although an increase in clonality could be observed in single patients. Conclusions: We show that treatment with ribociclib has significant effects on the peripheral innate and adaptive immune response in patients with HR+ breast cancer. Our data suggest that these effects lead to an activation of an already existing immune response rather than a de novo induction and make a strong case for future combination strategies of CDK4/6i with immunotherapies to enhance the adaptive immune response in HR+ breast cancer.
CRIS-Team Scopus Importer:2022-02-11
Keywords: Adaptive immunity; Breast cancer; CDK4/6 inhibitors; Immunomodulation; Ribociclib

Trial of labor after caesarean section in low risk pregnancies: is it risky? - Kehl, Sven; Düster, Hanna; Weiss, Christel; Bader, Simon; Schneider, Michael; Beckmann, Matthias; Dammer, Ulf; Pretscher, Jutta (Archives of Gynecology and Obstetrics, 2024)
Purpose: To evaluate the influence of a previous caesarean section on adverse composite maternal and perinatal outcome in women who attempted a trial of labor. Methods: This historical cohort study analyzed maternal and perinatal outcome in women with otherwise low risk pregnancies at term who underwent a trial of labor after a caesarean section (TOLAC). The primary outcome measure was the adverse composite outcome. Secondary outcome measures were amongst others the caesarean section rate and the mode of vaginal delivery. Results: The adverse composite outcome was more frequently in the previous caesarean section group compared to women with no previous caesarean Sect. (22.3% vs. 15.6%, p < 0.0001). The percentage of caesarean Sect. (15.4% vs. 8.2%, p < 0,0001), uterine rupture (1.0% vs. 0.02%, p < 0.0001), placental abruption (1.1% vs. 0.3%, p = 0.0014), vaginal operative delivery (16.0% vs. 8.6%, p < 0.0001), pH < 7.10 (3.7% vs. 2.5%, p = 0.0151), base excess < -12 (3.2% vs. 2.2%, p = 0.0297), abnormal cardiotocography (22.5% vs. 13.9%, p < 0,0001) and fetal blood analysis (6.2% vs. 2.6%, p < 0.0001) was significantly higher in women with a previous caesarean section. Taking the parity into account, these differences could only been seen in women without a previous vaginal delivery. In parous women with a previous vaginal delivery and a caesarean section in history, the adverse composite did not differ between the groups. Only the rate of pH < 7.1 was higher in women after a caesarean Sect. (4.5% vs. 1.8%, p = 0.0436). Conclusion: Trial of labor after caesarean in otherwise low risk pregnancies is associated with a higher rate of complications especially if there is no history of vaginal delivery.
CRIS-Team Scopus Importer:2024-09-06
Keywords: Caesarean section rate; Composite adverse outcome; Prior caesarean section; TOLAC; Uterine rupture; VBAC

Triple-Negative Breast Cancer Risk Genes Identified by Multigene Hereditary Cancer Panel Testing - Shimelis, Hermela; Laduca, Holly; Hu, Chunling; Hart, Steven N.; Na, Jie; Thomas, Abigail; Akinhanmi, Margaret; Moore, Raymond M.; Brauch, Hiltrud; Cox, Angela; Eccles, Diana M.; Ewart-Toland, Amanda; et al. (Journal of the National Cancer Institute, 2018)
BACKGROUND: Germline genetic testing with hereditary cancer gene panels can identify women at increased risk of breast cancer. However, those at increased risk of triple-negative (estrogen receptor-negative, progesterone receptor-negative, human epidermal growth factor receptor-negative) breast cancer (TNBC) cannot be identified because predisposition genes for TNBC, other than BRCA1, have not been established. The aim of this study was to define the cancer panel genes associated with increased risk of TNBC. METHODS: Multigene panel testing for 21 genes in 8753 TNBC patients was performed by a clinical testing laboratory, and testing for 17 genes in 2148 patients was conducted by a Triple Negative Breast Cancer Consortium (TNBCC) of research studies. Associations between deleterious mutations in cancer predisposition genes and TNBC were evaluated using results from TNBC patients and reference controls. RESULTS: Germline pathogenic variants in BARD1, BRCA1, BRCA2, PALB2, and RAD51D were associated with high risk (odds ratio > 5.0) of TNBC and greater than 20% lifetime risk for overall breast cancer among Caucasians. Pathogenic variants in BRIP1, RAD51C, and TP53 were associated with moderate risk (odds ratio > 2) of TNBC. Similar trends were observed for the African American population. Pathogenic variants in these TNBC genes were detected in 12.0% (3.7% non-BRCA1/2) of all participants. CONCLUSIONS: Multigene hereditary cancer panel testing can identify women with elevated risk of TNBC due to mutations in BARD1, BRCA1, BRCA2, PALB2, and RAD51D. These women can potentially benefit from improved screening, risk management, and cancer prevention strategies. Patients with mutations may also benefit from specific targeted therapeutic strategies.
EVALuna2:210020

Trophoblast expression dynamics of the tumor suppressor gene gastrokine 2 - Fahlbusch, Fabian B.; Ruebner, Matthias; Hübner, Hanna; Volkert, Gudrun; Bartunik, Hannah; Winterfeld, Ilona; Hartner, Andrea; Menendez-Castro, Carlos; Nögel, Stephanie; Marek, Ines; Wachter, David; Schneider-Stock, Regine; et al. (Histochemistry and Cell Biology, 2015)
Gastrokines (GKNs) were originally described as stomach-specific tumor suppressor genes. Recently, we identified GKN1 in extravillous trophoblasts (EVT) of human placenta. GKN1 treatment reduced the migration of the trophoblast cell line JEG-3. GKN2 is known to inhibit the proliferation, migration and invasion of gastric cancer cells and may interact with GKN1. Recently, GKN2 was detected in the placental yolk sac of mice. We therefore aimed to further characterize placental GKN2 expression. By immunohistochemistry, healthy first-trimester placenta showed ubiquitous staining for GKN2 at its early gestational stage. At later gestational stages, a more differentiated expression pattern in EVT and villous cytotrophoblasts became evident. In healthy third-trimester placenta, only EVT retained strong GKN2 immunoreactivity. In contrast, HELLP placentas showed a tendency of increased levels of GKN2 expression with a more prominent GKN2 staining in their syncytiotrophoblast. Choriocarcinoma cell lines did not express GKN2. Besides its trophoblastic expression, we found human GKN2 in fibrotic villi, in amniotic membrane and umbilical cord. GKN2 co-localized with smooth muscle actin in villous myofibroblasts and with HLA-G and GKN1 in EVT. In the rodent placenta, GKN2 was specifically located in the spongiotrophoblast layer. Thus, the gestational age-dependent and compartment-specific expression pattern of GKN2 points to a role for placental development. The syncytial expression of GKN2 in HELLP placentas might represent a reduced state of functional differentiation of the syncytiotrophoblast. Moreover, the specific GKN2 expression in the rodent spongiotrophoblast layer (equivalent to human EVT) might suggest an important role in EVT physiology.
EVALuna2:6725