Qualitätssicherungsrichtlinie Früh- und Reifgeborene des Gemeinsamen Bundesausschusses als Qualitätsrisiko? Analyse zu Erfüllungsgrad und Konsequenzen in der Versorgung weiterer intensivpflichtiger Patienten sowie drohender Frühgeburten am Beispiel eines regionalen Verbund-Perinatalzentrums - Kleeberg, Markus; Beckmann, Matthias; Fusch, Christoph; Hanf, Volker; Kainer, Franz; Klinge, Jens; Koehler, Wolfgang; Morhart, Patrick; Schroth, Michael Andreas (Zeitschrift für Geburtshilfe und Neonatologie, 2020)
Background The quality guideline for care delivery to preterm and mature infants (QFR-RL) places high demands on perinatal centers. In this analysis, the degree of fulfillment was determined. Additionally, care delivery to further patient groups and sufficient nursing staff capacity for caredelivery to imminent preterm infants (FG) were evaluated. Methods A network of 4 perinatal centers (level 1) with about 10,000 births per year supplied the data on the ratio of 1:1/1:2-care infants,patients per nurse, and nursing staff capacity. This data was statistically evaluated by center, shift, and week day over a period of 5 months for compliance with QFR-RL and DGPM recommendations. Furthermore, imminent preterm infants were recorded and compared with available nursing staff capacity. Results In total, the QFR-RL was fulfilled in 88% of shifts (n=1,584). Only one center reached the required 95. The degree of fulfillment and the number of staff nurses declined from late to night shifts (p<0.001). The ratio of 1:1-care infants was significantly higher when demands were not fulfilled (p<0.001). Only 14.1 of imminent preterm infants could have been attended in accordance with the QFR-RL. Conclusion 1:1 care as well as lower nurse staffing in late and night shifts lead to non-fulfillment of requirements and poorer care delivery to other intensive care patients. This was also reflected in the lower degree of fulfillment of DGPM recommendations. Sufficient nursing staff capacity was rare with the consequence that it was almost impossible to deliver care to imminent preterm infants per the guideline.
CRIS-Team Scopus Importer:2020-11-06
Keywords: 1:1-Care; preterm infants care; quality guideline of care delivery of preterm and mature infants; quality of care; staffing ratio

Quality-adjusted survival with ribociclib plus fulvestrant (R plus F) versus placebo plus fulvestrant (P plus F) in postmenopausal women (PMW) HR+/HER2-advanced breast cancer (ABC) based on the MONALEESA-3 trial - Jerusalem, G.; Delea, T.; Martin Jimenez, M.; De Laurentiis, M.; Nusch, A.; Beck, J. T.; Chan, A.; Im, S-A.; Neven, P.; Lonshteyn, A.; Chandiwana, D.; Lanoue, B.; et al. (ANNALS OF ONCOLOGY, 2020)
CRIS-Team WoS Importer:2020-06-26

Quality-Adjusted Survival with Ribociclib Plus Fulvestrant Versus Placebo Plus Fulvestrant in Postmenopausal Women with HR±HER2− Advanced Breast Cancer in the MONALEESA-3 Trial - Jerusalem, Guy; Delea, Thomas E.; Martin, Migule; De Laurentiis, Michelino; Nusch, Arnd; Beck, J. Thaddeus; Chan, Arlene; Im, Seock Ah; Neven, Patrick; Lonshteyn, Alexander; Chandiwana, David; Lanoue, Brad; et al. (Clinical Breast Cancer, 2022)
Background: MONALEESA-3 demonstrated an overall survival (OS) benefit for ribociclib plus fulvestrant (R+F) in postmenopausal women with hormone receptor (HR) positive, HER2 negative advanced breast cancer (ABC). This study estimated quality-adjusted (QA) survival outcomes for patients receiving R+F vs. placebo (P)+F in MONALEESA-3. Methods: Kaplan-Meier OS was partitioned into health states: (1) toxicity (TOX)=time spent with grade 3 –4 adverse events before progression (DP); (2) progression (PROG)=time between DP and death; and (3) time without symptoms or toxicity (TWiST)=time not in TOX or PROG. QA time was calculated by combining estimated mean time in each health state with treatment-group specific health-state utility values estimated using EQ-5D-5L questionnaire. Outcomes included QA progression-free survival (QAPFS), QAOS, and QA TWiST (Q-TWiST). Q-TWiST was calculated with health-state utility values for TOX and PROG defined relative to TWiST. Results: Mean PFS and OS were significantly greater with R+F vs. P+F (difference 0.56 and 0.19 years). Mean time in TOX and TWiST were greater with R+F; mean time in PROG was greater with P+F. QAPFS was 0.45 years (95% CI 0.27 –0.63) greater with R+F than P+F (P <.001). QAOS was numerically greater with R+F vs. P+F (0.16 years, 95% CI 0.07 –0.45, P = .0569). Q-TWiST was 0.23 years greater with R+F (95% CI 0.07 –0.45, P = .0069). In a sensitivity analysis using an estimate of disutility for PROG, the difference in QAOS was 0.23 years (95% CI 0.08 –0.41, P = .0022). Conclusion: R+F in postmenopausal women with HR+/HER2- ABC improves QAPFS, resulting in clinically important improvements in Q-TWiST and may improve QAOS.
CRIS-Team Scopus Importer:2022-01-28
Keywords: Breast cancer; Fulvestrant; Postmenopausal; Quality of life; Ribociclib; Survival

Quality assurance and improvement in oncology using guideline-derived quality indicators - results of gynaecological cancer centres certified by the German cancer society (DKG) - Griesshammer, Ellen; Wesselmann, S.; Beckmann, Matthias; Dannecker, C.; Wagner, U.; Sibert, N. T.; Armbrust, R.; Sehouli, J. (Journal of Cancer Research and Clinical Oncology, 2022)
Purpose Based on the example of Gynaecological Cancer Centres (GCCs) certified by the German Cancer Society, this study evaluates the results of medical-guideline-derived quality indicators (QIs) for cervical cancer (CC) and ovarian cancer (OC), examines the development of indicator implementation over time as well as the status of guideline-compliant care and identifies improvement measures. Methods QI results for patients with CC and OC treated in GCCs between 2015 and 2019 are analysed. The median, overall proportion and standard deviation of each QI were calculated. Two-sided Cochran-Armitage tests were applied. Results QIs are divided into two categories: process-organization (PO-QIs) and treatment-procedures (TP-QIs), to allow a differentiated analysis for identifying improvement measures. PO-QIs that reflect the implementation of processes and structures show a high degree of application. PO-QIs have a tremendous influence on the quality of care and are easy to implement through SOPs. TP-QIs report on treatments that are performed in the GCC. TP-QIs that report on systemic therapies reach a plateau where the guideline is known, but patient-related-factors meaningfully prevent further increase. TP-QIs that report on surgical interventions fluctuate. The most relevant factors are practitioners' personal skills. Besides the discussion of results amongst peers during the audit, improvement measures could include surgical courses or coaching. Conclusion The analysis shows that a combination of different measures is necessary to anchor quality sustainably in health care and thus improve it.
CRIS-Team WoS Importer:2022-06-17
Keywords: Quality indicators; Quality assurance; Health service research; Certification

Quality of life and oncological outcome in endometrial cancer patients after vaginal brachytherapy: comparison of two dosing schemes - Papathemelis, Thomas; Scharl, Sophia; Hipp, Matthias; Scharl, Anton; Beckmann, Matthias; Lux, Michael P.; Koelbl, Oliver (Archives of Gynecology and Obstetrics, 2019)
Purpose: Vaginal brachytherapy reduces the risk of local recurrence and was shown to be equieffective in preventing vaginal vault recurrence, but less toxic compared to external-beam radiotherapy in a subset of high intermediate-risk endometrial cancer patients and is administered as single adjuvant treatment in those patients. Different radiotherapeutic approaches with various dosing schemes exist toward brachytherapy. The aim of this study was to compare the outcome and long-term quality of life after brachytherapy with two different high-dose-rate dosing schemes. Methods: Retrospective analysis was conducted of the recurrence and survival rates of 104 patients with endometrial cancer FIGO stage I–II that underwent adjuvant brachytherapy with three times 5 Gy or four times 5 Gy to the upper two-thirds of the vaginal vault in two different institutions between January 2010 and December 2013. Quality of life was assessed by EORTC QLQ-30 questionnaire and EN 24 module. Results: The vaginal vault recurrence rates were 4.9% and 5.0% for patients treated with 3 × 5 Gy and 4 × 5 Gy, respectively (p = 0.98). We did not observe a difference in pelvic recurrence (p = 0.96), overall survival (p = 0.33) or quality of life between the different radiotherapy regimens. Metastatic recurrence and the use of chemotherapy contribute to impairment on quality of life. Younger patients (< 70 years) reported worse emotional functioning (p = 0.02) and higher symptom scales of diarrhea (p = 0.01) and financial problems (p = 0.03). Sexual activity was lower in patients younger than 70 years (p = 0.05). Conclusions: Further prospective studies are needed to evaluate the effect of dosing schemes on recurrence rates and quality of life. Younger patients (< 70 years) seem to experience greater reduction in quality of life due to endometrial cancer diagnosis.
CRIS-Team Scopus Importer:2019-05-21
Keywords: Adjuvant treatment; Brachytherapy; Endometrial cancer; Radiotherapy

Quality of Life and Treatment-Related Side Effects in Patients With HR+/HER2- Advanced Breast Cancer: Findings From a Multicountry Survey - Cardoso, Fatima; Rihani, Julie; Harmer, Victoria; Harbeck, Nadia; Casas, Ana; Rugo, Hope S.; Fasching, Peter; Moore, Adam; de Courcy, Joanna; Pathak, Purnima; Haftchenary, Sina; Aubel, Dawn; et al. (Oncologist, 2023)
BACKGROUND: Quality of life (QOL) is a critical factor in decision-making for advanced breast cancer (ABC). There is a need to improve how QOL and treatment-related side effects (SEs) that impact it are clinically assessed. We examined healthcare professionals' (HCPs') and patients' perspectives on the importance of QOL discussions and the impact of SEs on QOL in clinical settings. PATIENTS AND METHODS: A cross-sectional online survey was conducted (7/2020-5/2021) among oncologists, nurses, and patients with HR+/HER2- ABC in 7 countries. RESULTS: The survey was completed by 502 HCPs and 467 patients. Overall, 88% of oncologists and 49% of patients recalled QOL discussions at follow-up. In the first- through fourth-line (1L, 2L, 3L, and 4L) settings, respectively, 48%, 57%, 79%, and 85% of oncologists reported QOL was very important; 73% and 45% of patients receiving 1L and 2L treatment and 40% receiving 3L+ treatment indicated QOL was important. Patients reported that insomnia, anxiety, back pain, fatigue, diarrhea, hot flashes, low sexual interest, and loss of appetite had a moderate/severe impact on QOL. Of patients experiencing certain SEs, ≥64% did not discuss them with HCPs until there was a moderate/severe impact on QOL. In patients receiving a CDK4/6 inhibitor, SEs, including insomnia, diarrhea, back pain, and fatigue, had a moderate/severe impact on QOL. CONCLUSIONS: This survey discovered disconnects between HCPs and patients with ABC on the importance of QOL discussions and the impact of SEs on QOL. These data support the use of ABC-specific QOL questionnaires that closely monitor SEs impacting QOL.
CRIS-Team Scopus Importer:2023-10-20
Keywords: advanced breast cancer; physician/patient communication; qualitative research; quality of life; survey

Quality of life with talazoparib after platinum or multiple cytotoxic non-platinum regimens in patients with advanced breast cancer and germline BRCA1/2 mutations: patient-reported outcomes from the ABRAZO phase 2 trial - Hurvitz, S. A.; Quek, R. G. W.; Turner, N. C.; Telli, M. L.; Rugo, H. S.; Mailliez, A.; Ettl, J.; Grischke, E.; Mina, L. A.; Balmana, Judith; Fasching, Peter; Bhattacharyya, H.; et al. (European Journal of Cancer, 2018)
BACKGROUND: Talazoparib (1 mg/day) exhibited promising efficacy and safety in patients with advanced breast cancer during ABRAZO (NCT02034916); this study evaluated patient-reported outcomes (PROs). PATIENTS AND METHODS: ABRAZO is a two-cohort, two-stage, phase 2 study of talazoparib in patients with advanced breast cancer after a response to prior platinum-based therapy (cohort 1 [C1], n = 49) or ≥3 platinum-free cytotoxic-based regimens (cohort 2 [C2], n = 35). PROs were assessed on day 1 (baseline), every 6 weeks for an initial 24 weeks, and every 12 weeks thereafter until progression, using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (QLQ-C30) and its breast cancer module, QLQ-BR23. RESULTS: Global health status/quality of life (GHS/QoL) was maintained from baseline across all time points for both C1 and C2. For C1 and C2, median time to deterioration (TTD) of GHS/QoL (95% confidence interval [CI]) was 2.8 (2.1, 3.0) and 5.5 (4.2, 5.7) months, respectively. Median TTD for all QLQ-C30 functional scales for C1 and C2 ranged 2.1-3.1 months and 4.2-5.6 months, respectively; median TTD for all QLQ-BR23 symptom scales ranged 2.6-4.0 months and 4.2-5.6 months, respectively. There were no statistically significant differences in estimated overall change from baseline in the GHS/QoL scale for both cohorts (C1: -2.6 [95% CI, -7.8, 2.5]; C2: 1.2 [95% CI, -5.5, 8.0]). Significant overall improvements in the breast symptoms and arm symptoms and the future perspective of patients in C1 and C2 were observed, despite the statistically significant and clinically meaningful overall deterioration among patients regarding their role functioning (in C1) and dyspnoea symptoms (in C2). CONCLUSION: Despite the statistically significant and clinically meaningful overall deterioration among patients regarding their role functioning (in C1) and dyspnoea symptoms (in C2), patients in both C1 and C2 reported significant overall improvements in their breast symptoms, arm symptoms and future perspective, and their GHS/QoL was maintained from baseline.
EVALuna2:202806

Quantification of thyroid volume using 3-D ultrasound imaging - Kollorz, Eva Nicole Karin; Hahn, Dieter; Linke, Rainer; Goecke, Tamme W.; Hornegger, Joachim; Kuwert, Torsten (IEEE Transactions on Medical Imaging, 2008)
Ultrasound (US) is among the most popular diagnostic techniques today. It is non-invasive, fast, comparably cheap, and does not require ionizing radiation. US is commonly used to examine the size, and structure of the thyroid gland. In clinical routine, thyroid imaging is usually performed by means of 2-D US. Conventional approaches for measuring the volume of the thyroid gland or its nodules may therefore be inaccurate due to the lack of 3-D information. This work reports a semi-automatic segmentation approach for the classification, and analysis of the thyroid gland based on 3-D US data. The images are scanned in 3-D, pre-processed, and segmented. Several pre-processing methods, and an extension of a commonly used geodesic active contour level set formulation are discussed in detail. The results obtained by this approach are compared to manual interactive segmentations by a medical expert in five representative patients. Our work proposes a novel framework for the volumetric quantification of thyroid gland lobes, which may also be expanded to other parenchymatous organs. © 2006 IEEE.

RAD51B in Familial Breast Cancer - Pelttari, Liisa M.; Khan, Sofia; Vuorela, Mikko; Kiiski, Johanna I.; Vilske, Sara; Nevanlinna, Viivi; Ranta, Salla; Schleutker, Johanna; Winqvist, Robert; Kallioniemi, Anne; Doerk, Thilo; Bogdanova, Natalia V.; et al. (PLoS ONE, 2016)
Common variation on 14q24.1, close to RAD51B, has been associated with breast cancer: rs999737 and rs2588809 with the risk of female breast cancer and rs1314913 with the risk of male breast cancer. The aim of this study was to investigate the role of RAD51B variants in breast cancer predisposition, particularly in the context of familial breast cancer in Finland. We sequenced the coding region of RAD51B in 168 Finnish breast cancer patients from the Helsinki region for identification of possible recurrent founder mutations. In addition, we studied the known rs999737, rs2588809, and rs1314913 SNPs and RAD51B haplotypes in 44,791 breast cancer cases and 43,583 controls from 40 studies participating in the Breast Cancer Association Consortium (BCAC) that were genotyped on a custom chip (iCOGS). We identified one putatively pathogenic missense mutation c.541C>T among the Finnish cancer patients and subsequently genotyped the mutation in additional breast cancer cases (n = 5259) and population controls (n = 3586) from Finland and Belarus. No significant association with breast cancer risk was seen in the meta-analysis of the Finnish datasets or in the large BCAC dataset. The association with previously identified risk variants rs999737, rs2588809, and rs1314913 was replicated among all breast cancer cases and also among familial cases in the BCAC dataset. The most significant association was observed for the haplotype carrying the risk-alleles of all the three SNPs both among all cases (odds ratio (OR): 1.15, 95% confidence interval (CI): 1.11-1.19, P = 8.88 x 10-16) and among familial cases (OR: 1.24, 95% CI: 1.16-1.32, P = 6.19 x 10-11), compared to the haplotype with the respective protective alleles. Our results suggest that loss-of-function mutations in RAD51B are rare, but common variation at the RAD51B region is significantly associated with familial breast cancer risk.
EVALuna2:33327

Randomised, open-label, phase II study comparing the efficacy and the safety of cabazitaxel versus weekly paclitaxel given as neoadjuvant treatment in patients with operable triple-negative or luminal B/HER2-negative breast cancer (GENEVIEVE) - Kuemmel, Sherko; Paepke, Stefan; Huober, Jens; Schem, Christian; Untch, Michael; Blohmer, Jens Uwe; Eiermann, Wolfgang; Gerber, Bernd; Hanusch, Claus; Hilfrich, Joern; Jackisch, Christian; Schneeweiss, Andreas; et al. (European Journal of Cancer, 2017)
BACKGROUND: The GENEVIEVE study compared the pathological complete response (pCR) rate (ypT0/is ypN0/+) in patients with operable human epidermal growth factor receptor 2 (HER2)-negative breast cancer (BC) treated with either cabazitaxel or paclitaxel. METHODS: GENEVIEVE was a prospective, multicentre, randomised, open-label, phase II study comparing the efficacy and the safety of four 3-weekly cycles cabazitaxel versus 12 weeks of paclitaxel given as neoadjuvant treatment. Primary end-point was the pCR rate defined as the complete absence of invasive carcinoma on histological examination of the breast irrespective of lymph node involvement (ypT0/is, ypN0/+) after the taxane treatment. Patients could receive an anthracycline-based therapy thereafter. RESULTS: Overall, 333 patients were randomised and started treatment with 74.7% and 83.2% of patients completing treatment in the cabazitaxel and paclitaxel arms, respectively. Patients in cabazitaxel arm had a significantly lower pCR rate compared to the paclitaxel arm (1.2% versus 10.8%; p = 0.001). A total of 42 (25.3%) patients in the cabazitaxel arm and 17 (10.2%) in the paclitaxel arm had at least one serious adverse event (p < 0.001). Dose reductions were observed in 9.6% patients in the cabazitaxel arm compared to 11.4% in the paclitaxel arm (p = 0.721). Main reason for dose reductions was non-haematological toxicities in 3.0% versus 7.8% (p = 0.087), respectively. CONCLUSIONS: The GENEVIEVE study showed no short-term effect of cabazitaxel in triple-negative or luminal B/HER2-negative primary BC, while there seemed to be no differences in drug exposure and patient compliance between the two arms. CLINICAL TRIALS REGISTRATION: ClinicalTrials.gov NCT01779479.
EVALuna2:36185

Randomized, open-label, phase II study comparing the efficacy and the safety of cabazitaxel versus weekly paclitaxel given as neoadjuvant treatment in patients with operable triple negative or luminal B/HER2 normal breast cancer (GENEVIEVE) - Paepke, S.; Huober, J.; Sherko, K.; Eidtmann, H.; Untch, M.; Costa, S. Dan; Blohmer, J. U.; Eiermann, W.; Gerber, B.; Hanusch, C.; Hilfrich, J.; Jackisch, C.; et al. (2016)
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RANK and RANKL Expression in Tumors of Patients with Early Breast Cancer - Behrens, Annika; Wurmthaler, Lena; Heindl, Felix; Gaß, Paul; Häberle, Lothar; Volz, Bernhard; Hack, Carolin; Emons, Julius; Erber, Ramona; Hartmann, Arndt; Beckmann, Matthias; Rübner, Matthias; et al. (Geburtshilfe und Frauenheilkunde, 2023)
Introduction The receptor activator of nuclear factor-κB (RANK) pathway was associated with the pathogenesis of breast cancer. Several studies attempted to link the RANK/RANKL pathway to prognosis; however, with inconsistent outcomes. We aimed to further contribute to the knowledge about RANK/RANKL as prognostic factors in breast cancer. Within this study, protein expression of RANK and its ligand, RANKL, in the tumor tissue was analyzed in association with disease-free survival (DFS) and overall survival (OS) in a study cohort of patients with early breast cancer. Patients and Methods 607 samples of female primary and early breast cancer patients from the Bavarian Breast Cancer Cases and Controls Study were analyzed to correlate the RANK and RANKL expression with DFS and OS. Therefore, expression was quantified using immunohistochemical staining of a tissue microarray. H-scores were determined with the cut-off value of 8.5 for RANK and 0 for RANKL expression, respectively. Results RANK and RANKL immunohistochemistry were assessed by H-score. Both biomarkers did not correlate (ρ = -0.04). According to molecular subtypes, triple-negative tumors and HER2-positive tumors showed a higher number of RANK-positive tumors (H-score ≥ 8.5), however, no subtype-specific expression of RANKL could be detected. Higher RANKL expression tended to correlate with a better prognosis. However, RANK and RANKL expression could not be identified as statistically significant prognostic factors within the study cohort. Conclusions Tumor-specific RANK and RANKL expressions are not applicable as prognostic factors for DFS and OS, but might be associated with subtype-specific breast cancer progression.
CRIS-Team Scopus Importer:2023-12-22
Keywords: breast cancer; immunohistochemistry; prognosis; RANK; RANKL

RANK Expression as an Independent Predictor for Response to Neoadjuvant Chemotherapy in Luminal-Like Breast Cancer: A Translational Insight from the GeparX Trial - Link, Theresa; Blohmer, Jens Uwe; Schmitt, Wolfgang D.; Kuhlmann, Jan Dominik; Just, Marianne; Untch, Michael; Stoetzer, Oliver J.; Fasching, Peter; Thill, Marc; Reinisch, Mattea; Schneeweiss, Andreas; Wimberger, Pauline; et al. (Clinical Cancer Research, 2023)
Purpose: The GeparX study investigated whether denosumab as add-on treatment to nab-paclitaxel–based neoadjuvant chemotherapy (NACT) with two different schedules (125 mg/m2 weekly vs. day 1, 8 every 22 days) may increase pathologic complete response (pCR) rate. The addition of denosumab to NACT did not improve pCR rates as recently published. In this study, we investigated whether receptor activator of nuclear factor-kappa B (RANK) expression, as part of the denosumab target pathway: (i) may retrospectively identify a subgroup of patients with additional clinical benefit of denosumab or (ii) may predict response to nab-paclitaxel NACT. Experimental Design: RANK protein was IHC-stained on pre-therapeutic core biopsies from patients of the GeparX study (n ¼ 667) with the antibody RANK/Envision System HRP (DAB) and was analyzed for the percentage of membranous RANK tumor cell staining (>5% RANKhigh vs. ≤5% RANKlow). Results: We could not identify any patient subgroup with differential response under denosumab add-on treatment in patients with RANKhigh expression [139/667, 20.8%; OR, 0.86; 95% confidence interval (CI), 0.44–1.68; P ¼ 0.667] or RANKlow expression (528/667 (79.2%) OR, 1.10; 95% CI, 0.78–1.56; P ¼ 0.589; Pinteraction ¼ 0.528). However, the pCR rate was higher in the RANKhigh subgroup compared with RANKlow (50% vs. 39%; OR, 1.52; 95% CI, 1.04–2.21; P ¼ 0.037). RANK expression constituted an independent predictor of response to NACT frequently in patients with luminal-like subtype (HRþ/HER2−; OR, 2.98; 95% CI, 1.30–6.79; P ¼ 0.010). No predictive value of RANK expression among the different nab-paclitaxel regimens was observed. Conclusion: We report RANK expression to be an independent predictive biomarker for response to NACT in patients with luminal-like breast cancer.
CRIS-Team Scopus Importer:2023-12-08

RANKL and OPG and their influence on breast volume changes during pregnancy in healthy women - Wunderle, Marius; Rübner, Matthias; Häberle, Lothar; Schwenke, Eva; Hack, Carolin; Bayer, Christian M.; Koch, Martin; Schwitulla, Judith; Schulz-Wendtland, Rüdiger; Kozieradzki, Ivona; Lux, Michael P.; Beckmann, Matthias; et al. (Scientific Reports, 2020)
Breast cancer risk is reduced by number of pregnancies and breastfeeding duration, however studies of breast changes during or after pregnancy are rare. Breast volume changes - although not linked to breast cancer risk - might be an interesting phenotype in this context for correlative studies, as changes of breast volume vary between pregnant women. Serum receptor activator of nuclear factor kappa B ligand (RANKL) and its antagonist osteoprotegerin (OPG) were measured prospectively before gestational week 12, and three-dimensional breast volume assessments were performed. A linear regression model including breast volume at the start of pregnancy, RANKL, OPG, and other factors was used to predict breast volume at term. The mean breast volume was 413 mL at gestational week 12, increasing by a mean of 99 mL up to gestational week 40. In addition to body mass index and breast volume at the beginning of pregnancy, RANKL and OPG appeared to influence breast volume with a mean increase by 32 mL (P = 0.04) and a mean reduction by 27 mL (P = 0.04), respectively. Linking the RANKL/RANK/OPG pathway with breast volume changes supports further studies aiming at analysing breast changes during pregnancy with regard to breast cancer risk.
CRIS-Team Scopus Importer:2020-03-31

Rare Case Report - Mucoepidermoid Carcinoma (MEC) of the Vulva - Dietl, Anna; Stübs, Frederik; Schulmeyer, Carla; Behrens, Annika; Hartmann, Arndt; Agaimy, Abbas; Beckmann, Matthias; Gaß, Paul (GEBURTSHILFE UND FRAUENHEILKUNDE, 2022)
CRIS-Team WoS Importer:2022-11-04

Rare germline copy number variants (CNVs) and breast cancer risk - Dennis, Joe; Tyrer, Jonathan P.; Walker, Logan C.; Michailidou, Kyriaki; Dorling, Leila; Bolla, Manjeet K.; Wang, Qin; Ahearn, Thomas U.; Andrulis, Irene L.; Anton-Culver, Hoda; Antonenkova, Natalia N.; Arndt, Volker; et al. (Communications Biology, 2022)
Germline copy number variants (CNVs) are pervasive in the human genome but potential disease associations with rare CNVs have not been comprehensively assessed in large datasets. We analysed rare CNVs in genes and non-coding regions for 86,788 breast cancer cases and 76,122 controls of European ancestry with genome-wide array data. Gene burden tests detected the strongest association for deletions in BRCA1 (P = 3.7E-18). Nine other genes were associated with a p-value < 0.01 including known susceptibility genes CHEK2 (P = 0.0008), ATM (P = 0.002) and BRCA2 (P = 0.008). Outside the known genes we detected associations with p-values < 0.001 for either overall or subtype-specific breast cancer at nine deletion regions and four duplication regions. Three of the deletion regions were in established common susceptibility loci. To the best of our knowledge, this is the first genome-wide analysis of rare CNVs in a large breast cancer case-control dataset. We detected associations with exonic deletions in established breast cancer susceptibility genes. We also detected suggestive associations with non-coding CNVs in known and novel loci with large effects sizes. Larger sample sizes will be required to reach robust levels of statistical significance.
CRIS-Team Scopus Importer:2022-02-04

Real-world effectiveness of ribociclib 1 aromatase inhibitor, or endocrine monotherapy, or chemotherapy as first-line treatment in postmenopausal women with HR-positive, HER2-negative locally advanced or metastatic breast cancer: The RIBANNA study - Fasching, Peter; Decker, T.; Guderian, G.; Heim, J.; Jackisch, C.; Lueck, H-J.; Lueftner, D.; Marme, F.; Reimer, T.; Woeckel, A. (ANNALS OF ONCOLOGY, 2018)
CRIS-Team WoS Importer:2019-03-08

Real-world efficacy of ribociclib plus aromatase inhibitor/fulvestrant, or endocrine monotherapy, or chemotherapy as first-line treatment in women with HR-positive, HER2-negative locally advanced or metastatic breast cancer: Third interim analysis from the RIBANNA study - Wockel, Achim; Brucker, Cosima; Decker, Thomas; Falbrede, Jorg; Forstbauer, Helmut; Gohler, Thomas; Hoffmann, Oliver; Jackisch, Christian; Janssen, Jan; Kohler, Andreas; Ludtke-Heckenkamp, Kerstin; Luftner, Diana; et al. (CANCER RESEARCH, 2021)
CRIS-Team WoS Importer:2021-03-26

Recommendations of the AGG (Task Force for Obstetrics, Section Maternal Diseases) on the Management of Maternal Hepatitis B, C and D Infection in Pregnancy - Kühnert, Maritta; Kehl, Sven; Pecks, Ulrich; Schäfer-Graf, Ute Margaretha; Groten, Tanja; Schild, Ralf Lothar; Schlembach, Dietmar; Schmidt, Markus; Hamza, Amr (Geburtshilfe und Frauenheilkunde, 2021)
These statements and recommendations should provide appropriate information about maternal and fetal routes of infection, screening, detection of risk factors, diagnostic procedures, treatment, birth planning and peripartum and postpartum management of maternal hepatitis infection and offer pointers for prenatal counselling and routine clinical care on delivery wards.
CRIS-Team Scopus Importer:2021-05-21
Keywords: delivery; hepatitis; pregnancy; puerperium; viral infection

Recommendations of the AGG (Working Group for Obstetrics, Department of Maternal Diseases) on How to Treat Thyroid Function Disorders in Pregnancy. - Hamza, Amr; Schlembach, Dietmar; Schild, Ralf Lothar; Groten, Tanja; Wölfle, Joachim; Battefeld, Wilgard; Kehl, Sven; Schneider, Michael (Geburtshilfe und Frauenheilkunde, 2023)
Objective These recommendations from the AGG (Committee for Obstetrics, Department of Maternal Diseases) on how to treat thyroid function disorder during pregnancy aim to improve the diagnosis and management of thyroid anomalies during pregnancy. Methods Based on the current literature, the task force members have developed the following recommendations and statements. These recommendations were adopted after a consensus by the members of the working group. Recommendations The following manuscript gives an insight into physiological and pathophysiological thyroid changes during pregnancy, recommendations for clinical and subclinical hypo- and hyperthyroidism, as well as fetal and neonatal diagnostic and management strategies.
EVALuna2:548561

Reconstructing tumor history in breast cancer: signatures of mutational processes and response to neoadjuvant chemotherapy☆ - Denkert, C.; Untch, M.; Benz, S.; Schneeweiss, A.; Weber, K. E.; Schmatloch, S.; Jackisch, C.; Sinn, H. P.; Golovato, J.; Karn, T.; Marmé, F.; Link, T.; et al. (Annals of Oncology, 2021)
Background: Different endogenous and exogenous mutational processes act over the evolutionary history of a malignant tumor, driven by abnormal DNA editing, mutagens or age-related DNA alterations, among others, to generate the specific mutational landscape of each individual tumor. The signatures of these mutational processes can be identified in large genomic datasets. We investigated the hypothesis that genomic patterns of mutational signatures are associated with the clinical behavior of breast cancer, in particular chemotherapy response and survival, with a particular focus on therapy-resistant disease. Patients and methods: Whole exome sequencing was carried out in 405 pretherapeutic samples from the prospective neoadjuvant multicenter GeparSepto study. We analyzed 11 mutational signatures including biological processes such as APOBEC-mutagenesis, homologous recombination deficiency (HRD), mismatch repair deficiency and also age-related or tobacco-induced alterations. Results: Different subgroups of breast carcinomas were defined mainly by differences in HRD-related and APOBEC-related mutational signatures and significant differences between hormone-receptor (HR)-negative and HR-positive tumors as well as correlations with age, Ki-67 and immunological parameters were observed. We could identify mutational processes that were linked to increased pathological complete response rates to neoadjuvant chemotherapy with high significance. In univariate analyses for HR-positive tumors signatures, S3 (HRD, P < 0.001) and S13 (APOBEC, P = 0.001) as well as exonic mutation rate (P = 0.002) were significantly correlated with increased pathological complete response rates. The signatures S3 (HRD, P = 0.006) and S4 (tobacco, P = 0.011) were prognostic for reduced disease-free survival of patients with chemotherapy-resistant tumors. Conclusion: The results of this investigation suggest that the clinical behavior of a tumor, in particular, response to neoadjuvant chemotherapy and disease-free survival of therapy-resistant tumors, could be predicted by the composition of mutational signatures as an indicator of the individual genomic history of a tumor. After additional validations, mutational signatures might be used to identify tumors with an increased response rate to neoadjuvant chemotherapy and to define therapy-resistant subgroups for future therapeutic interventions.
CRIS-Team Scopus Importer:2021-03-05
Keywords: breast cancer; mutational signatures; neoadjuvant therapy; prognosis; response; whole exome sequencing

Reconstructive and Aesthetic Surgeries on the Female GenitaliaGuideline of the DGGG, DGPRAC, OEGGG and SGGG (S2k-Level, AWMF Registry No. 009/019, May 2022) - Beckmann, Matthias; Borkenhagen, Ada; Fahlbusch, Christine; Gold, Daniela; Hoffmann, Juergen; Löhrs, Bettina; Luze, Hanna; Mirastschijski, Ursula; O'Dey, Dan M.; Pöschke, Patrik; Remmel, Eugenia; Schaefer, Dirk; et al. (Geburtshilfe und Frauenheilkunde, 2023)
Aim This official guideline was coordinated and published by the German Society for Gynaecology and Obstetrics (DGGG), the German Society for Plastic, Reconstructive and Aesthetic Surgery (DGPRAC), the Austrian Society for Gynaecology and Obstetrics (OEGGG), and the Swiss Society for Gynaecology and Obstetrics (SGGG). The guideline aims to provide a consensus-based overview of reconstructive and aesthetic surgeries on female genitalia based on an evaluation of the relevant literature. Methods This S2k-guideline was developed by representative members from different medical professions on behalf of the guidelines commission of the DGGG, DGPRAC, OEGGG and SGGG using a structured consensus process. Recommendations Statements and recommendations on the epidemiology, aetiology, classification, symptoms, diagnosis, and treatment of acquired changes of the external genitalia are presented and special situations are discussed.
CRIS-Team Scopus Importer:2023-07-21
Keywords: aesthetic surgeries; female genital mutilation (FGM); female genitalia; guideline; reconstructive surgeries

Recording of the regional Origin Areas of Patients from the Molecular Tumor Board to Identify the "white Spots" in the Service Area - A joint Initiative of the Bavarian CCC WERA Alliance - Lueke, F.; Haller, F.; Utpatel, K.; Krebs, M.; Meidenbauer, Norbert; Scheiter, A.; Spörl, Silvia; Heudobler, D.; Keil, F.; Schubart, Christoph; Tögel, Lars; Einhell, S.; et al. (ONCOLOGY RESEARCH AND TREATMENT, 2022)
CRIS-Team WoS Importer:2022-11-18

Recurrent KAT6B/A::KANSL1 Fusions Characterize a Potentially Aggressive Uterine Sarcoma Morphologically Overlapping With Low-grade Endometrial Stromal Sarcoma. - Agaimy, Abbas; Clarke, Blaise A.; Kolin, David L.; Lee, Cheng-Han; Lee, Jen-Chieh; Mccluggage, W. Glenn; Pöschke, Patrik; Stöhr, Robert; Swanson, David; Turashvili, Gulisa; Beckmann, Matthias; Hartmann, Arndt; et al. (American Journal of Surgical Pathology, 2022)
With the widespread application of next-generation sequencing, the genetic landscape of uterine mesenchymal neoplasms has been evolving rapidly to include several recently identified fusion genes. Although chromosomal rearrangements involving the 10q22 and 17q21.31 loci have been reported in occasional uterine leiomyomas decades ago, the corresponding KAT6B::KANSL1 fusion has been only recently identified in 2 uterine tumors diagnosed as leiomyoma and leiomyosarcoma. We herein describe 13 uterine stromal neoplasms carrying a KAT6B::KANSL1 (n=11) and KAT6A::KANSL1 (n=2) fusion. Patient ages ranged from 33 to 81 years (median, 49 y). Tumor size was 2.6 to 23.5 cm (median, 8.2 cm). Nine tumors were myometrium-centered, and 3 had an intracavitary component. Original diagnoses were mostly low-grade endometrial stromal sarcoma (LG-ESS; 10 cases) with atypical features (limited CD10 expression, sex cord-like features, pericytic vasculature, and frequent myxoid changes). Treatment was hysterectomy±bilateral salpingo-oophorectomy (10), myomectomy (1), and curettage (2). Five patients were disease-free at 6 to 34 months, 3 (27%) died of disease at 2 to 47 months, and 3 were alive with disease at 2, 17, and 17 years. Histologically, most tumors showed variable overlap with LG-ESS, but they were generally well-circumscribed lacking the extensive permeative and angioinvasive growth typical of LG-ESS. They were composed of monotonous medium-sized oval and spindle cells arranged into diffuse sheets with prominent spiral-type arterioles and frequent pericytoma-like vascular pattern. Variable myxoid stromal changes were frequent. Mitotic activity ranged from 1 to >20 in 10 HPFs. Immunohistochemistry showed variable expression of CD10 (12/13), estrogen receptor (8/11), progesterone receptor (8/11), smooth muscle actin (9/11), desmin (4/12), h-caldesmon (2/10), calretinin (3/8), inhibin (1/7), WT1 (4/7), cyclin D1 (5/11; diffuse in only 1 case), and pankeratin (5/10). This series characterizes a KAT6B/A::KANSL1 fusion-positive uterine stromal neoplasm within the morphologic spectrum of LG-ESS but with atypical features. The relationship of these neoplasms to genuine LG-ESS remains unclear. This molecular subtype of uterine endometrial stromal sarcoma has the potential for an unfavorable clinical course despite the absence of widely invasive growth; nevertheless, analysis of more cases is necessary to delineate the phenotypic spectrum and biological potential of this tumor.
EVALuna2:504168

Reduction of Serious Adverse Events (SAE) under palbociclib treatment in patients using an interactive eHealth system - Schmidt, M.; Degenhardt, T.; Fasching, Peter; Lueftner, D.; Mueller, V.; Thomssen, C.; Schem, C.; Witzel, I.; Decker, T.; Tesch, H.; Kuemmel, S.; Uleer, C.; et al. (EUROPEAN JOURNAL OF CANCER, 2020)
CRIS-Team WoS Importer:2020-11-13

Reduction of Serious Adverse Events (SAE) under palbociclib treatment in patients using an interactive eHealth system - Schmidt, M.; Degenhardt, T.; Fasching, Peter; Lüftner, D.; Müller, V.; Thomssen, C.; Schem, C.; Witzel, I.; Decker, T.; Tesch, H.; Kümmel, S.; Uleer, C.; et al. (European Journal of Cancer, 2020)
CRIS-Team Scopus Importer:2020-10-16

Refined cut-off for TP53 immunohistochemistry improves prediction of TP53 mutation status in ovarian mucinous tumors: implications for outcome analyses - Kang, Eun Young; Cheasley, Dane; LePage, Cecile; Wakefield, Matthew J.; da Cunha Torres, Michelle; Rowley, Simone; Salazar, Carolina; Xing, Zhongyue; Allan, Prue; Bowtell, David D.L.; Mes-Masson, Anne Marie; Provencher, Diane M.; et al. (Modern Pathology, 2021)
TP53 mutations are implicated in the progression of mucinous borderline tumors (MBOT) to mucinous ovarian carcinomas (MOC). Optimized immunohistochemistry (IHC) for TP53 has been established as a proxy for the TP53 mutation status in other ovarian tumor types. We aimed to confirm the ability of TP53 IHC to predict TP53 mutation status in ovarian mucinous tumors and to evaluate the association of TP53 mutation status with survival among patients with MBOT and MOC. Tumor tissue from an initial cohort of 113 women with MBOT/MOC was stained with optimized IHC for TP53 using tissue microarrays (75.2%) or full sections (24.8%) and interpreted using established criteria as normal or abnormal (overexpression, complete absence, or cytoplasmic). Cases were considered concordant if abnormal IHC staining predicted deleterious TP53 mutations. Discordant tissue microarray cases were re-evaluated on full sections and interpretational criteria were refined. The initial cohort was expanded to a total of 165 MBOT and 424 MOC for the examination of the association of survival with TP53 mutation status, assessed either by TP53 IHC and/or sequencing. Initially, 82/113 (72.6%) cases were concordant using the established criteria. Refined criteria for overexpression to account for intratumoral heterogeneity and terminal differentiation improved concordance to 93.8% (106/113). In the expanded cohort, 19.4% (32/165) of MBOT showed evidence for TP53 mutation and this was associated with a higher risk of recurrence, disease-specific death, and all-cause mortality (overall survival: HR = 4.6, 95% CI 1.5-14.3, p = 0.0087). Within MOC, 61.1% (259/424) harbored a TP53 mutation, but this was not associated with survival (overall survival, p = 0.77). TP53 IHC is an accurate proxy for TP53 mutation status with refined interpretation criteria accounting for intratumoral heterogeneity and terminal differentiation in ovarian mucinous tumors. TP53 mutation status is an important biomarker to identify MBOT with a higher risk of mortality.
CRIS-Team Scopus Importer:2021-02-05

Refined histopathological predictors of BRCA1 and BRCA2 mutation status: a large-scale analysis of breast cancer characteristics from the BCAC, CIMBA, and ENIGMA consortia - Spurdle, Amanda B.; Couch, Fergus J.; Parsons, Michael T.; Mcguffog, Lesley; Barrowdale, Daniel; Bolla, Manjeet K.; Wang, Qin; Healey, Sue; Schmutzler, Rita Katharina; Wappenschmidt, Barbara; Rhiem, Kerstin; Hahnen, Eric; et al. (Breast Cancer Research, 2014)
The distribution of histopathological features of invasive breast tumors in BRCA1 or BRCA2 germline mutation carriers differs from that of individuals with no known mutation. Histopathological features thus have utility for mutation prediction, including statistical modeling to assess pathogenicity of BRCA1 or BRCA2 variants of uncertain clinical significance. We analyzed large pathology datasets accrued by the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA) and the Breast Cancer Association Consortium (BCAC) to reassess histopathological predictors of BRCA1 and BRCA2 mutation status, and provide robust likelihood ratio (LR) estimates for statistical modeling.Selection criteria for study/center inclusion were estrogen receptor (ER) status or grade data available for invasive breast cancer diagnosed younger than 70 years. The dataset included 4,477 BRCA1 mutation carriers, 2,565 BRCA2 mutation carriers, and 47,565 BCAC breast cancer cases. Country-stratified estimates of the likelihood of mutation status by histopathological markers were derived using a Mantel-Haenszel approach.ER-positive phenotype negatively predicted BRCA1 mutation status, irrespective of grade (LRs from 0.08 to 0.90). ER-negative grade 3 histopathology was more predictive of positive BRCA1 mutation status in women 50 years or older (LR = 4.13 (3.70 to 4.62)) versus younger than 50 years (LR = 3.16 (2.96 to 3.37)). For BRCA2, ER-positive grade 3 phenotype modestly predicted positive mutation status irrespective of age (LR = 1.7-fold), whereas ER-negative grade 3 features modestly predicted positive mutation status at 50 years or older (LR = 1.54 (1.27 to 1.88)). Triple-negative tumor status was highly predictive of BRCA1 mutation status for women younger than 50 years (LR = 3.73 (3.43 to 4.05)) and 50 years or older (LR = 4.41 (3.86 to 5.04)), and modestly predictive of positive BRCA2 mutation status in women 50 years or older (LR = 1.79 (1.42 to 2.24)).These results refine likelihood-ratio estimates for predicting BRCA1 and BRCA2 mutation status by using commonly measured histopathological features. Age at diagnosis is an important variable for most analyses, and grade is more informative than ER status for BRCA2 mutation carrier prediction. The estimates will improve BRCA1 and BRCA2 variant classification and inform patient mutation testing and clinical management.
EVALuna2:9304

Regulation of murine placentogenesis by the retroviral genes Syncytin-A, Syncytin-B and Peg10 - Henke, Christine; Ruebner, Matthias; Faschingbauer, Florian; Stolt, Claus; Schäfer, Natascha; Lang, Nadine; Beckmann, Matthias; Strissel, Pamela; Strick, Reiner (Differentiation, 2013)
The murine placenta has a trichorial structure with two multinucleated syncytiotrophoblast (SCT) layers representing a barrier between the maternal and fetal blood system. Genes of endogenous retroviruses and retrotransposon-derived paternally expressed genes (Peg), remnants of past infections and integrations in the genome, have essential functions in placentogenesis. Previous studies showed that the envelope genes Syncytin-A and Syncytin-B were essential for cell-cell fusion of the SCT. The goal of this study was to analyze the temporal localization and expression of nine genes throughout placental development from embryonic day (E)8.5 to E18.5 using in situ-hybridization and absolute RNA-quantification. These included a comparison of previously characterized genes from the labyrinth Syncytin-A, Syncytin-B, Gcm1, the junctional zone PL-1, PL-2, Plf, Tpbpa with two further characterized genes Peg10 and Tpbpb. Syncytin-A and Syncytin-B RNA localized to SCT-I and SCT-II, respectively. Peg10 RNA localized to all extraembryonic tissues, specifically to the parietal and sinusoidal TGC of the labyrinth layer, which is in contact with SCT-I and the maternal blood. All three retroviral/retrotransposon-derived genes showed the highest expression at E16.5, but Peg10 with 188,917.1 molecules/ng cDNA was 208-fold and 106.8-fold higher expressed than Syncytin-A and Syncytin-B, respectively. Tpbpb localized to the junctional zone and showed the highest expression at E16.5 along with PL-2, Plf, Tpbpa, but not PL-1, which decreased in expression at E10.5. To investigate a role of Syncytin-A, Syncytin-B and Peg10 in cell-cell fusion, we established a cell culture system with fractionated primary trophoblasts from murine placentae. Culturing trophoblasts for up to 72h partly resembled trophoblast development in vivo according to the nine marker genes. Knockdown of Syncytin-A demonstrated a functional regulation of cell-cell fusion, where knockdown of Peg10 showed no involvement in cell fusion. Due to the expression of Peg10 in TGCs, we propose an essential functional role in the fetal-maternal blood system.
EVALuna2:4934

Re-irradiation of the chest wall for local breast cancer recurrence : Results of salvage brachytherapy with hyperthermia - Auoragh, A.; Strnad, Vratislav; Ott, O. J.; Beckmann, Matthias; Fietkau, Rainer (Strahlentherapie und Onkologie, 2016)
Following mastectomy and adjuvant external beam radiation therapy in patients with breast cancer, the incidence of local or locoregional recurrence is approximately 9 % (2-20 %). Alongside the often limited possibilities of surgical treatment, radiation therapy combined with superficial hyperthermia is the most effective local therapy. In the present work, a retrospective analysis of salvage brachytherapy combined with superficial hyperthermia for chest wall recurrences is presented.Between 2004 and 2011, 18 patients with a total of 23 target volumes resulting from chest wall recurrences after previously mastectomy and external beam radiation therapy (median 56 Gy, range 50-68 Gy) were treated with superficial brachytherapy as salvage treatment: 8 patients (44 %) had macroscopic tumor, 3 (17 %) had microscopic tumor (R1), and 7 (39 %) had undergone R0 resection and were treated due to risk factors. A dose of 50 Gy was given (high-dose rate [HDR] and pulsed-dose rate [PDR] procedures). In all, 5 of 23 patients (22 %) received additional concurrent chemotherapy, and in 20 of 23 (87 %) target volumes additional superficial hyperthermia was carried out twice weekly.The 5-year local recurrence-free survival was 56 %, the disease-free survival was 28 %, and a 5-year overall survival was 22 %. Late side effects Common Toxicity Criteria (CTC) grade 3 were reported in 17 % of the patients: 2 of 18 (11 %) had CTC grade 3 fibrosis, and 1 of 18 (6 %) had a chronic wound healing disorder.Re-irradiation as salvage brachytherapy with superficial hyperthermia for chest wall recurrences is a feasible and safe treatment with good local control results and acceptable late side effects.
EVALuna2:18364

Relevance of tumour-infiltrating lymphocytes, PD-1 and PD-L1 in patients with high-risk, nodal-metastasised breast cancer of the German Adjuvant Intergroup Node–positive study - Noske, Aurelia; Möbus, Volker; Weber, Karsten; Schmatloch, Sabine; Weichert, Wilko; Köhne, Claus Henning; Solbach, Christine; Ingold Heppner, Barbara; Steiger, Katja; Müller, Volkmar; Fasching, Peter; Karn, Thomas; et al. (European Journal of Cancer, 2019)
Background: Immune cell infiltration in breast cancer is important for the patient's prognosis and response to systemic therapies including immunotherapy. We sought to investigate the prevalence of tumour-infiltrating lymphocytes (TILs)and their association with immune checkpoints such as programmed cell death 1 (PD-1)and programmed cell death ligand 1 (PD-L1)in high-risk, node-positive breast cancer of the adjuvant German Adjuvant Intergroup Node–positive (GAIN-1)trial. Patients and methods: We evaluated TILs by haematoxylin and eosin staining and PD-1 and PD-L1 (SP263 assay)expression by immunohistochemistry in 1318 formalin-fixed, paraffin-embedded breast carcinomas. The association of TILs with PD-1, PD-L1, molecular intrinsic subtypes, outcome and therapy regimens (dose-dense [dd]epirubicin, paclitaxel and cyclophosphamide [EPC]and dd epirubicin, cyclophosphamide, paclitaxel and capecitabine [EC-PwX])was statistically tested. Results: Overall TILs density was significantly associated with the expression of PD-1 and PD-L1 in immune cells (each p < 0.0001)and PD-L1 in tumour cells (p = 0.0051). TILs were more common in triple-negative breast cancer (TNBC)and human epidermal growth factor receptor 2 (HER2)HER2-positive tumours (each p < 0.0001). On multivariate Cox regression analyses, patients with breast cancer without TILs had an unfavourable disease-free survival (DFS)in the EPC arm compared with the EC-PwX arm (hazard ratio [HR]= 0.69 [0.44–1.06], p = 0.0915); but no differences were seen in tumours with TILs (HR = 1.24 [0.92–1.67], p = 0.1566, interaction p = 0.0336). PD-1–positive immune cells in TNBC were associated with a significantly better DFS (HR = 0.50 [0.25–0.99], p = 0.0457). PD-L1 expression had no impact on patient outcome. Conclusions: TILs predict the benefit of intensified ddEPC compared with ddEC-PwX therapy in node-positive, high-risk breast cancer. TILs, PD-1 and PD-L1 are linked to each other indicating tumour immunogenicity. Moreover, PD-1–positive immune cells have a positive prognostic impact in TNBC. Clinical trial: NCT00196872.
CRIS-Team Scopus Importer:2019-05-17
Keywords: Adjuvant; Breast cancer; PD-1; PD-L1; Prognosis; Therapy prediction; TILs

Reliability of an e-PRO Tool of EORTC QLQ-C30 for Measurement of Health-Related Quality of Life in Patients With Breast Cancer: Prospective Randomized Trial - Wallwiener, Markus; Matthies, Lina; Simoes, Elisabeth; Keilmann, Lucia; Hartkopf, Andreas D.; Sokolov, Alexander N.; Walter, Christina B.; Sickenberger, Nina; Wallwiener, Stephanie; Feisst, Manuel; Gaß, Paul; Fasching, Peter; et al. (Journal of Medical Internet Research, 2017)
BACKGROUND: Breast cancer represents the most common malignant disease in women worldwide. As currently systematic palliative treatment only has a limited effect on survival rates, the concept of health-related quality of life (HRQoL) is gaining more and more importance in the therapy setting of metastatic breast cancer. One of the major patient-reported outcomes (PROs) for measuring HRQoL in patients with breast cancer is provided by the European Organization for Research and Treatment of Cancer (EORTC). Currently, paper-based surveys still predominate, as only a few reliable and validated electronic-based questionnaires are available. Facing the possibilities associated with evolving digitalization in medicine, validation of electronic versions of well-established PRO is essential in order to contribute to comprehensive and holistic oncological care and to ensure high quality in cancer research. OBJECTIVE: The aim of this study was to analyze the reliability of a tablet-based measuring application for EORTC QLQ-C30 in German language in patients with adjuvant and (curative) metastatic breast cancer. METHODS: Paper- and tablet-based questionnaires were completed by a total of 106 female patients with adjuvant and metastatic breast cancer recruited as part of the e-PROCOM study. All patients were required to complete the electronic- (e-PRO) and paper-based versions of the HRQoL EORTC QLQ-C30 questionnaire. A frequency analysis was performed to determine descriptive sociodemographic characteristics. Both dimensions of reliability (parallel forms reliability [Wilcoxon test] and test of internal consistency [Spearman rho and agreement rates for single items, Pearson correlation and Kendall tau for each scale]) were analyzed. RESULTS: High correlations were shown for both dimensions of reliability (parallel forms reliability and internal consistency) in the patient's response behavior between paper- and electronic-based questionnaires. Regarding the test of parallel forms reliability, no significant differences were found in 27 of 30 single items and in 14 of 15 scales, whereas a statistically significant correlation in the test of consistency was found in all 30 single items and all 15 scales. CONCLUSIONS: The evaluated e-PRO version of the EORTC QLQ-C30 is reliable for patients with both adjuvant and metastatic breast cancer, showing a high correlation in almost all questions (and in many scales). Thus, we conclude that the validated paper-based PRO assessment and the e-PRO tool are equally valid. However, the reliability should also be analyzed in other prospective trials to ensure that usability is reliable in all patient groups. TRIAL REGISTRATION: ClinicalTrials.gov NCT03132506; https://clinicaltrials.gov/ct2/show/NCT03132506 (Archived by WebCite at http://www.webcitation.org/6tRcgQuou).
EVALuna2:36167

Reliability of prenatal detection of X-linked hypohidrotic ectodermal dysplasia by tooth germ sonography - Hammersen, Johanna; Wohlfart, Sigrun; Goecke, Tamme W.; Köninger, Angela; Stepan, Holger; Gallinat, Ralph; Morris, Susan; Bücher, Katharina; Clarke, Angus; Wünsche, Stephanie; Beckmann, Matthias; Schneider, Holm; et al. (Prenatal Diagnosis, 2019)
Objective: In X-linked hypohidrotic ectodermal dysplasia (XLHED), dysfunction of ectodysplasin A1 (EDA1) due to EDA mutations results in malformation of hair, teeth, and sweat glands. Hypohidrosis, which can cause life-threatening hyperthermia, is amenable to intrauterine therapy with recombinant EDA1. This study aimed at evaluating tooth germ sonography as a noninvasive means to identify affected fetuses in pregnant carrier women. Methods: Sonography, performed at 10 study sites between gestational weeks 18 and 28, led to the diagnosis of XLHED if fewer than six tooth germs were detected in mandible or maxilla. The assessment was verified postnatally by EDA sequencing and/or clinical findings. Estimated fetal weights and postnatal weight gain of boys with XLHED were assessed using appropriate growth charts. Results: In 19 of 38 sonographic examinations (23 male and 13 female fetuses), XLHED was detected prenatally. The prenatal diagnosis proved to be correct in 37 cases; one affected male fetus was missed. Specificity and positive predictive value were both 100%. Tooth counts obtained by clinical examination corresponded well with findings on panoramic radiographs. We observed no weight deficits of subjects with XLHED in utero but occasionally during infancy. Conclusion: Tooth germ sonography is highly specific and reliable in detecting XLHED prenatally.
CRIS-Team Scopus Importer:2019-08-27

Repetitive Maturation of Oocytes From Non-Stimulated Xenografted Ovarian Tissue From a Prepubertal Patient Indicating the Independence of Human Ovarian Tissue - Raffel, Nathalie; Lotz, Laura; Hoffmann, Inge; Liebenthron, Jana; Söder, Stephan; Beckmann, Matthias; Dittrich, Ralf (Geburtshilfe und Frauenheilkunde, 2017)
Introduction: Modern anti-cancer strategies have distinctly increased survival rates; nevertheless, often accompanied by sterility. Currently, the only option for preserving fertility in prepubertal females is to cryopreserve ovarian tissue and re-transplant frozen-thawed tissue to restore fertility after treatment. Our aim was to report the occurrence of repetitive antral follicle formation and oocyte maturation in a prepubescent ovarian tissue xenograft without exogenous hormone stimulation. Material and Methods: Frozen-thawed ovarian tissue from a 6-year-old patient suffering from nephroblastoma was xenotransplanted in oophorectomized severe combined immunodeficiency (SCID) mice to evaluate follicle development. Ergebnisse: Repetitive follicle development to the antral stage occurred in the same xenograft of prepubertal ovarian tissue without exogenous hormone administration; 37 days after retrieving a maturing oocyte (this first retrieval has been previously published), another, completely mature oocyte was harvested from the xenograft. Subsequent histological evaluation of the grafted tissue showed primordial follicles, nearly all stages of developing follicles, as well as large atretic ones. Many clusters with dormant primordial follicles were also present. Conclusion: Xenotransplanted prepubertal ovarian tissue has the potential for repetitive oocyte retrieval cycles without administering exogenous hormones. The results indicate that the human ovarian tissue might be able to synchronize the hypothalamus-hypophysis-axes of the mouse to the physiological human cycle; this should be investigated in future studies.
EVALuna2:34929

Replication of Epigenetic Postpartum Depression Biomarkers and Variation with Hormone Levels - Osborne, Lauren; Clive, Makena; Kimmel, Mary; Gispen, Fiona; Guintivano, Jerry; Brown, Tori; Cox, Olivia; Judy, Jennifer; Meilman, Samantha; Braier, Aviva; Beckmann, Matthias; Kornhuber, Johannes; et al. (Neuropsychopharmacology, 2016)
DNA methylation variation at HP1BP3 and TTC9B is modified by estrogen exposure in the rodent hippocampus and was previously shown to be prospectively predictive of postpartum depression (PPD) when modeled in antenatal blood. The objective of this study was to replicate the predictive efficacy of the previously established model in women with and without a previous psychiatric diagnosis and to understand the effects of changing hormone levels on PPD biomarker loci. Using a statistical model trained on DNA methylation data from N=51 high-risk women, we prospectively predicted PPD status in an independent N=51 women using first trimester antenatal gene expression levels of HP1BP3 and TTC9B, with an area under the receiver operator characteristic curve (AUC) of 0.81 (95% CI: 0.69-0.92, p<5 × 10(-4)). Modeling DNA methylation of these genes in N=240 women without a previous psychiatric diagnosis resulted in a cross-sectional prediction of PPD status with an AUC of 0.81 (95% CI: 0.68-0.93, p=0.01). TTC9B and HP1BP3 DNA methylation at early antenatal time points showed moderate evidence for association to the change in estradiol and allopregnanolone over the course of pregnancy, suggesting that epigenetic variation at these loci may be important for mediating hormonal sensitivity. In addition both loci showed PPD-specific trajectories with age, possibly mediated by age-associated hormonal changes. The data add to the growing body of evidence suggesting that PPD is mediated by differential gene expression and epigenetic sensitivity to pregnancy hormones and that modeling proxies of this sensitivity enable accurate prediction of PPD.
EVALuna2:23791

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 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 for Pelvic Metastasis and Role of Pelvic Lymphadenectomy in Node-Positive Vulvar Cancer-Results from the AGO-VOP.2 QS Vulva Study - Woelber, Linn; Hampl, Monika; Eulenburg, Christine Zu; Prieske, Katharina; Hambrecht, Johanna; Fuerst, Sophie; Klapdor, Ruediger; Heublein, Sabine; Gaß, Paul; Rohner, Annika; Canzler, Ulrich; Becker, Sven; et al. (Cancers, 2022)
The need for pelvic treatment in patients with node-positive vulvar cancer (VSCC) and the value of pelvic lymphadenectomy (LAE) as a staging procedure to plan adjuvant radiotherapy (RT) is controversial. In this retrospective, multicenter analysis, 306 patients with primary node-positive VSCC treated at 33 gynecologic oncology centers in Germany between 2017 and 2019 were analyzed. All patients received surgical staging of the groins; nodal status was as follows: 23.9% (73/306) pN1a, 23.5% (72/306) pN1b, 20.4% (62/306) pN2a/b, and 31.9% (97/306) pN2c/pN3. A total of 35.6% (109/306) received pelvic LAE; pelvic nodal involvement was observed in 18.5%. None of the patients with nodal status pN1a or pN1b and pelvic LAE showed pelvic nodal involvement. Taking only patients with nodal status ≥pN2a into account, the rate of pelvic involvement was 25%. In total, adjuvant RT was applied in 64.4% (197/306). Only half of the pelvic node-positive (N+) patients received adjuvant RT to the pelvis (50%, 10/20 patients); 41.9% (122/291 patients) experienced recurrent disease or died. In patients with histologically-confirmed pelvic metastases after LAE, distant recurrences were most frequently observed (7/20 recurrences). Conclusions: A relevant risk regarding pelvic nodal involvement was observed from nodal status pN2a and higher. Our data support the omission of pelvic treatment in patients with nodal status pN1a and pN1b.
CRIS-Team Scopus Importer:2022-02-04
Keywords: Groin; Pelvic lymphadenectomy; Prognosis; Radiotherapy; Recurrence; Vulvar cancer

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.
EVALuna2:9204

Risk of pelvic metastasis and significance of pelvic lymphadenectomy in patients with node-positive vulvar cancer - results of the AGO-VOP.2/QS vulva study - Jaeger, A.; Hampl, M.; Zu Eulenburg, C.; Prieske, K.; Hambrecht, J.; Fuerst, S.; Klapdor, R.; Heublein, S.; Gaß, Paul; Rohner, A.; Canzler, U.; Becker, S.; et al. (GEBURTSHILFE UND FRAUENHEILKUNDE, 2022)
CRIS-Team WoS Importer:2022-11-04

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.
EVALuna2:34612

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.
EVALuna2:15283

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.
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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 Fiber Thickness and Surface Treatment of Electrospun Polycaprolactone Matrices on the Growth of Different Breast Cancer‐Associated Cells - Sivakumar, Sankaranarayanan; Schmid, Rafael; Wieland, Annalena; Strissel, Pamela; Strick, Reiner; Fischer, Lena; Thievessen, Ingo; Kataev, Elmar; Arkudas, Andreas; Horch, Raymund E.; Schubert, Dirk W.; Kengelbach-Weigand, Annika (Advanced Materials Interfaces, 2022)
Cancer models mimicking the tumor microenvironment are necessary to successfully develop and predict responses of oncological drugs. In this study, electrospun polycaprolactone (PCL) matrices are tested for the development of an in vitro breast cancer model. The effects of fiber thickness and plasma-treatment of the matrices on in vitro growth of breast cancer-associated cells, namely breast cancer cells MDA-MB-231, primary adipose-derived stem cells (ADSCs) and primary endothelial progenitor cells (EPCs) are evaluated. Surface treatment of the matrices by air-plasma leads to increased oxygen/carbon ratio and hydrophilicity. WST-8 analysis reveals that the proliferation of all three cell types increased exponentially over 12 d on all matrices. MDA-MB-231 and ADSC show a higher proliferation on nanofibers due to enhanced cellular adhesion compared to microfibers. In contrast, EPCs show a significantly higher proliferation on microfibers than on nanofibers at day 12 which can further be significantly improved by air-plasma treatment. Cross-sectioning analysis shows that cells grow on the surface of nanofibers, while microfibers have considerable cellular infiltration. These findings suggest that the electrospun PCL matrices are a suitable tool for the development of breast cancer models containing several cell types, which can ultimately lead to designing novel tumor therapies.<br

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.
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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

S2k-Leitlinie Diagnostik und Therapie der Endometriose – Anforderungen an die Pathologie - Horn, Lars-Christian; Hohn, Anne Kathrin; Burghaus, Stefanie; Schafer, Sebastian Daniel; Ulrich, Uwe Andreas; Schmidt, Dietmar (Pathologe, 2021)
The present article summarises the recommendations for the handling, histopathological workup, diagnostics and reporting in surgical pathology of biopsies and resection specimens in patients with the clinical diagnosis of endometriosis. In addition to practical aspects of pathology, the guidelines also take into account the clinical requirements for histopathology for the optimal diagnosis and therapy of the patients. Based on the definition of endometriosis of the corpus uteri (adenomyosis uteri) most commonly used in the pathological literature, this was defined in the guidelines as the detection of the endometriosis focus in the myometrium at a distance from the endomyometrial border of a medium-sized visual field (100x magnification), which in metric units corresponds to around 2.5 mm. In bowel resection specimens, the status of the resection margins had to be documented within the histopathological report. Also mentioned are the requirements for the reporting of carcinomas associated with endometriosis, including the immunohistochemical evaluation of steroid hormone receptors and mismatch repair proteins.
CRIS-Team WoS Importer:2021-10-15

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.
EVALuna2:17602

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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S3-Leitlinie „Vaginale Geburt am Termin“ aus anästhesiologischer Sicht - Helmer, P.; Skazel, T.; Wenk, M.; Von Kaisenberg, C.; Abou-Dakn, M.; Papsdorf, M.; Abu Hmeidan, F.; Kehl, Sven; Meybohm, P.; Kranke, Peter (Anaesthesist, 2021)
The publication of the new S3 guidelines on “full-term vaginal birth” and the guidelines on cesarean section, also published in 2020, provide further steps towards the promotion of evidence-based medicine in obstetrics, even if the exact configuration of neonatal monitoring during birth, in particular, is still the subject of current discussions. The multiprofessionality in the medical supervision of a birth is also fundamentally well-represented in the compilation of the S3 guidelines by the participating actors and specialist societies. Important from an anesthesiological perspective is the fact that neuraxial procedures still represent the gold standard in obstetric analgesia. With remifentanil PCA an alternative option is available that enables a reliable analgesia to be accomplished, e.g. when there are contraindications to performing neuraxial methods, if this is appropriate under the prevailing circumstances (1:1 support and appropriate monitoring). During an uncomplicated birth the strict fasting rules are relaxed. Overall, the guidelines underline the importance of self-determination and self-control for the expectant mother and give the highest priority to the safety and well-being of mother and child; however, this presupposes that the expectant mother is sufficiently informed about the value of neuraxial analgesia. For this it appears to be of importance to initiate information proposals, which go beyond the usual information sessions for parents that are often organized exclusively by midwives.
CRIS-Team Scopus Importer:2021-09-17
Keywords: CTG; Epidural analgesia; Evidence based medicine; Obstetric anesthesia; Remifentanil PCA

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 Fc-EDA, a recombinant ectodysplasin A1 replacement protein, in human subjects - Körber, Iris; Klein, Ophir D.; Morhart, Patrick; Faschingbauer, Florian; Grange, Dorothy K.; Clarke, Angus; Bodemer, Christine; Maitz, Silvia; Huttner, Kenneth; Kirby, Neil; Durand, Caroline; Schneider, Holm (British Journal of Clinical Pharmacology, 2020)
In X-linked hypohidrotic ectodermal dysplasia, the most frequent ectodermal dysplasia, an inherited deficiency of the signalling protein ectodysplasin A1 (EDA1) impairs the development of the skin and its appendages, various eccrine glands, and dentition. The severe hypohidrosis common to X-linked hypohidrotic ectodermal dysplasia patients may lead to life-threatening hyperthermia, especially during hot weather or febrile illness. Fc-EDA, an EDA1 replacement protein known to prevent the disease in newborn animals, was tested in 2 clinical trials (human adults and neonates) and additionally administered under compassionate use to 3 infants in utero. The data support the safety of Fc-EDA and efficacy if applied prenatally. Anti-drug antibodies were detected after intravenous administration in adult males and nonpregnant females, but not in pregnant women when Fc-EDA was delivered intra-amniotically. Most importantly, there was no detectable immune response to the investigational drug in neonates treated by intravenous infusions and in infants who had received Fc-EDA in utero. In conclusion, the safety profile of this drug encourages further development of prenatal EDA1 replacement therapy.
CRIS-Team Scopus Importer:2020-05-02
Keywords: drug safety; ectodermal dysplasia; ectodysplasin A; immunogenicity; prenatal therapy; protein replacement

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.
EVALuna2:34632

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.
EVALuna2:17600

SARS-CoV-2 Infection in Pregnancy and Incidence of Congenital Malformations - Is there a Correlation? Analysis of 8032 Pregnancies from the CRONOS Registry SARS-CoV-2-Infektion in der Schwangerschaft und Auftreten von angeborenen Fehlbildungen - Besteht ein Zusammenhang? Auswertung von 8032 Schwangerschaften aus dem CRONOS-Register - Hofbauer, Anna; Schneider, Holm; Kehl, Sven; Reutter, Heiko Martin; Pecks, Ulrich; Andresen, Kristin; Morhart, Patrick (Zeitschrift für Geburtshilfe und Neonatologie, 2024)
Background Based on single case reports, the COVID-19 Related Obstetric and Neonatal Outcome Study (CRONOS) registry, sponsored by the German Society for Perinatal Medicine (DGPM), investigated the likelihood that SARS-CoV-2 infections of the mother in (early) pregnancy cause embryopathies and/or fetopathies. Material/Methods The CRONOS registry enrolled a total of 8032 women with confirmed SARS-CoV-2 infection during pregnancy at more than 130 participating hospitals from April 2020 to February 2023. Both maternal and fetal data were documented and the anonymized multicenter data were analyzed. Results Of 7142 fully documented pregnancies (including postnatal data), 140 showed congenital malformations. 8.57% of the mothers had had a SARS-CoV-2-infection in the 1st trimester and 36.43% in the 2nd trimester. In 66 cases with congenital malformations (47.14%), the malformation was only detected after the diagnosis of a maternal SARS-CoV-2 infection. The overall prevalence of congenital malformations in this cohort was 1.96%, compared to a prevalence of 2.39% reported in the EUROCAT (European network of population-based registries for the epidemiological surveillance of congenital anomalies) pre-pandemic registry between 2017-2019. Discussion Our multicenter data argue against a link between maternal SARS-CoV-2 infection in early pregnancy and congenital malformation.
CRIS-Team Scopus Importer:2024-02-23
Keywords: Coronavirus; COVID-19; CRONOS-registry; embryopathy; fetopathy; malformations

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

Schmerztherapie – ein Stiefkind der Frauenheilkunde? Endometriose – ein Stiefkind der Schmerzmedizin? - Burghaus, Stefanie; Häuser, Winfried (Schmerz, 2021)
CRIS-Team Scopus Importer:2021-06-11

Schwangerschaftscholestase: In Zusammenarbeit mit der AG Geburtshilfe und Pränatalmedizin in der Deutschen Gesellschaft für Gynäkologie und Geburtshilfe – Sektion Maternale Erkrankungen - Hagenbeck, Carsten; Pecks, Ulrich; Lammert, Frank; Hütten, Matthi﻿as ﻿C; Borgmeier, Felix; Fehm, Tanja; Schleußner, Ekkehard; Maul, Holger; Kehl, Sven; Hamza, Amr; Keitel, Verena (Gynäkologe, 2021)
Intrahepatic cholestasis of pregnancy (ICP) is the most frequent pregnancy-specific liver disease. It is characterized by pruritus and an accompanying elevation of serum bile acid concentrations and/or alanine aminotransferase (ALT), which are the key parameters in the diagnosis. Despite good maternal prognosis, elevated bile acid concentration in maternal blood is an influencing factor to advers fetal outcome. The ICP is associated with increased rates of preterm birth, neonatal unit admission and stillbirth. This is the result of acute fetal asphyxia as opposed to a chronic uteroplacental insufficiency. Reliable monitoring or predictive tools (e.g. cardiotocography (CTG) or ultrasound) that help to prevent advers events are yet to be explored. Medicinal treatment with ursodeoxycholic acid (UDCA) does not demonstrably reduce adverse perinatal outcomes but does improve pruritus and liver function test results. Bile acid concentrations and gestational age should be used as indications to determine delivery. There is a high risk of recurrence in subsequent pregnancies.
CRIS-Team Scopus Importer:2021-05-14
Keywords: Bile acids and salts; Liver diseases; Pruritus; Stillbirth; Ursodeoxycholic acid

Searching the web: a survey on the quality of advice on postnatal sequelae of intrauterine growth restriction and the implication of developmental origins of health and disease - Perzel, S.; Hübner, Hanna; Rascher, Wolfgang; Menendez-Castro, C.; Fahlbusch, F. B.; Hartner, Andrea (Journal of Developmental Origins of Health and Disease, 2017)
Intrauterine growth restriction (IUGR) and fetal growth restriction (FGR) are pregnancy complications associated with morbidity in later life. Despite a growing body of evidence from current research on developmental origins of health and disease (DOHaD), little information is currently provided to parents on long-term metabolic, cardiovascular and neurologic consequences. As parents strongly rely on internet-based health-related information, we examined the quality of information on IUGR/FGR sequelae and DOHaD in webpages used by laypersons. Simulating non-clinicians experience, we entered the terms 'IUGR consequences' and 'FGR consequences' into Google and Yahoo search engines. The quality of the top search-hits was analyzed with regard to the certification through the Health On the Net Foundation (HON), currentness of cited references, while reliability of information and DOHaD-related consequences were assessed via the DISCERN Plus score (DPS). Overall the citation status was not up-to-date and only a few websites were HON-certified. The results of our analysis showed a dichotomy between the growing body of evidence regarding IUGR/FGR-related sequelae and lack of current guidelines, leaving parents without clear directions. Furthermore, detailed information on the concept of DOHaD is not provided. These findings emphasize the responsibility of the individual physician for providing advice on IUGR/FGR-related sequelae, monitoring and follow-up.
EVALuna2:34005

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.
EVALuna2:6578

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.
EVALuna2:209953

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.
EVALuna2:14618

Senology in Gynaecology Specialist Training: a Baseline Survey from 2014 - Puppe, J.; Dieterich, Max; Bayer, C.; Neiman, J.; Mendes, M. De Sousa; Gaß, Paul; Lermann, J.; Schott, Sarah (Geburtshilfe und Frauenheilkunde, 2016)
Introduction: Qualified training in senology is essential for maintaining adequate, high quality patient care. In order to meet the needs of doctors in training and those of the medical infrastructure it is necessary to assess the quality of training regularly, to enable its adaption and optimisation.Methods:We developed a comprehensive, 10 item online questionnaire to assess the quality of specialised training in senology. This questionnaire was sent to 4000 speciality trainees and young specialists countrywide via the DGGG newsletter and was accessible for over four weeks.Results:111 obstetrics and gynaecology speciality trainees participated in this national survey, 79 % of whom were female. 33 % of participants were working at university hospitals, 29 % at hospitals offering maximal level care without an associated medical faculty, 37 % at hospitals offering primary and secondary level care and 2 % at gynaecology practices. 25 % of participants could imagine working in the field of senology in future. On average the current perception of general specialist training was satisfactory. Specialist trainees at university hospitals rated training in senology highest (score: 2.95) compared to those at other hospitals. A fixed rotation through a breast centre offering comprehensive advanced training was seen as a potential improvement to senology training.Conclusions:This is the first survey of specialised training in senology to be conducted in Germany. Results showed that there is significant potential for young doctors to enter the speciality in future. There are also significant differences in the perceived quality of senology training between training facilities. This survey aimed to determine the quality of specialised training at senology centres and hopes to contribute to a sustainable improvement in training. The intention is to continue to make senology attractive to gynaecologists and to ensure well-grounded training.
EVALuna2:33448

Sentinel lymph node detection by means of indocyanine green using the Karl Storz VITOM® fluorescence camera: a comparison between primary sentinel lymph node biopsy versus sentinel lymph node biopsy after neoadjuvant chemotherapy - Staubach, Petronilla; Scharl, Anton; Ignatov, Atanas; Ortmann, Olaf; Inwald, Elisabeth C.; Hildebrandt, Thomas; Gerken, Michael; Klinkhammer-Schalke, Monika; Scharl, Sophia; Papathemelis, Thomas (Journal of Cancer Research and Clinical Oncology, 2020)
Purpose: The usage of radioactive Technetium99m (Tc99m) colloid for the purpose of sentinel lymph node biopsy (SLNB) in early breast cancer is considered the gold standard in Germany. However, new tracers, such as near-infrared (NIR) imaging agents like indocyanine green (ICG) could offer an alternative in future, as they overcome drawbacks associated with radioactive Technetium99m (Tc99m) like limited availability, high costs and radioactivity exposure for both patients and surgeons. Methods: In this double-arm retrospective study, we sought to establish the usefulness of indocyanine green as an alternative or an addition to the conventional Technetium99m (Tc99m) in the identification of the SLN in early breast cancer. Results: Among the 161 patients who underwent primary SLNB, 34 patients had at least 1 SLN with metastasis. Among these patients with SLN metastasis, 33 had the SLN detected by ICG; while 31 had the SLN detected by Tc99m. The conventional Technetium99m radiotracer failed to detect 2 patients with metastasis in this Arm of the study. Among the 87 patients who underwent SLNB after NACT, 13 patients had at least 1 SLN with metastasis. Among these 13 patients with SLN metastasis, ICG and Tc99m had detected the SLN among 12 patients, while 1 patient had been detected by ICG alone. Conclusions: Our results show that ICG is as effective as the radioisotope for SLNB even among patients who have undergone NACT. This trial is registered with the German Clinical Trial Register, ID: DRKS00013606.
CRIS-Team Scopus Importer:2020-12-04
Keywords: Breast cancer; Indocyanine green; Neoadjuvant therapy; Sentinel biopsy

Sequential use of double-balloon catheter and oral misoprostol versus oral misoprostol alone for induction of labour at term (CRBplus trial): a multicentre, open-label randomised controlled trial - Kehl, Sven; Ziegler, J.; Schleussner, E.; Tuschy, B.; Berlit, S.; Kirscht, J.; Haegele, F.; Weiss, C.; Siemer, J.; Suetterlin, M. (Bjog-An International Journal of Obstetrics and Gynaecology, 2015)
To evaluate the efficacy of inducing labour using a double-balloon catheter and oral misoprostol sequentially, in comparison with oral misoprostol alone.A multicentre randomised controlled trial.Five hospitals in Germany.A total of 326 pregnant women with an unfavourable cervix undergoing labour induction at term.Women were randomly assigned according to a computer-generated allocation sequence to sequential use of double-balloon catheter and oral misoprostol (study group) or oral misoprostol alone (control group). In the study group, the double-balloon catheter was used the first day before starting oral misoprostol the second day.The primary outcome measure was the induction-to-delivery interval, and a further outcome parameter was delivery within 48 hours.The median times for induction of labour until delivery were 32.4 hours in the study group and 22.5 hours in the control group (P = 0.004). This difference was not seen when evaluating according to parity (nulliparous, P = 0.19; parous, P = 0.06). The rate of vaginal delivery within 48 hours did not differ between both groups. The number of applications of misoprostol (two versus three, P < 0.001) and the dose of misoprostol used was lower in the study group (100 versus 200 ?g, P < 0.001). In the study group, there were more Apgar scores of <7 at 5 minutes (8 versus 1, P = 0.04).The use of a double-balloon catheter on the first day, before starting oral misoprostol on the second day, did not improve the induction to delivery interval and the rate of delivery within 48 hours, in comparison with oral misoprostol alone.
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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)
EVALuna2:33318

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.
EVALuna2:17569

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.
EVALuna2:33190

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)
EVALuna2:32993

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.
EVALuna2:34710

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 (Zeitschrift für Geburtshilfe und Neonatologie, 2018)
Objective of this randomized-controlled multicenter-trial was 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 perinatal outcome. Pregnant women at term were randomized in AFI or SDP group for assessing amniotic fluid at four unversitary hospitals. These two groups were not different with regards to primary outcome parameter (rate of postpartum admission to NICU), but concerning secondary outcome parameters: there were significantly more cases with the diagnosis oligohydramnios (9,8 vs. 2.2%), more induction of labour for oligohydrmanios (12.7 vs. 3.6%) and more abnormal CTG (32.3 vs. 26.2%) in the AFI group. None of the methods were superior to predict adverse perinatal outcome. However, the probability to diagnose oligohydramnios and to induce labour for oligohydramnios was higher when AFI technique was used.
EVALuna2:210072

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

Skin irritability to sodium lauryl sulfate is associated with increased positive patch test reactions - Schwitulla, Judith; Brasch, J.; Löffler, H.; Schnuch, A.; Geier, J.; Uter, Wolfgang (British Journal of Dermatology, 2014)
As previous observations have indicated an inter-relationship between irritant and allergic skin reactions we analysed data of synchronous allergen and sodium lauryl sulfate (SLS) patch tests in terms of a relationship between SLS responsiveness and allergic patch test reactions.To analyse differences in terms of allergen-specific and overall reaction profiles between patients with vs. those without an irritant reaction to SLS.Clinical data of 26 879 patients patch tested from 2008 to 2011 by members of the Information Network of Departments of Dermatology were analysed. After descriptive analyses, including the MOAHLFA index, the positivity ratio and the reaction index, a negative binomial hurdle model was adopted to investigate the correlation between SLS reactivity and positive patch test reactions.Men, patients aged >= 40 years and patients with an occupational dermatitis background were over-represented in the SLS-reactive group. Patients with an irritant reaction to SLS showed a higher proportion of weak positive reactions, as well as more questionable and irritant reactions to contact allergens than patients not reactive to SLS. The risk of an additional positive patch test reaction increased by 22% for SLS-reactive patients compared with those who were SLS negative.The marked association between SLS reactivity and the number of positive reactions in patch test patients may be due to nonspecific increased skin reactivity at the moment of patch testing only. However, increased SLS reactivity could also be due to longer-lasting enhanced skin irritability, which may have promoted (poly-)sensitization. Further studies, for example with longitudinal data on patients repeatedly patch tested with SLS and contact allergens, are necessary.
EVALuna2:5456

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

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.
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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.
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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.
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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.
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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

Species differences of 11beta-hydroxysteroid dehydrogenase type 2 function in human and rat term placenta determined via LC-MS/MS - Heussner, Kirsten; Rübner, Matthias; Hübner, Hanna; Rascher, Wolfgang; Menendez-Castro, Carlos; Hartner, Andrea; Fahlbusch, Fabian B.; Rauh, Manfred (Placenta, 2016)
INTRODUCTION: Glucocorticoid-induced fetal programming has been associated with negative metabolic and cardiovascular sequelae in the adult. The placental enzyme 11beta-hydroxysteroid dehydrogenase type 2 (11β-HSD2) shields the fetus from maternal glucocorticoid excess by catalyzing the conversion of these hormones into biologically inactive derivatives. In vivo experiments addressing placental barrier function are mostly conducted in rodents. Therefore we set out to characterize species-specific differences of rat and human placental 11β-HSD2 steroid turnover, introducing Liquid Chromatography Tandem Mass-Spectrometry (LC-MS/MS) as a tool for rat tissue analysis. MATERIALS AND METHODS: Using LC-MS/MS we determined corticotropin-releasing hormone (CRH), cortisol (F), cortisone (E), corticosterone (B) and 11-dehydrocorticosterone (A) in human and rat placenta at term and measured the enzymatic 11β-HSD glucocorticoid conversion-rates in placental microsomes of both species. In parallel, further glucocorticoid derivatives and sex steroids were determined in the same placental samples. RESULTS: In contrast to the human placenta, we did not detect CRH in the rat placenta. While cortisol (F) and cortisone (E) were exclusively present in human term placenta (E/F-ratio >1), rat placenta showed significant levels of corticosterone (B) and 11-dehydrocorticosterone (A), with an A/B-ratio <1. In line with these species-specific findings, human placenta showed a prominent 11β-HSD2 activity, while in rat placenta higher 11β-HSD1 glucocorticoid turnover rates were determined. DISCUSSION: Placental steroid metabolism of human and rat shows relevant species-specific differences, especially regarding the barrier function of 11β-HSD2 at term. The exclusive expression of CRH in the human placenta further points to relevant differences in the regulation of parturition in rats. Consideration of these findings is warranted when transferring results from rodent placental glucocorticoid metabolism into humans.
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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.
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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.
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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.
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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.
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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)
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Statement of the AGG supported by DGGG and DGPGM on the S3 Guideline "Vaginal Birth at Term" - Berger, Richard; Maul, Holger; Kehl, Sven; Schiermeier, Sven; Schlembach, Dietmar; Kainer, Franz; Abou-Dakn, Michael (Geburtshilfe und Frauenheilkunde, 2021)
CRIS-Team WoS Importer:2021-09-03

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 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.
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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

Stereotactic vacuum-assisted breast biopsy (VABB)–a patients' survey - Eller, Achim; Janka, Rolf Matthias; Lux, Michael P.; Saake, Marc; Schulz-Wendtland, Rüdiger; Uder, Michael; Wenkel, Evelyn (Anticancer Research, 2014)
To analyze how patients experience Stereotactic guided vacuum-assisted breast biopsy (VABB) both physically and mentally.Two hundred and eleven consecutive women underwent VABB using one of two different biopsy devices (ATEC® and Mammotome®). Patients were queried using a questionnaire.One hundred and eighty-nine patients were included. 90% would again prefer VABB over a surgical biopsy. Average grading for the condition during the procedure was 2.5 (very good to good) and 2.1 (very good) for the condition the week following VABB. Minor complications were mentioned in 37%. (>90% pain and hematoma). 97% of the women were satisfied by the cosmetic results. Patients with malignant histology and younger age experienced the procedure significantly worse. A significant higher rate of minor complications was found in younger patients and in the ATEC® group.VABB is a physical and mental stressor to the women. Nonetheless, the majority of women indeed prefer the VABB.
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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

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.
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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.
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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.
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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.
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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.
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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.
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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.
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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

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

Tetramerization of human guanylate-binding protein 1 is mediated by coiled-coil formation of the C-terminal α-helices - Syguda, Adrian; Bauer, Michael; Benscheid, Utz; Ostler, Nicole; Naschberger, Elisabeth; Ince, Semra; Stürzl, Michael; Herrmann, Christian (Febs Journal, 2012)
The human guanylate-binding protein 1 (hGBP1) is a large GTP-binding protein belonging to the dynamin family, a common feature of which is nucleotide-dependent assembly to homotypic oligomers. Assembly leads to stimulation of GTPase activity, which, in the case of dynamin, is responsible for scission of vesicles from membranes. By yeast two-hybrid and biochemical experiments we addressed intermolecular interactions between all subdomains of hGBP1 and identified the C-terminal subdomain, α12/13, as a new interaction site for self-assembly. α12/13 represents a stable subdomain of hGBP1, as shown by CD spectroscopy. In addition to contacts between GTPase domains leading to dimer formation, the interaction between two α12/13 subdomains, in the course of GTP hydrolysis, results in tetramer formation of the protein. With the help of CD spectroscopy we showed coiled-coil formation of two α12/13 subdomains and concentration-dependent measurements allow estimating a value for the dissociation constant of 7.3 μm. We suggest GTP hydrolysis-driven release of the α12/13 subdomain, making it available for coiled-coil formation. Furthermore, we can demonstrate the biological relevance of hGBP1 tetramer formation in living cells by chemical cross-link experiments. © 2012 FEBS.
Created from Fastlane, Scopus look-up
Keywords: aluminum fluoride; dynamin; protein dimer; protein-protein association; self-assembly

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.
EVALuna2:202794

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).
EVALuna2:51629

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.
EVALuna2:17461

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 COVID-19 pandemic and its impact on medical teaching in obstetrics and gynecology - A nationwide expert survey among teaching coordinators at German university hospitals - Riedel, M.; Amann, Niklas; Recker, F.; Weiss, M.; Riedel, F. (GEBURTSHILFE UND FRAUENHEILKUNDE, 2022)
CRIS-Team WoS Importer:2022-11-04

The COVID-19 pandemic and its impact on medical teaching in obstetrics and gynecology-A nationwide expert survey among teaching coordinators at German university hospitals - Riedel, Maximilian; Amann, Niklas; Recker, Florian; Hennigs, André; Heublein, Sabine; Meyer, Bastian; Karge, Anne; Eisenkolb, Gabriel; Lammert, Jacqueline; Graf, Anna; Klein, Evelyn; Weiss, Martin; et al. (PLoS ONE, 2022)
PURPOSE: The COVID-19 pandemic has imposed severe challenges on medical education at German university hospitals. In this first German nationwide expert survey, we addressed the responsible university teaching coordinators in obstetrics and gynecology departments and investigated their experiences during the pandemic as well as their opinions on future developments, especially with regard to the broader implementation of e-learning in the standard curriculum. METHODS: The questionnaire included 42 items and was disseminated among teaching coordinators at all 41 departments of obstetrics and gynecology at German university hospitals via an email that included a weblink to the online survey provider. Responses were collected between 19 April and 7 June 2021. RESULTS: In total, 30 responses were collected from 41 departments across Germany and their respective teaching coordinators in obstetrics and gynecology. The general opinion of the medical teaching provided during the pandemic was positive, whereas the teaching quality in practical skills was considered inferior and not equivalent to the standard face-to-face curriculum. Lectures and seminars had to be substituted by remote-learning alternatives, while clinical clerkships were reduced in length and provided less patient contact. Students in their final year experienced only a few differences in the clinical and teaching routine. Teaching coordinators in obstetrics and gynecology stated that they intend to incorporate more e-learning into the curriculum in the future. CONCLUSION: The medical educators' views presented here may help to complement the already-thoroughly investigated experiences of students under the restrictions of the COVID-19 pandemic. Medical educators in obstetrics and gynecology at German university hospitals have successfully established online and hybrid teaching alternatives to their standard face-to-face courses. Building on recent experiences, digitalization could help to improve future medical education.
CRIS-Team Scopus Importer:2022-08-19

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.
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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 global pandemic and changes in women's reproductive health: an observational study - Haile, Liya; Van De Roemer, Niels; Gemzell-Danielsson, Kristina; Perello Capo, Josep; Lete Lasa, Inaki; Vannuccini, Silvia; Koch, Martin C.; Hildebrandt, Thomas; Calaf, Joaquim (European Journal of Contraception and Reproductive Health Care, 2022)
Objective The COVID-19 global pandemic has led to the death of millions around the world and impacted the overall health of many people. In this article we aim to compare reproductive health indicators in the first 6 months of 2020 to the prior year, as well as explore stress and quality of life during this time. Methods This retrospective observational study examined the menstrual cycles of 1159 women who were using a fertility tracking device to record their menstrual cycle and BBT data. We utilised a supplemental mobile application to administer a supplemental survey to collect data on stress and quality of life. Descriptive analyses were conducted with t-tests for two-group comparisons. Results Study participants from 15 countries contributed to a total of 13,194 cycles. 23.1% (268/1159) responded to the survey focussed on assessing psychosocial distress. 44.4% (119/268) of the study participants reported that they had noticed a change in their menstrual cycle, temperature curve, or menstruation in the past 12 months. Cycle analysis found the average cycle length and pre-ovulation phase length was longer in the first 6 months of 2019, while the average days of menstruation was slightly longer in 2020. Discussion Our findings indicate that menstrual cycle indicators changed only slightly in the first 6 months of 2020 but were still statistically significant. We were also able to understand that these study participants had some level of awareness of changes to their menstrual health.
CRIS-Team WoS Importer:2022-02-04

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 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 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.
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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.
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The Involvement of Cx43 in JNK1/2-Mediated Endothelial Mechanotransduction and Human Plaque Progression - Tauchi, Miyuki; Oshita, Kensuke; Urschel, Katharina; Furtmair, Roman; Kühn, Constanze; Stumpfe, Florian; Botos, Balazs; Achenbach, Stephan; Dietel, Barbara (International Journal of Molecular Sciences, 2023)
Atherosclerotic lesions preferentially develop at bifurcations, characterized by non-uniform shear stress (SS). The aim of this study was to investigate SS-induced endothelial activation, focusing on stress-regulated mitogen-activated protein kinases (MAPK) and downstream signaling, and its relation to gap junction proteins, Connexins (Cxs). Human umbilical vein endothelial cells were exposed to flow (“mechanical stimulation”) and stimulated with TNF-α (“inflammatory stimulation”). Phosphorylated levels of MAPKs (c-Jun N-terminal kinase (JNK1/2), extracellular signal-regulated kinase (ERK), and p38 kinase (p38K)) were quantified by flow cytometry, showing the activation of JNK1/2 and ERK. THP-1 cell adhesion under non-uniform SS was suppressed by the inhibition of JNK1/2, not of ERK. Immunofluorescence staining and quantitative real-time PCR demonstrated an induction of c-Jun and c-Fos and of Cx43 in endothelial cells by non-uniform SS, and the latter was abolished by JNK1/2 inhibition. Furthermore, plaque inflammation was analyzed in human carotid plaques (n = 40) using immunohistochemistry and quanti-gene RNA-assays, revealing elevated Cx43+ cell counts in vulnerable compared to stable plaques. Cx43+ cell burden in the plaque shoulder correlated with intraplaque neovascularization and lipid core size, while an inverse correlation was observed with fibrous cap thickness. Our results constitute the first report that JNK1/2 mediates Cx43 mechanoinduction in endothelial cells by atheroprone shear stress and that Cx43 is expressed in human carotid plaques. The correlation of Cx43+ cell counts with markers of plaque vulnerability implies its contribution to plaque progression.
CRIS-Team Scopus Importer:2023-02-03
Keywords: atherogenesis; endothelial dysfunction; gap junctions; MAPK; mechanotransduction; shear stress