Search

Background: Traumatic births not only cause emotional stress for expectant parents but can also affect the psychosocial health of midwives and obstetricians due to their professional demands., Aim: To evaluate the impact of traumatic birth experiences on the psychosocial health of obstetric healthcare professionals., Methods: A cross-sectional study using validated measurement tools (Impact of Event Scale Revised IES-R, Copenhagen Burnout Inventory CBI) and assessing post-traumatic growth (PGI-SF) through an online survey of midwives and obstetricians in German-speaking areas., Results: The study included 700 participants with peripartum and/or personal traumas. Of the 528 participants who completed the IES-R, 33 (6.3%) with post-traumatic stress disorder (PTSD) received less support from colleagues (p = 0.007) and were more likely to experience workplace consequences (p < 0.001) than participants without PTSD. A moderate to high level of burnout was found in 66.2% of the 542 participants who completed the CBI. Personal growth through experiencing trauma was reported by 75.9% of the 528 participants who completed the PGI-SF., Conclusion: The psychosocial health of midwives and obstetricians is at risk due to traumatic birth experiences. Screening tests and the provision of collegial and professional debriefings to strengthen resilience are essential preventive interventions., Competing Interests: Die Autorinnen/Autoren geben an, dass kein Interessenkonflikt besteht., (Thieme. All rights reserved.)

Purpose: More than a quarter of the German population has a migration background (MB). As various studies in the healthcare sector have already shown, ethnic background and migration status can have an influence on individual patient care. The aim of our study was to evaluate whether there are differences in utilization of out of pocket health-care services and the consultation situation in the context of prenatal care, taking into account migration status, acculturation and socio-demographic aspects., Methods: In the period from 01.03.21-01.03.22, a total of 511 women in childbed at the University Women's Hospital Ulm were interviewed in a retrospective survey using a standardized questionnaire translated into 9 languages and asked about their prenatal care. Due to the COVID pandemic, the study had to be terminated after one year., Results: Women with MB-particularly 1st generation migrant women-used significantly fewer out of pocket prenatal care services (p < 0.001) and felt less informed and counselled regarding costs and benefits of possible prenatal care examinations (p < 0.001) compared to women without MB. Consistent with these results, there were associations between the assimilation index (AI) of patients with MB and both utilization and perception of individual healthcare services., Conclusion: Our study indicates that even today there are still differences in the treatment and perception of various health services in the context of prenatal care between women with and those without MB., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: The current standard for the preoperative marking of non-palpable breast lesions is wire guided localization (WGL) which is associated with logistical efforts and patient discomfort. Non-radioactive seeds (NRS) recently challenged the use of WGL; but do they provide a better alternative from a logistical and environmental perspective?, Methods: WGL standard was compared with NRS available in Germany: Magseed®, Pintuition®, SAVI SCOUT ® and LOCalizer™ on a logistical and carbon-footprinting basis. In the logistical analysis the number of patient contacts with the healthcare system for lesion localization/removal and the number of breast punctures were evaluated in two different clinical scenarios (primary surgery and secondary surgery after neoadjuvant treatment). The carbon footprints of WGL and NRS (with exception of LOCalizer) were assessed based on their material compositions and operating energy in a streamlined approach., Results: Application of NRS reduces the number of contacts by 33.3 % (2 vs. 3) in primary, by 50 % (2 vs. 4) in secondary surgery, and the number of breast punctures by 33.3 % (2 vs.3). Annual Germany-wide material- and energy-based carbon footprints of NRS (1.6-3.2 tons CO 2 eq) are significantly lower in comparison to WGL (10.3 tons CO 2 eq). The implementation of NRS would lead to a CO 2 eq reduction by around 79 % compared to WGL., Conclusions: The use of NRS for the localization of non palpable breast lesions is more favorable from the environmental and logistical perspective, when compared to WGL with possible benefits for patients, healthcare providers and the environment., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Thorsten Kuehn reports a relationship with Merit Medical Systems, Hologic, Sirius Medical Systems, and Endomag that includes: consulting or advisory and speaking and lecture fees. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Purpose: To summarize the radiotherapy-relevant statements of the 18th St. Gallen Breast Cancer Consensus Conference and interpret the findings in light of German guideline recommendations., Methods: Statements and voting results from the 18th St. Gallen International Breast Cancer Consensus Conference were collected and analyzed according to their relevance for the radiation oncology community. The voting results were discussed in two hybrid meetings among the authors of this manuscript on March 18 and 19, 2023, in light of the German S3 guideline and the 2023 version of the Arbeitsgemeinschaft Gynäkologische Onkologie (AGO) guidelines., Results and Conclusion: There was a high level of agreement between the radiotherapy-related statements of the 18th St. Gallen International Breast Cancer Consensus Conference and the German S3 and AGO guidelines. Discrepancies include the impact of number of lymph node metastases for the indication for postmastectomy radiotherapy., (© 2024. The Author(s).)

Purpose: This study examined the pattern of psychosocial care in breast cancer survivors., Methods: In a prospective study with measurements before surgery, 1 month, 8 months, and 5 years thereafter, we examined the proportion of breast cancer survivors who were aware about, had been offered and received various types of psychosocial services from psychologists, social workers, doctors, self-help groups etc. The degree of helpfulness per service among users was ascertained with Likert scales. Determinants of awareness, offer and use were investigated using binary logistic regression analyses. How the services are inter-related was tested with principal component analyses., Results: Among 456 breast cancer survivors who participated until 5 years, psychological services were known by 91%, offered to 68%, and used by 55% of patients. Social services were known by 86%, offered to 65%, and used by 51%. Women ≥ 65 years were less likely to be informed about (odds ratio (OR) 0.2) and get offers for psychosocial services (OR 0.4 for social and 0.5 for psychological services) than women < 65 years. The services rated most helpful were social services in the hospital, psychological counselling by a consultant and psychotherapy in private practices., Conclusion: These findings underline the importance of psychosocial support by physicians in addition to the "professional" mental health and social care providers. They also show that elderly women in need for support might be in danger of not being well-informed about the services available., (© 2022. The Author(s).)

Purpose: We aimed to explore the trajectory of financial difficulties among breast cancer survivors in the German health system and its association with migration background., Methods: In a multicentre prospective study, breast cancer survivors were approached four times (before surgery, before and after adjuvant therapy, five years after surgery) and asked about their migration history and financial difficulties. Migrants were defined as born/resided outside Germany or having citizenship/nationality other than German. Financial difficulties were ascertained with the financial difficulties item of the European Organisation for Research and Treatment of Cancer Core Instrument (EORTC QLQ-C30) at each time-point (cut-off > 17). Financial difficulties were classified in trajectories: always (every time-point), never (no time-point), initial (first, not fourth), delayed (only fourth), and acquired (second and/or third, not first). A logistic regression was conducted with the trajectories of financial difficulties as outcome and migration background as exposure. Age, trends in partnership status, and educational level were considered as confounders., Results: Of the 363 participants included, 49% reported financial difficulties at at least one time-point. Financial difficulties were reported always by 7% of the participants, initially by 5%, delayed by 10%, and acquired by 21%. Migrants were almost four times more likely to report delayed (odds ratio [OR] = 3.7; 95% confidence interval [CI] 1.3, 10.5) or acquired (OR = 3.6; 95% CI 1.6, 8.4) financial difficulties compared to non-migrant participants., Conclusion: Survivors with a migration background are more likely to suffer from financial difficulties, especially in later stages of the follow-up. A linguistically/culturally competent active enquiry about financial difficulties and information material regarding supporting services/insurances should be considered., (© 2022. The Author(s).)

Purpose: Radiotherapy (RT) was identified as a risk factor for long-term cardiac effects in breast cancer patients treated until the 1990s. However, modern techniques reduce radiation exposure of the heart, but some exposure remains unavoidable. In a retrospective cohort study, we investigated cardiac mortality and morbidity of breast cancer survivors treated with recent RT in Germany., Methods: A total of 11,982 breast cancer patients treated between 1998 and 2008 were included. A mortality follow-up was conducted until 06/2018. In order to assess cardiac morbidity occurring after breast cancer treatment, a questionnaire was sent out in 2014 and 2019. The effect of breast cancer laterality on cardiac mortality and morbidity was investigated as a proxy for radiation exposure. We used Cox Proportional Hazards regression analysis, taking potential confounders into account., Results: After a median follow-up time of 11.1 years, there was no significant association of tumor laterality with cardiac mortality in irradiated patients (hazard ratio (HR) for left-sided versus right-sided tumor 1.09; 95% confidence interval (CI) 0.85-1.41). Furthermore, tumor laterality was not identified as a significant risk factor for cardiac morbidity (HR = 1.05; 95%CI 0.88-1.25)., Conclusions: Even though RT for left-sided breast cancer on average incurs higher radiation dose to the heart than RT for right-sided tumors, we found no evidence that laterality is a strong risk factor for cardiac disease after contemporary RT. However, larger sample sizes, longer follow-up, detailed information on individual risk factors and heart dose are needed to assess clinically manifest late effects of current cancer therapy., (© 2021. The Author(s).)

Background: The GAIN-2 trial was designed to identify a superior intense dose-dense (idd) strategy for high-risk patients with early breast cancer. Here, we report an interim analysis, at which the predefined futility boundary was crossed., Patients and Methods: GAIN-2 was an open-label, randomised, multicentre phase III trial. Two thousand eight hundred and eighty seven patients were randomised 1:1 between three courses each of idd epirubicin (E) 150 mg/m 2 , nab-paclitaxel (nP) 330 mg/m 2 and cyclophosphamide (C) 2000 mg/m 2 (iddEnPC) versus four cycles of leucocyte nadir-based tailored and dose-dense EC (dtEC) followed by four cycles of tailored and dose-dense docetaxel (dtD) (dtEC-dtD)., Results: The duration of median follow-up was 45.8 (range 0.0-88.3) months. Trial objectives included invasive disease-free survival (iDFS) as the primary end-point. A total of 593 patients received the treatment as neoadjuvant chemotherapy. At the time of futility interim analysis, 414 events for iDFS were reported. Overall, there was no difference in iDFS between iddEnPC and dtEC-dtD with 4-year iDFS rates of 84.3% (95% confidence interval (CI) 82.0-86.4%). Among all predefined subgroups, hormone receptor-positive and human epidermal growth factor receptor 2-negative (HR+/HER2-), lobular cancer and ≤50 years subgroups predicted for better iDFS in the dtEC-dtD arm. Overall, 88.1% of patients completed all treatment in both arms. Haematological toxicity grade 3/4 and grade 3/4 non-haematological adverse events were significantly higher with iddEnPC (iddEnPC 50.8% vs dtEC-dtD 45.1%, P = 0.002), especially arthralgia and peripheral sensory neuropathy. Two treatment-related deaths occurred during dtEC-dtD, corresponding to a low mortality rate of 0.07%., Conclusions: iDFS is equal in both regimens, but tailoring dose-dense chemotherapy improved outcomes in HR+/HER2-, lobular cancer and patients ≤50 years., Competing Interests: Conflict of interest statement The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: AS reports grants from Celgene, grants from Roche, grants from AbbVie, personal fees from Roche, personal fees from AstraZeneca, personal fees from Celgene, personal fees from Roche, personal fees from Roche, personal fees from Celgene, personal fees from Pfizer, personal fees from AstraZeneca, personal fees from Novartis, personal fees from MSD, personal fees from Tesaro, personal fees from Lilly, personal fees from Pfizer, other from Roche, outside the submitted work; CD reports personal fees from Novartis, Roche, MSD Oncology, Daiichi Sankyo, grants from Myriad Genetics, other from Sividon Diagnostics/Myriad, outside the submitted work and has a patent EP18209672 pending, a patent EP20150702464 pending and a patent Software (VMscope digital pathology) pending. CJ reports honoraria from Roche, Celgene, Novartis, Genomic Health and Amgen; compensation for consulting and advisory role from Roche, Novartis and Pfizer; travel expenses from Roche, Astra Zeneca and Genomic Health; CS reports compensation for consulting and advisory role from Olympus, Hologic; and travel expenses from imed, MedConcept, Medtronic, Diaglog Service, Mentor, mylan, GBG and Pfizer; ES reports honoraria from Roche, Astra Zeneca, Novartis, Pfizer, ESAI, Tesaro and MSD; compensation for consulting and advisory role from Roche and Tesaro; and travel expenses from Roche and Pfizer; FM reports personal fees from Roche, AstraZeneca, Pfizer, Tesaro, Novartis, Amgen, PharmaMar, GenomicHealth, CureVac, EISAI, Celgene, Clovis, Janssen-Cilag, Immunomedics, GSK, MSD, Seagen and Lilly outside the submitted work; JH reports grants and personal fees from Novartis, personal fees from Lilly, personal fees and other from Pfizer, personal fees and other from Roche, personal fees from Abbvie, personal fees from Astra Zeneca, personal fees from Eisai, other from Daichii, grants, personal fees and other from Celgene, personal fees from MSD, grants and personal fees from Hexal, outside the submitted work; JUB reports personal fees from AMGEN, personal fees from ASTRA Zeneca, personal fees from Novartis, personal fees from Pfizer, personal fees from Roche, personal fees from SonoScape, from Sysmex, outside the submitted work; MR reports honoraria from MSD, Astra Zeneca, Lilly, Novartis and SOMATEX; compensation for consulting and advisory role from Roche, Novartis, MSD, Astra Zeneca and Lilly; and travel expenses from Pfizer, Novartis and Celgene; MU reports honoraria paid to his employer by Amgen, Astra Zeneca, Celgene, Daiji Sankyo, Eisai, Lilly, MSD, Mundipharma, Pfizer, Novartis, Roche, Sanofi Aventis and PUMA Biotechnology; compensation for consulting and advisory role to the employer from Amgen, Abbvie, Astra Zeneca, Celgene, Daiji Sankyo, Eisai, Lilly, MSD, Mundipharma, Novartis, Odonate, Pfizer, Roche, PUMA Biotechnology, Sanofi Aventis and Teva; SL reports grants and other from Roche during the conduct of the study; grants and other from Abbvie, grants and other from Amgen, grants and other from Celgene, grants and non-financial support from Immunomedics, grants and other from Novartis, grants and other from Pfizer, other from Seattle Genetics, other from PriME/Medscape, personal fees from Chugai, grants from Teva, grants from Vifor, grants and other from Daiichi-Sankyo, other from Lilly, other from Samsung, other from EirGenix, other from BMS, other from Puma, other from MSD and grants and other from AstraZeneca outside the submitted work; In addition, SL has a patent EP14153692.0 pending. TL reports honoraria from Lilly, Teva, Tesaro, Roche, Novartis, Pfizer, MSD, Amgen and Clovis; compensation for consulting and advisory role from Lilly, Roche, Tesaro, Amgen and MSD; travel expenses from Roche, Pfizer and Celgene; VM reports speaker honoraria from Amgen, Astra Zeneca, Celgene, Roche, TEVA and consultancy honoraria from Roche, Amgen, Tesaro and Myelo Therapeutics; WJ reports grants and personal fees from Sanofi-Aventis, Novartis, Lilly, Pfizer, Roche, Chugai and AstraZeneca during the conduct of the study; No other potential conflict of interest relevant to this article was reported., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Purpose: Obstetric anal sphincter injuries (OASIS) increase the risk for pelvic floor dysfunctions. The goal of this study was to examine the long-term outcomes after OASIS on pelvic floor functions and quality of life., Material and Methods: Between 2005 and 2013, 424 women had an OASIS at the Women University Hospital Ulm. Out of these 71 women completed the German pelvic floor questionnaire, which includes questions regarding prolapse symptoms as well as bladder, bowel and sexual function. In addition, 64 women were physically examined, including a speculum examination to evaluate the degree of prolapse, a cough test to evaluate urinary stress incontinence (SI) and an evaluation of both pelvic floor sphincter (modified Oxford score) and anal sphincter contraction., Results: A high rate of pelvic floor disorders after OASIS was found, as 74.6% of women reported SI, 64.8% flatus incontinence and 18.3% stool incontinence, respectively. However, only few women stated a substantial negative impact on quality of life. The clinical examination showed that a positive cough test, a weak anal sphincter tone and a diagnosed prolapse correlated with the results of the self-reported questionnaire., Conclusion: On one hand, OASIS has an influence on pelvic floor function going along with lots of complaints, while on the other hand, it still seems to be a taboo topic, as none of the participants spoke about the complaints after OASIS with a doctor. Therefore, the gynecologist should actively address these issues and offer therapy options for the women with persisting problems.

Introduction: Ki67 as a proliferative marker has prognostic and therapeutic relevance in early breast cancer (EBC). However, standard cutoffs for distinguishing low and high Ki67 do not exist., Material and Methods: Data from all patients treated at the University Hospital Ulm for EBC between January 2013 and December 2015 with documented results for internal Ki67 assessment of the primary (n = 917) tumor were retrospectively analyzed evaluating the associations between Ki67 and other clinicopathological factors., Results: 595 (64.9%) patients had a Ki67 <20% and 322 (35.1%) a Ki67 ≥20%. The median Ki67 was 10% (range 1-90%). Median Ki67 values according to the hormone receptor (HR)/ human epidermal growth factor receptor 2 (HER2) subtypes were 10% for HR-positive/HER2 negative (HR+/HER2-) disease (n = 717), 20% for HR+/HER2+ (n = 76), 30% for HR-/HER2+ (n = 45), and 60% for HR-/HER2- (n = 75). 75.2% or 89.3% of all patients with HER2-positive or triple-negative disease had a Ki67 ≥20%, respectively. Using a multivariable logistic regression with Ki67 (<20% vs. ≥20%) as binary dependent variable, younger age, positive nodal status, higher grading, histological nonspecific type carcinoma, negative HR status, and positive HER2 status were shown to be significantly associated with a higher proliferative index (Ki67 ≥20%)., Conclusion: This analysis described Ki67 in different subtypes in EBC and its association with clinicopathological factors. According to more aggressive tumor biology, the respective subgroups also showed higher median Ki67 levels. However, definition of low and high proliferation index itself is difficult. It is essential to interpret Ki67 indices carefully with regard to the own institutional values and other clinicopathological factors., (© 2021 S. Karger AG, Basel.)

Purpose: Treatment with CDK4/6 inhibitors and endocrine therapy (CDK4/6i + ET) is a standard for patients with advanced hormone receptor-positive, HER2-negative (HR + HER2-) breast cancer (BC). However, real-world data on the implementation of therapy usage, efficacy, and toxicity have not yet been reported., Methods: The PRAEGNANT registry was used to identify advanced HR + HER2- BC patients (n = 1136). The use of chemotherapy, ET, everolimus + ET, and CDK4/6i + ET was analyzed for first-line, second-line, and third-line therapy. Progression-free survival (PFS) and overall survival (OS) were also compared between patients treated with CDK4/6i + ET and ET monotherapy. Also toxicity was assessed., Results: CDK4/6i + ET use increased from 38.5% to 62.7% in the first 2 years after CDK4/6i treatment became available (November 2016). Chemotherapy and ET monotherapy use decreased from 2015 to 2018 from 42.2% to 27.2% and from 53% to 9.5%, respectively. In this early analysis no statistically significant differences were found comparing CDK4/6i + ET and ET monotherapy patients with regard to PFS and OS. Leukopenia was was seen in 11.3% of patients under CDK4/6i + ET and 0.5% under ET monotherapy., Conclusions: In clinical practice, CDK4/6i + ET has been rapidly implemented. A group of patients with a more unfavorable prognosis was possibly treated in the real-world setting than in the reported randomized clinical trials. The available data suggest that longer follow-up times and a larger sample size are required in order to identify differences in survival outcomes. Studies should be supported that investigate whether chemotherapy can be avoided or delayed in this patient population by using CDK4/6i + ET., Competing Interests: Declaration of competing interest A.S. received honoraria from Roche, AstraZeneca, Aurikamed GmbH, Celgene, ClinSol Research GmbH, Connectmedica Sp.Z o.o., Deutsche Gesellschaft für Senologie GmbH, if-kongress management gmbh, I-MED Institute GmbH, Lilly Deutschland GmbH, Medicultus GmbH, med publico GmbH, MSD Sharp & Dohme GmbH, onkowissen.de GmbH, Pfizer GmbH, Schattauer Verlag GmbH, Promedicis GmbH, Tesaro Bio Germany GmbH, W. Zuckschwerdt Verlag GmbH. J.E. received honoraria from AstraZeneca, Celgene, Novartis, Lilly, Pfizer, Pierre Fabre, Roche and TEVA and travel support from Celgene, Pfizer, TEVA, and Pierre Fabre. D.L. received honoraria from Amgen, AstraZeneca, Celgene, Lilly, Loreal, MSD, Novartis, Pfizer, Tesaro, Teva. M.W.B reports support from Novartis, Merck Sharp & Dohme, AstraZeneca, Roche, Amgen, Eisai, paid to his institution. E.B. received honoraria from Novartis, Celgene, Riemser, Pfizer, Hexal, Amgen, onkowissen.de for consulting, clinical research management or medical education activities. P.A.F. received honoraria from Novartis, Pfizer, Roche, Amgen, Celgene, Daiichi-Sankyo, AstraZeneca, Merck-Sharp & Dohme, Eisai, Puma and Teva. His institution conducts research with funding from Novartis and Biontech. T.N.F. reports personal fees from Roche, personal fees from Novartis, personal fees from Pfizer, personal fees from Daichii Sankyo, personal fees from Lilly, personal fees from MSD, outside the submitted work. P.H. received honoraria, unrestricted educational grants and research funding from Amgen, AstraZeneca, Eli Lilly, MSD, Novartis, Pfizer, and Roche. A.D.H. received honoraria from Teva, GenomicHealth, Celgene, AstraZeneca, Novartis, Pfizer, and Roche. C.H. received honoraria from Amgen, Celgene, Oncovis, Roche, and Pfizer. J.H. received honoraria from Astra Zeneca, MSD, Lilly, travel grants from Novartis and research grants from Novartis, Celgene. E.R. reports personal fees from Roche, Pfizer, Amgen, Novartis, Tesaro, Astra Zeneca, Celgene, Pierre Fabre and Riemer, non-financial support from Olympus GmbH, personal fees from Riemser, outside the submitted work. W.J. received research grants and honoroaria from Novartis, Pfizer, Amgen, Chugai, Roche, Genomic-Health, AstraZeneca, Lilly. H.-C.K. received honoraria from Carl Zeiss meditec, TEVA, Theraclion, Novartis, Amgen, AstraZeneca, Pfizer, Janssen-Cilag, GSK, LIV Pharma, and Genomic Health. C.M.K. received honoraria from Amgen, Axios, Roche, Teva, Novartis, MSD Sharp & Dohme, Mundipharma, NewCo, Pfizer, Riemser, and ZytoService, research grants from Amgen, Axios, Novartis, MSD Sharp & Dohme, NewCo, Pfizer, and ZytoService, and travel support from Amgen, Paxman Inc., PharmaMar, and Pfizer. M.P.L. has participated on advisory boards for AstraZeneca, MSD, Novartis, Pfizer, Eisai, Genomic Health, Tesaro and Roche and has received honoraria for lectures from MSD, Lilly, Roche, Novartis, Pfizer, Genomic Health, AstraZeneca, medac and Eisai. V.M. received speaker honoraria from Amgen, Astra Zeneca, Celgene, Daiichi-Sankyo, Eisai, Pfizer, Novartis, Roche, Teva, Janssen-Cilag and consultancy honoraria from Genomic Health, Hexal, Roche, Pierre Fabre, Amgen, Novartis, MSD, Daiichi-Sankyo, Eisai, Lilly, Tesaro and Nektar. N.N. received consultancy honoraria from Janssen-Cilag and travel support from Novartis. F.O. received speaker and consultancy honoraria from Amgen, AstraZeneca, Bayer, BMS, Boehringer, Celgene, Cellex, Chugai, Gilead, Hexal, Ipsen, Janssen-Cilag, Merck, MSD, Novartis, Riemser, Roche, Tesaro, Teva. H.T. received honoraria from Novartis, Roche, Celgene, TEVA, and Pfizer and travel support. F.-A. T. received honoraria from Astra Zeneca, Genomic Health and Novartis. C.T. received honoraria from Amgen, Astra-Zeneca, Celgene, Novartis, Pfizer, and Roche. M.U. reports support paid to his institution from Abbvie, Amgen GmbH München, Astra Zeneca, BMS, Celgene GmbH München, Daiji Sankyo, Eisai GmbH München, Janssen Cilag, Johnsen&Johnsen, Lilly Deutschland, Lilly Int., MSD Merck, Mundipharma, Myriad Genetics GmbH Zürich, Odonate, Pfizer GmbH Berlin, PUMA Biotechnology, Riemser, Roche Pharma AG, Grenzach Wyhlen, Sanofi Aventis Deutschland GmbH, Sividon Diagnostics Köln, TEVA Pharmaceuticals Ind. Ltd. und. Berlin(.)P.W. received honoraria from Amgen, AstraZeneca, Merck Sharp & Dohme, Novartis, Pfizer, PharmaMar, Roche, TEVA, Eisai Clovis and Tesaro. She participated in advisory boards of Amgen, AstraZeneca, Merck Sharp & Dohme, Novartis, Pfizer, PharmaMar, Roche, TEVA, Eisai Clovis and Tesaro. Her institution received research grants from Amgen, AstraZeneca, MSD, Novartis, Pfizer, Pharmamar, Clovis and Tesaro. R.W. received honoraria from Agendia, Amgen, Astra Zeneca, Boeringer Ingelheim, Carl Zeiss, Celgene, Daiichi-Sankyo, Esai, Genomic Health, Glaxo Smith Kline, Lilly, MSD, Mundipharma, Nanostring, Novartis, Odonate, Paxman, Palleos, Pfizer, Pierre Fabre, PumaBiotechnolgogy, Riemser, Roche, Sandoz/Hexal, Seattle Genetics, Tesaro Bio, Teva. M.W. received speaker honoraria from AstraZeneca, Celgene, and Novartis. S.Y.B. reports personal fees from Novartis and Pfizer, both outside the submitted work. All remaining authors (J.S., E.K., M.G., L.H., B.V., D.W.) have declared that they do not have any conflicts of interest., (Copyright © 2020 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Eligibility criteria are a critical part of clinical trials, as they define the patient population under investigation. Besides certain patient characteristics, clinical trials often include biomarker testing for eligibility. However, patient-identification mostly relies on the trial site itself and is often a time-consuming procedure, which could result in missing out on potentially eligible patients. Pre-selection of those patients using a registry could facilitate the process of eligibility testing and increase the number of identified patients. One aim with the PRAEGNANT registry (NCT02338167) is to identify patients for therapies based on clinical and molecular data. Here, we report eligibility testing for the SHERBOC trial using the German PRAEGNANT registry., Methods: Heregulin (HRG) has been reported to identify patients with better responses to therapy with the anti-HER3 monoclonal antibody seribantumab (MM-121). The SHERBOC trial investigated adding seribantumab (MM-121) to standard therapy in patients with advanced HER2-negative, hormone receptor-positive (HR-positive) breast cancer and HRG overexpression. The PRAEGNANT registry was used for identification and tumor testing, helping to link potential HRG positive patients to the trial. Patients enrolled in PRAEGNANT have invasive and metastatic or locally advanced, inoperable breast cancer. Patients eligible for SHERBOC were identified by using the registry. Study aims were to describe the HRG positivity rate, screening procedures, and patient characteristics associated with inclusion and exclusion criteria., Results: Among 2769 unselected advanced breast cancer patients, 650 were HER2-negative, HR-positive and currently receiving first- or second-line treatment, thus potentially eligible for SHERBOC at the end of current treatment; 125 patients also met further clinical eligibility criteria (e.g. menopausal status, ECOG). In the first/second treatment lines, patients selected for SHERBOC based on further eligibility criteria had a more favorable prognosis than those not selected. HRG status was tested in 38 patients, 14 of whom (36.8%) proved to be HRG-positive., Conclusion: Using a real-world breast cancer registry allowed identification of potentially eligible patients for SHERBOC focusing on patients with HER3 overexpressing, HR-positive, HER2-negative metastatic breast cancer. This approach may provide insights into differences between patients eligible or non-eligible for clinical trials., Trial Registration: Clinicaltrials, NCT02338167 , Registered 14 January 2015 - retrospectively registered.

Background: Patients with breast cancer (BC) show strong interest in complementary and alternative medicine (CAM), particularly for adverse effects of adjuvant endocrine treatment - e.g., with letrozole. Letrozole often induces myalgia/limb pain and arthralgia, with potential noncompliance and treatment termination. This analysis investigated whether CAM before aromatase inhibitor (AI) therapy is associated with pain development and the intensity of AI-induced musculoskeletal syndrome (AIMSS) during the first year of treatment., Patients and Methods: The multicenter phase IV PreFace study evaluated letrozole therapy in postmenopausal, hormone receptor-positive patients with early BC. Patients were asked about CAM use before, 6 months after, and 12 months after treatment started. They recorded pain every month for 1 year in a diary including questions about pain and numeric pain rating scales. Data were analyzed for patients who provided pain information for all time points., Results: Of 1396 patients included, 901 (64.5%) had used CAM before AI treatment. Throughout the observation period, patients with CAM before AI treatment had higher pain values, for both myalgia/limb pain and arthralgia, than non-users. Pain increased significantly in both groups over time, with the largest increase during the first 6 months. No significant difference of pain increase was noted regarding CAM use., Conclusions: CAM use does not prevent or improve the development of AIMSS. Pain intensity was generally greater in the CAM group. Therefore, because of the risk of non-compliance and treatment discontinuation due to the development of higher pain levels, special attention must be paid to patient education and aftercare in these patients., Competing Interests: Declaration of competing interest S·Y.B. has received honoraria from Pfizer and Novartis. W.J. has received honoraria and research grants from Novartis. A.D.H. has received honoraria from AstraZeneca, Genomic Health, Roche, Novartis, Celgene, and Pfizer. R.W. has received honoraria and research funds from Novartis. S.K. has received honoraria from Roche, Celgene, Amgen, and AstraZeneca and funding support from Roche. C.T. has received honoraria from Novartis, Pfizer, and AstraZeneca. M.P.L. has participated on advisory boards for AstraZeneca, MSD, Novartis, Pfizer, Genomic Health, and Roche and has received honoraria for lectures from Lilly, Roche, Novartis, Pfizer, Genomic Health, AstraZeneca, medac, and Eisai. P.G. has received honoraria from Novartis and financial support for symposia from Novartis, Roche, and PharmaMar. H.-C.K. has received honoraria from Carl Zeiss meditec, TEVA, Theraclion, Novartis, Amgen, Astra Zeneca, Pfizer, Janssen-Cilag, GSK, LIV Pharma, Roche, and Genomic Health. D.S.-B. has received honoraria from Novartis. M.W.B.‘s institution has received research grants from Novartis. T.F. has received honoraria from Pfizer, Novartis, Roche, and Amgen. P.A.F. has received honoraria from Roche, Pfizer, Novartis, and Celgene. His institution conducts research for Novartis. N.N. has received honoraria from Janssen-Cilag, Novartis and Teva. All of the remaining authors have declared that they have no conflicts of interest., (Copyright © 2020 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background Peripartal hysterectomy (PH) is a challenging surgical procedure with elevated maternal morbidity. Methods From 2004 to 2016, 41 emergency PHs were performed at the tertiary care center of the Department of Gynecology and Obstetrics at University Hospital Ulm. In our retrospective analysis, the incidence of PH in our hospital was 12.8 per 10,000 deliveries with a maternal mortality of 2.4%. PH followed in 80.5% after cesarean section (c-section). Underlying causes/indications for PH were abnormal placentation (53.7%; n=22), uterine atony (26.8%; n=11), uterine lacerations (14.6%; n=6) and in rare cases uterine infection (4.9%; n=2). The median number of transfused products was 11 packed red blood cells (range 0-55 products), 10 fresh frozen plasma units (range 1-43) and two platelet concentrates (0-16). Results Loss of blood as estimated by surgeons was significantly correlated with actual transfused blood volume (P<0.001). Clinically relevant intra- and/or postoperative complications occurred in 53.7% of patients (n=22). Abnormal placentation was the leading cause for PH with an increased incidence during the last 10 years presumptively representing the elevated rate of c-sections. Conclusion PH goes along with increased rates of blood product transfusions independently of indication for surgery and has a high morbidity with a major complication rate of more than 50%. Prepartal assessment of risk factors like abnormal invasive placenta are crucial for reducing maternal morbidity.

Background: Endocrine treatment (ET) with an aromatase inhibitor (AI) is the treatment of choice in post-menopausal patients with hormone receptor-positive early breast cancer (EBC). However, adverse events (AEs) often lead to treatment discontinuation. This analysis aimed to identify side-effects that lead to patients failing to persist with letrozole treatment., Patients and Methods: Post-menopausal hormone receptor-positive EBC patients starting ET with letrozole were enroled in EvAluate-TM, a non-interventional study. Information regarding treatment compliance and persistence was gathered in months 6 and 12. Persistence was defined as the time from 30 d after the start to the end of treatment. The influence on persistence of musculoskeletal syndrome, menopausal disorder, sleep disorder and other AEs within the first 30 d was analysed using Cox regression analyses., Results: Among 3887 patients analysed, the persistence rate after 12 months was >85%. In all, 568 patients (14.6%) discontinued the treatment, 358 of whom (63.0%) did so only because of side-effects. The main AEs influencing persistence were musculoskeletal symptoms (hazard ratio [HR] 2.55; 95% confidence interval [CI], 1.90-3.42), sleep disorders (HR 1.95; 95% CI, 1.41-2.70) and other AEs (HR 2.03; 95% CI, 1.51-2.73). Menopausal disorder was not associated with non-persistence (HR 1.17; 95% CI, 0.74-1.84)., Conclusions: These results suggest that side-effects of AIs such as musculoskeletal syndrome and sleep disorder lead to ET discontinuation within the first treatment year in significant numbers of EBC patients. Compliance programmes adapted for subgroups that are at risk for early non-persistence might help to ensure the recommended therapy duration., Clinical Trials Number: CFEM345DDE19., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Background: Breast cancer is the most common cancer in women. The German S3 guideline of 2012 has now been updated to take account of advances in the early detection, diagnostic evaluation, treatment, and follow-up care of this disease., Methods: The updating process was based on the adaptation of identified source guidelines and on reviews of the scientific evidence. A systematic search in multiple literature databases was carried out, and the full texts of the selected articles were evaluated. Suggested recommendations were then proposed by interdisciplinary working groups and modified and graded in a nominal consensus procedure., Results: The value of mammographic screening is confirmed in the updated guideline. As for the diagnostic evaluation of breast cancer, computed tomography is recommended for staging in patients with a high risk of recurrence, in addition to conventional methods. As for surgical treatment, the evidence supporting locoregional surgery for primary breast cancer now affords an opportunity for de-escalation: complete resection yields the best outcome, but a safety margin of several millimeters is not necessary. Axillary dissection is no longer recommended except in certain defined situations. Radiotherapeutic approaches consist of hypofractionated applications. Adjuvant systemic therapy is indicated for patients in certain high-risk situations defined by a constellation of factors including tumor grade, patient age, node status, Ki-67 antigen expression, hormone receptor status, and human epidermal growth factor receptor 2 (HER2) status. All patients with hormone receptor-positive breast cancer should receive endocrine therapy. The indication for chemotherapy and/or anti-HER2 therapy should be determined in consideration of the expected benefit and side effects., Conclusion: Consistent implementation of the recommendations in the newly updated guideline can help lessen morbidity and mortality from breast cancer. The actual extent to which breast cancer guidelines are implemented should be a topic of future research.

Background: Approximately one-third of all women of childbearing age are overweight or obese. For these women, pregnancy is associated with increased risks for both mother and child., Methods: This review is based on pertinent publications retrieved by a selective search of PubMed, with special attention to current population-based cohort studies, systematic reviews, meta-analyses, and controlled trials., Results: Obesity in pregnancy is associated with unfavorable clinical outcomes for both mother and child. Many of the risks have been found to depend linearly on the body-mass index (BMI). The probability of conception declines linearly, starting from a BMI of 29 kg/m2, by 4% for each additional 1 kg/m2 of BMI (hazard ratio 0.96, 95% confidence interval: [0.91; 0.99]). A 10% increase of pregravid BMI increases the relative risk of gestational diabetes and that of preeclampsia by approximately 10% each. A 5 kg/m2 increase of BMI elevates the relative risk of intrauterine death to 1.24 [1.18; 1.30]. An estimated 11% of all neonatal deaths can be attributed to the consequences of maternal overweight and obesity. Nonetheless, in most randomized controlled trials, nutritional and lifestyle interventions did not bring about any clinically relevant reduction in the incidence of gestational diabetes and fetal macrosomia., Conclusion: The risks associated with obesity in pregnancy cannot necessarily be influenced by intervention. Preventive measures aimed at normalizing body weight before a woman becomes pregnant are, therefore, all the more important.

Background: In addition to established prognostic factors, individual lifestyle-associated factors, such as obesity, physical activity, and diet, seem to modulate the course of breast cancer. The aim of this analysis was to evaluate the influence of weight changes during adjuvant chemotherapy on outcome in a large multicenter prospectively randomized trial., Patients and Methods: The ADEBAR trial compares a sequential chemotherapy consisting of epirubicin/cyclophosphamide followed by docetaxel to an epirubicin/5-fluorouracil/cyclophosphamide regimen in patients with lymph node-positive early breast cancer. Body weight was measured before each cycle of chemotherapy. According to the relative weight change (≥ 5%) between the first and the last cycle, patients were categorized into the weight gain, weight loss, or stable weight group. Overall survival (OS) and disease-free survival were assessed by univariate Kaplan-Meier and multivariate Cox regression analyses., Results: Concise data from 1080 of 1493 participants who completed all cycles of chemotherapy were available for analysis. Of 307 patients (24.8%) whose weight changed by ≥ 5%, 120 patients (11.1%) lost and 187 (17.3%) gained weight. Multivariate analysis showed a significant independent effect of weight change on OS (P = .039), but not on disease-free survival (P = .111). Both weight change groups had a worse OS compared to patients with stable weight (weight gain: hazard ratio, 1.55; 95% confidence interval, 1.01-2.40; P = .047; weight loss: hazard ratio, 1.55; 95% CI, 0.97-2.47; P = .067)., Conclusion: Weight change of > 5% during adjuvant chemotherapy in patients with high-risk early breast cancer is associated with poor OS., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Purpose: Our aim was to implement a structured literature search using PICO (patient/intervention/comparison/outcome) questions and a standardized consensus method for the German Guideline 'Detection, diagnostics, therapy and follow-up of Breast Cancer' using, as an example, the significance of systemic therapy in lymph node recurrent disease (LNRD)., Methods: We defined specified PICO questions according to the clinical significance of a recommendation for systemic therapies in locoregional LNRD. A methodologist performed a systematic literature search including randomized controlled trials, systematic reviews and observational studies (2007-2016). In a consensus conference, the level of evidence and consensus was determined and the clinical recommendation was adopted., Results: In total 143 publications were identified according to the search strategy including 14 duplicates, which were excluded. 4 publications were included based on experts' choice. The team excluded 119 publications, leaving 14 that were then screened by a full text search. Finally, 1 publication was found to be of methodologically and clinically reliable content. The conclusion of this publication in favor of systemic therapy for LNRD received strong consent from the consensus conference., Conclusions: The literature search strategy using PICO questions helped to achieve a fast and standardized selection of publications. The recommendation concerning systemic treatment of LNRD was first implemented in the update of the German Breast Cancer guideline., (© 2018 S. Karger GmbH, Freiburg.)

The purpose of this retrospective multicenter study was to resolve the pseudo-paradox that the clinical outcome of women affected by breast cancer has improved during the last 20 years irrespective of whether they were treated in accordance with clinical guidelines or not. This retrospective German multicenter study included 9061 patients with primary breast cancer recruited from 1991 to 2009. We formed subgroups for the time intervals 1991-2000 (TI1) and 2001-2009 (TI2). In these subgroups, the risk of recurrence (RFS) and overall survival (OS) were compared between patients whose treatment was either 100% guideline-conforming or, respectively, non-guideline-conforming. The clinical outcome of all patients significantly improved in TI2 compared to TI1 [RFS: p < 0.001, HR = 0.57, 95% CI (0.49-0.67); OS: p < 0.001, HR = 0.76, 95% (CI 0.66-0.87)]. OS and RFS of guideline non-adherent patients also improved in TI2 compared to TI. Comparing risk profiles, determined by Nottingham Prognostic Score reveals a significant (p = 0.001) enhancement in the time cohort TI2. Furthermore, the percentage of guideline-conforming systemic therapy (endocrine therapy and chemotherapy) significantly increased (p < 0.001) in the time cohort TI2 to TI for the non-adherent group. The general improvement of clinical outcome of patients during the last 20 years is also valid in the subgroup of women who received treatments, which deviated from the guidelines. The shift in risk profiles as well as medical advances are major reasons for this improvement. Nevertheless, patients with 100% guideline-conforming therapy always had a better outcome compared to patients with guideline non-adherent therapy.

Purpose: The tumor biology of older breast cancer patients (oBCP) is usually less aggressive, however applied adjuvant treatment is often less potent resulting in an impaired disease free survival and overall survival in this group. This study tries to answer the following questions for the biological subtypes of oBCP (70+ y):, Methods: Between 1992 and 2008 the BRENDA ('BRENDA' = quality of BREast caNcer care unDer evidence-bAsed guidelines) study group recorded medical data of 17 participating certified breast cancer centers in Germany. We performed a retrospective multi-center database analysis of 5632 patient records. Guideline-adherent-treatment (GL+) of oBCP(n = 1918) was compared to GL+ of yBCP(n = 3714)., Results: OBCP were more likely to have hormone receptor positive (HR+) and HER2neu negative (HER2-) breast cancer (77.5% vs 74.5%). The rate of GL- was significantly different (p < 0.001) between the age groups and the biological subgroups (yBCP vs oBCP: 21.8%vs38.8% (HR+/HER2-); 30.6%vs49.7% (HR+/HER2+); 23.6%vs69.5% (HR-/HER2+); 31.4%vs67.8% (TNBC)). The survival parameters for HR+/HER2- and TNBC were significantly worse in case of GL- regarding chemotherapy, and if applicable endocrine therapy. A similar association only existed in HR-/HER2+ tumors for GL- for radiotherapy and in HR+/HER2+ tumors for chemotherapy., Conclusions: Beside the significantly different distribution of biological subtypes in the age groups there is an association between biological subtype, and GL+ influencing survival parameters in oBCP., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

The progesterone receptor (PR) has been increasingly well described as an important mediator of the pathogenesis and progression of breast cancer. The aim of this study was to assess the role of PR status as a prognostic factor in addition to other well-established prognostic factors. Data from five independent German breast cancer centers were pooled. A total of 7,965 breast cancer patients were included for whom information about their PR status was known, as well as other patient and tumor characteristics commonly used as prognostic factors. Cox proportional hazards models were built to compare the predictive value of PR status in addition to age at diagnosis, tumor size, nodal status, grading, and estrogen receptor (ER) status. PR status significantly increased the accuracy of prognostic predictions with regard to overall survival, distant disease-free survival, and local recurrence-free survival. There were differences with regard to its prognostic value relative to subgroups such as nodal status, ER status, and grading. The prognostic value of PR status was greatest in patients with a positive nodal status, negative ER status, and low grading. The PR-status adds prognostic value in addition to ER status and should not be omitted from clinical routine testing. The significantly greater prognostic value in node-positive and high-grade tumors suggests a greater role in the progression of advanced and aggressive tumors.

Purpose: This study was aimed to investigate incidence, circumstances and consequences of acute compartment syndrome (CS) of the lower extremity after gynecological operations in lithotomy position by collecting data from departments of Obstetrics and Gynecology in Germany., Design: Retrospective observational study., Setting: Departments of Obstetrics and Gynecology in the area of North Rhine (Germany), Methods: A 24-item questionnaire was sent to 168 gynecological departments. In addition, cases anonymously reported to the Expert Committee for Medical Malpractice Claims of the Medical Association of North Rhine between 2002 and 2012 were analyzed., Main Outcome Measure: Incidence of acute CS after gynecological operations., Results: A total of 59 questionnaires (35 %) were returned for analysis, reporting 21 cases of CS. Based on the collected data, we calculated an incidence of postoperative CS ranging between 0.067 % and 0.28 %. All reported cases of postoperative CS occurred after surgeries in lithotomy position, 57.1 % of cases occurred after laparoscopic procedures and 76.2 % after procedures longer than 4 h. Overall, 61.0 % of departments do not routinely inform about the risk of this complication when they get patients' informed consent. Reported prevention strategies were inconsistent and ranged from none to multiple measures., Conclusion: CS is a complication clearly associated with long lasting gynecological operations in Lithotomy position. Despite a relatively high incidence, so far no guidelines on perioperative management and medicolegal aspects exist and preventive measures are heterogeneous among institutions. The need for guidelines and recommendations by an expert committee has been identified.

Background: Evidence is accumulating that circulating tumor cells (CTC) out of peripheral blood can serve as prognostic marker not only in metastatic but also in early breast cancer (BC). Various methods are available to detect CTC. Comparisons between the different techniques, however, are rare., Material and Methods: We evaluate two different methods for CTC enrichment and detection in primary BC patients: the FDA-approved CellSearch System (CSS; Veridex, Warren, USA) and a manual immunocytochemistry (MICC). The cut-off value for positivity was ≥1 CTC., Results: The two different nonoverlapping patient cohorts evaluated with one or the other method were well balanced regarding common clinical parameters. Before adjuvant CHT 21.1% (416 out of 1972) and 20.6% (247 out of 1198) of the patients were CTC-positive, while after CHT 22.5% (359 out of 1598) and 16.6% (177 out of 1066) of the patients were CTC-positive using CSS or MICC, respectively. CTC positivity rate before CHT was thus similar and not significantly different (P = 0.749), while CTC positivity rate immediately after CHT was significantly lower using MICC compared to CSS (P < 0.001)., Conclusion: Using CSS or MICC for CTC detection, we found comparable prevalence of CTC before but not after adjuvant CHT.

Circulating tumor cells (CTCs) are promising biomarkers for diagnosis and therapy in systemic cancer. However, their infrequent and unreliable detection, especially in nonmetastatic cancer, currently impedes the clinical use of CTCs. Because leukapheresis (LA) targets peripheral blood mononuclear cells, which have a similar density to CTCs, and usually involves processing the whole circulating blood, we tested whether LA could substantially increase CTC detection in operable cancer patients. Therefore, we screened LA products generated from up to 25 L of blood per patient in two independent studies, and found that CTCs can be detected in more than 90% of nonmetastatic breast cancer patients. Interestingly, complete white blood cell sampling enabled determining an upper level for total CTC numbers of about 100,000 cells (median, 7,500 CTCs) per patient and identified a correlation of CTC numbers with anatomic disease spread. We further show that diagnostic leukapheresis can be easily combined with the US Food and Drug Administration-approved CellSearch system for standardized enumeration of CTCs. Direct comparison with 7.5 mL of blood revealed a significantly higher CTC frequency in matched LA samples. Finally, genomic single-cell profiling disclosed highly aberrant CTCs as therapy-escaping variants in breast cancer. In conclusion, LA is a clinically safe method that enabled a reliable detection of CTCs at high frequency even in nonmetastatic cancer patients, and might facilitate the routine clinical use of CTCs as in the sense of a liquid biopsy. Combined with technologies for single-cell molecular genetics or cell biology, it may significantly improve prediction of therapy response and monitoring of early systemic cancer.

The German, Austrian and Swiss (D.A.CH) Societies of Senology gathered together in 2012 to address dwelling questions regarding axillary clearance in breast cancer patients. The Consensus Panel consisted of 14 members of these societies and included surgical oncologists, gynaecologists, pathologists and radiotherapists. With regard to omitting axillary lymph node dissection in sentinel lymph node macrometastases, the Panel consensually accepted this option for low-risk patients only. A simple majority voted against extending radiotherapy to the axilla after omitting axillary dissection in N1 disease. Consensus was yielded for the use of axillary ultrasound and prospective registers for such patients in the course of follow-up. The questions regarding neoadjuvant therapy and the timing of sentinel lymph node biopsy failed to yield consensus, yet both options (before or after) are possible in clinically node-negative disease., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

There is a growing body of evidence that HER2 status can change during disease recurrence or progression in breast cancer patients. In this context, re-evaluation of HER2 status by assessment of HER2 expression on circulating tumor cells (CTCs) is a strategy with potential clinical application. The aim of this trial was to determine the HER2 status of CTCs in metastatic breast cancer patients comparing two CTC assays. A total of 254 patients with metastatic breast cancer from nine German university breast cancer centers were enrolled in this prospective study. HER2 status of CTCs was assessed using both the FDA-approved CellSearch® assay and AdnaTest BreastCancer™. Using the CellSearch assay, 122 of 245 (50%) patients had ≥5 CTCs, and HER2-positive CTCs were observed in 50 (41%) of these patients. Ninety of 229 (39%) patients were CTC positive using AdnaTest BreastCancer, and HER2 positivity rate was 47% (42 of 90). The rate of breast cancer patients with HER2-negative primary tumors but HER2-positive CTCs was 32% (25 of 78) and 49% (28 of 57) using the CellSearch assay and AdnaTest BreastCancer, respectively. Considering only those patients who had CTCs on both tests (n = 62), concordant results regarding HER2 positivity were obtained in 50% of the patients (31/62) (P = 0.96, κ = -0.006). HER2-positive CTCs can be detected in a relevant number of patients with HER2 negative primary tumors. Therefore, it will be mandatory to correlate the assay-dependent HER2 status of CTCs to the clinical response on HER2-targeted therapies.

Purpose: To evaluate the prognostic significance of primary tumor location and to examine whether the effect of adjuvant radiotherapy on survival varies according to tumor location in women with axillary node-positive (ALN+) breast cancer (BC)., Patients and Methods: Data were abstracted from the SEER database for 24,410 women aged 25-95 years, diagnosed between 1988-1997 with nonmetastatic T1-T2, ALN+ BC. Subgroup analyses were performed using interactions within proportional hazards models. Event was defined as death from any cause. Prognostic variables were selected using Akaike Information Criteria. Joint significances of subgroups were evaluated with Wald test., Results: Median follow-up was 10 years. In joint models, statistically significant interactions were found between tumor location, nodal involvement, type of surgery, and radiotherapy. Factorial presentation of interactions showed consistent 13% proportional reduction of mortality in all subgroups, except in women with medial tumors with > or = 4 ALN+ treated with mastectomy. In this subgroup, use of radiotherapy was associated with a 16% proportional increase in mortality., Conclusion: Medial tumor location is a significant adverse prognostic factor that should be considered in treatment decision- making for women with ALN+ BC. Improved survival was observed with radiotherapy use in all subgroups, except in women with medial tumors with > or = 4 ALN+ treated with postmastectomy radiotherapy. These findings raise concern that the favorable effect of radiotherapy may be offset by excess toxicities in the latter subgroup.

Introduction: Due to technical improvements and growing experience, hysterectomies are performed laparoscopically more and more frequently. We analyzed 43 total laparoscopic hysterectomies (TLH) of the years 2005 and 2006 and compared them with 87 vaginal (VH) and 103 abdominal hysterectomies (AH)., Methods: Patients' original files and surgery reports of the TLHs, VHs and AHs were analyzed retrospectively for the indication of surgery, patients' age, weight, parity, time for surgery, uterus weight, blood loss, post-operative need of analgetics, hospital stay, complications and so on. Data were compared with Student's t test and chi(2) test., Results: Indications for TLH were fibroids (n = 21), endometrial cancer (n = 10), bleeding anomalies (n = 7), dysplasia of the cervix uteri (n = 3) and others. In 23/43 cases salpingo-ovarectomy was added, in six cases laparoscopic pelvic or paraaortic lymphadenectomy (LNE) was performed. Looking at cases without LNE, patients' median age was 46 years (32-72), median weight 68 kg (53-115), median time for TLH 130 min (75-270), median uterus weight 150 g (44-954), median blood loss 200 ml (50-600), post-operative analgetica were given for 1.5 days (0-12), and post-operative hospital stay was 6 days (2-15). Indications for VH were genital prolapse (n = 53, 61%), often combined with fixative procedures (n = 50). In this group, median age was significantly higher (median 56 years, P < 0.001). VH was the fastest (median 90 min, P < 0.001), but blood loss was highest (median 300 ml, P = 0.07). In cases with AH, uterus weight was significantly higher (median 290 g, P < 0.001), as well as the need for analgetics (median 4 days, P = 0.001), and the hospital stay was longest (median 8 days, P < 0.001). Major complications of TLH were bladder injury (3x), of VH rectum lesion (2x, both at pelvic repair measures), of AH post-operative ileus (2x) and vesico-vaginal fistula (1x)., Conclusion: For many patients TLH is a safe and less invasive alternative, especially towards AH, and shows significantly better post-operative reconstitution. Although VH is faster and shows comparable post-operative results, TLH offers the advantage to view the intra-abdominal situs and perform additional steps in case of pathologies.

Background: The aim of this study was to evaluate the current management of skin-sparing mastectomy in German hospitals and to determine its oncologic safety. For this purpose, 100 surgeons were surveyed regarding their use of skin-sparing mastectomy., Results: Almost all surveyed hospitals performed skin-sparing mastectomy. Most of them believe that the recurrence rate is equal to that of conventional mastectomy. 95% regard inflammatory cancer as a contraindication to skin-sparing surgery. Most of the hospitals thin out the skin without leaving any macroscopic glandular tissue behind, and 73% leave the nipple-areola complex (NAC) on the basis of frozen sections. Volume replacement is most commonly done with latissimus dorsi muscle flaps and pedicled TRAM flaps. In 76% of the surveyed hospitals, reconstruction after mastectomy is performed by the gynecological department., Conclusion: Skin-sparing mastectomy is considered to be the best cosmetic option for breast reconstruction in selected breast cancer patients. At present, statistical proof of its oncologic safety is lacking. The surgical techniques used for skin-sparing mastectomy have not yet been standardized. In order to achieve standardization, careful discussion-making and evaluation remain important.

The general practitioner called upon to provide medical care to the older woman for diseases other than gynecological or obstetric illness, should not neglect to recommend gynecological cancer screening, which is of particular importance in this group. In many differential diagnoses, the general practitioner must also give consideration to gynecological-obstetric aspects. Thus, for example, when a patient presents with lower abdominal pain, gynecological pathology must always be taken into account. Numerous preparations with differing actions and applications used in contraception or hormone therapy in the post-menopausal woman, require individual counseling by the gynecologist.

The term 'extreme' whole-body hyperthermia (WBH) describes the procedure of raising a patients' body-core temperature to 41.5-42.0 degrees C for 60 min. WBH represents the only hyperthermia technique that enables systemic heat treatment in patients with disseminated malignancies and is, therefore, usually combined with systemic chemotherapy. Up to now, several WBH-approaches have proved to be safe and associated with acceptable toxicity rates when radiant heat devices are employed. Until the late 1990s, the use of radiant WBH was restricted to a few specialized treatment centres worldwide. During the last 5 years, a larger number of WBH-devices were put into operation particularly in Germany. As a result, a novel generation on phase II trials on chemotherapy and adjunctive WBH in patients with various malignancies has been completed. Based on the promising results observed herein, first multi-centric phase III-trials on chemotherapy +/- WBH have been initiated, with a considerable number of patients treated at German institutions. The authors are members of the 'Interdisciplinary Working Group for Hyperthermia' ('Interdisziplinäre Arbeitsgruppe Hyperthermie'), a sub-group of the German Cancer Society. They formulated these guidelines in order to standardize the WBH treatment procedure and supportive measures, to provide some uniformity in the selection of patients to be treated and to define criteria of a successful WBH-treatment. These recommendations may be helpful to ensure the quality of WBH performed at different institutions.

Background: The extent of axillary lymph node involvement represents the foremost important prognostic parameter in primary breast cancer, and, thus, is one of the main determinants for subsequent systemic treatment. Nevertheless, the relevance of the initial axillary lymph node status on survival after disease recurrence is discussed controversially. Persisting prognostic impact after relapse would identify lymph node status as a marker for tumor biology, in contrast to a simply time-dependent phenomenon., Method: Retrospective analysis of 813 patients with locoregional or distant recurrence of primary breast cancer, who were primarily diagnosed with their disease at the I. Frauenklinik, Ludwig-Maximilians-University, Munich, and the University Hospital in Berlin-Charlottenburg, Germany, between 1963 and 2000. To be eligible, patients were required to have been treated for resectable breast cancer free of distant disease at the time of primary diagnosis, and must have undergone systematic axillary lymph node dissection. Patients with unknown tumor size or nodal status were excluded from the study. All data were gathered contemporaneously and compared with original patients files, as well as the local cancer registry, ensuring high quality of data. The median observation time was 60 (standard deviation 44) months., Results: At time of primary diagnosis, 273 patients (33.6%) were node-negative, while axillary lymph node metastases were detected in 540 patients (66.4%). In univariate analysis tumor size, axillary lymph node status, histopathological grading, hormone receptor status, as well as peritumoral lymphangiosis and haemangiosis carcinomatosa were significantly correlated with survival after relapse (all, P < 0.0001). Kaplan-Meier analysis estimated the median survival time after relapse in node-negative patients to be 42 months (31-52 months, 95% CI), and 20 months in patients with 1-3 axillary lymph node metastases (16-24 months, 95% CI), compared to 13 months in patients with at least 4 involved axillary nodes (12-15 months, 95% CI). Multivariate logistic regression analysis, allowing for tumor size, axillary lymph node status, histopathological grading, presence of lymphangiosis carcinomatosa, relapse site and disease-free interval confirmed all parameters, except of histopathological grading (P = 0.14), as significant, independent risk factors for cancer associated death. Subgroup analyses, accounting for site of relapse and duration of disease-free interval, confirmed primary lymph node status as independent predictor for cancer-associated death after relapse., Conclusion: Lymph node involvement at primary diagnosis of breast cancer patients predicts an unfavorable outcome after first recurrence, independently of the site of relapse and disease-free interval. These observations support the hypothesis that primary lymph node involvement is not a merely time-dependent indicator for tumor progression, but indicates tumors with aggressive biological behavior.

Background and Objective: Current meta-analyses have left in doubt whether general breast screening increases survival rate. This study investigated whether efforts at early diagnosis of cancer in the 1980s have had an effect on average tumor size at first diagnosis and on survival rate., Patients and Methods: From 1981 to 1990, 1656 consecutive patients (average age 56.6 years) at the I. Women's Clinic at the Ludwig-Maximilian University of Munich and the Women's Clinic Berlin-Charlottenburg were operated on for primary breast cancer. In a retrospective analysis, average tumor size at the primary operation and survival rate were determined for two periods: 1981-1985 (n=849) and 1986-1990. Mean follow-up time was 63 months., Results: There was no difference between the two cohorts regarding age (p = 0.77) and axillary node status (p = 0.14). During the follow-up period there was a gradual decrease in the tumor size at first diagnosis. (Pearson's correlation coefficient: -0.79, p < 0.001). Average tumor size in those operated on was 25 mm up to 1985, and 21 mm after 1986 (p < 0.001). Until 1985, the initial reason for mammography was the planned subsequent operation in 19% of patients (n = 164), and in 27% (n = 215; p < 0.001) since 1986. But there was no statistically significant rise in disease-specific survival rate (log rank, p=0.48). Multivariate analysis confirmed the conventional prognostic parameters, such as tumor size (relative risk 2.21) and axillary lymph node metastases (relative risk 3.57), but not the period of follow-up (p=0.90)., Conclusion: During the stated periods of follow-up there was a significant decrease in average tumor size at initial diagnosis. But this did not result in any demonstrably better disease-specific survival rate.

Background: Breast-conserving therapy has been demonstrated to be just as safe and a less disruptive experience compared with mastectomy for surgically manageable breast cancer. There is, however, no agreement in the literature about the impact of these procedures on several important aspects of quality of life (QOL). The purpose of the present study is to compare the long-term impact of these two surgical approaches on QOL in patients with identical tumor stages and to suggest possible shortcomings of the standard QOL questionnaires., Method: Between August 1999 and May 2000, QOL questionnaires were answered by 152 pair-matched patients at the I. Frauenklinik, Ludwig-Maximilians University Munich, as part of routine follow-up examinations. The pairs of patients, each consisting of one patient after mastectomy and one after breast conservation, were selected according to the highest degree of equivalence in tumor stage. All patients had been initially treated for stage I-III breast cancer without evidence of distant metastases. The QOL was evaluated by using the QLQ-C30 questionnaire version 2.0 of the EORTC Study Group on Quality of Life. We formulated seven additional questions about the patients' satisfaction with the primary surgical treatment modality as viewed from their current perspective. The QOL questionnaires were answered after a median interval of 46 months following primary treatment., Results: Tumor stage, prognostic factors, and adjuvant systemic treatment were well balanced between the two groups. No differences between the two groups were observed in terms of all QOL items measured by the QLQ-C30. Our additional questions, however, revealed that patients in the mastectomy group were less satisfied with the cosmetic result of their primary operation (P < .0001), were more likely to feel basic changes in their appearance (P < .0001), and were more likely to be emotionally stressed by these facts (P < .0001). From their perspective at the time of completing the questionnaires, 11 patients in the mastectomy group (15%) would decide differently about the surgical treatment modality, compared with only 3 patients (4%) in the breast conservation group (P = .025)., Conclusion: While the primary surgical treatment modality seems to have no long-term impact on general QOL, certain body-image-related problems may be caused by mastectomy. Standard measuring instruments for QOL may fail to detect differences in satisfaction and adaptation with the primary surgical treatment modality.

Purpose: There is an urgent need for markers that can predict the efficacy of adjuvant chemotherapy in patients with solid tumors. This study was designed to evaluate whether monitoring of micrometastases in bone marrow can predict the response to systemic chemotherapy in breast cancer., Patients and Methods: Bone marrow aspirates of 59 newly diagnosed breast cancer patients with either inflammatory (n = 23) or advanced (> four nodes involved) disease (n = 36) were examined immunocytochemically with the monoclonal anticytokeratin (CK) antibody A45-B/B3 (murine immunoglobulin G(1); Micromet, Munich, Germany) before and after chemotherapy with taxanes and anthracyclines., Results: Of 59 patients, 29 (49.2%) and 26 (44.1%) presented with CK-positive tumor cells in bone marrow before and after chemotherapy, respectively. After chemotherapy, less than half of the previously CK-positive patients (14 of 29 patients; 48.3%) had a CK-negative bone marrow finding, and 11 (36. 7%) of 30 previously CK-negative patients were CK-positive. At a median follow-up of 19 months (range, 6 to 39 months), Kaplan-Meier analysis of 55 assessable patients revealed a significantly reduced overall survival (P =.011; log-rank test) if CK-positive cells were detected after chemotherapy. In multivariate analysis, the presence of CK-positive tumor cells in bone marrow after chemotherapy was an independent predictor for reduced overall survival (relative risk = 5.0; P =.016)., Conclusion: The cytotoxic agents currently used for chemotherapy in high-risk breast cancer patients do not completely eliminate CK-positive tumor cells in bone marrow. The presence of these tumor cells after chemotherapy is associated with poor prognosis. Thus, bone marrow monitoring might help predict the response to systemic chemotherapy.