Search

Background With more effective therapies for patients with advanced breast cancer (aBC), therapy sequences are becoming increasingly important. However, some patients might drop out of the treatment sequence due to deterioration of their life status. Since little is known about attrition in the real-world setting, this study assessed attrition in the first three therapy lines using a real-world registry. Methods Patients with information available on the first three therapy lines were selected from the German PRAEGNANT registry (NCT02338167). Attrition was determined for each therapy line using competing risk analyses, with the start of the next therapy line or death as endpoints. Additionally, a simple attrition rate was calculated based on the proportion of patients who completed therapy but did not start the next therapy line. Results Competitive risk analyses were performed on 3988 1st line, 2651 2nd line and 1866 3rd line patients. The probabilities of not starting the next therapy line within 5 years after initiation of 1st, 2nd and 3rd line therapy were 30%, 24% and 24% respectively. Patients with HER2-positive disease had the highest risk for attrition, while patients with HRpos/HER2neg disease had the lowest risk. Attrition rates remained similar across molecular subgroups in the different therapy lines. Conclusion Attrition affects a large proportion of patients with aBC, which should be considered when planning novel therapy concepts that specifically address the sequencing of therapies. Taking attrition into account could help understand treatment effects resulting from sequential therapies and might help develop treatment strategies that specifically aim at maintaining quality of life., Competing Interests: Conflict of Interest E. B. has received honoraria from Novartis, Celgene, Eisai, Daiichi Sankyo, Merrimack, AstraZeneca, Riemser, Pfizer, Hexal, Amgen, and onkowissen.de for consulting, clinical research management, or medical education activities. J. E. has received honoraria/travel support from Roche, Celgene, Novartis, Pfizer, Lilly, Pierre Fabre, Teva, and Tesaro, AstraZeneca, Daiichi, Seagen, Gilead, StemLine, ClinSol. P. A. F. has received honoraria from Roche, Pfizer, Novartis, and Celgene; his institution conducts research for Novartis. A. D. H. has received honoraria from Roche, Novartis, Lilly, MSD, AstraZeneca, Seagen, GSK, ExactScience, Riemser, Teva, Onkowissen, Gilead, Menarini Stemline, Pfizer, Amgen, Pierre Fabre and Eisai and travel support from Roche, Novartis, Lilly, AstraZeneca, GSK, Exact Science, Gilead, Menarini Stemline and Pfizer. C. H. has received honoraria from Amgen, Celgene, Oncovis, Roche, and Pfizer. J. H. has received honoraria from Novartis, Roche, Celgene, Teva, and Pfizer, and travel support from Roche, Celgene, and Pfizer. C. K. has received honoraria from Amgen, Roche, Teva, Novartis, MSD, Axios, and Riemser. H.-C. K. has received honoraria from Pfizer, Novartis, Roche, Genomic Health/Exact Sciences, Amgen, AstraZeneca, Riemser, Carl Zeiss Meditec, TEVA, Theraclion, Janssen-Cilag, GSK, LIV Pharma, Lily, SurgVision, Onkowissen, Gilead, Daiichi Sankyo and MSD, travel support from Carl Zeiss Meditec, LIV Pharma, Novartis, Amgen, Pfizer, Daiichi Sankyo, Tesaro, Gilead and Menarini Stemline and owns stock of Theraclion SA. M. P. L. has received honoraria from Lilly, Pfizer, Roche, MSD, Hexal, Novartis, AstraZeneca, Eisai, Exact Sciences, Agendia, Daiichi-Sankyo, Grünenthal, Gilead, Pierre Fabre, PharmaMar, Samantree, Endomag, and medac for advisory boards, lectures, and travel support. V. M. Speaker honoraria: AstraZeneca, Daiichi-Sankyo, Eisai, Pfizer, MSD, Medac, Novartis, Roche, Seagen, Onkowissen, high5 Oncology, Medscape, Gilead, Pierre Fabre, iMED Institut. Consultancy honoraria: Roche, Pierre Fabre, PINK, ClinSol, Novartis, MSD, Daiichi-Sankyo, Eisai, Lilly, Seagen, Gilead, Stemline. Institutional research support: Novartis, Roche, Seagen, Genentech, AstraZeneca. Travel grants: AstraZeneca, Roche, Pfizer, Daiichi Sankyo, Gilead P. H. has received honoraria, unrestricted educational grants, and research funding from Amgen, Novartis, Hexal and Pfizer. A. S. has received honoraria from Roche, Celgene, AstraZeneca, Novartis, Pfizer, Zuckschwerdt Verlag GmbH, Georg Thieme Verlag, Aurikamed GmbH, MCI Deutschland GmbH, bsh medical communications GmbH, and promedicis GmbH. H. T. has received honoraria from Novartis, Roche, Celgene, Teva, and Pfizer, and travel support from Roche, Celgene, and Pfizer. M. W. received speaker honoraria from AstraZeneca, Celgene, Roche, MSD and Novartis. R. W. has received honoraria from Agendia, Amgen, APOGHEVA, Aristo, Astra Zeneca, Celgene, Clovis Oncology, Daiichi-Sankyo, Eisai, Esteve, Exact Sciences, ilead, Glaxo Smith Kline, Hexal, Lilly, Medstrom Medical, MSD, Mundipharma, Mylan, Nanostring, Novartis, Odonate, Paxman, Palleos, Pfizer, Pierre Fabre, PINK, PumaBiotechnolgogy, Riemser, Roche, Sandoz/Hexal, Sanofi Genzyme, Seattle Genetics /Seagen, Sidekick, Stemline, Tesaro Bio, Teva, Veracyte, Viatris, Wiley, FOMF, Aurikamed, Clinsol, Pomme Med, medconcept, MCI, MediSeminar. F. A. T. has received speaker and consultancy honoraria from AstraZeneca, Gilead, GSK, MSD, Novartis, Onkowissen, Pfizer, Roche. C. B. W. has received honoraria from Teva, AstraZeneca, Novartis, Pfizer, and Roche D. L. has received honoraria from Amgen, Loreal, Pfizer, Novartis, Eli Lilly, Samsung, Celgene, Astra Zeneca, Teva and GSK H. H. received speaker honorar for: Novartis Pharma GmbH and LEO Pharma GmbH and Grant/Research support from: Novartis Pharma GmbH. M. U. has received honoraria for advisory boards and travel support, payed to the employer from Abbvie, Amgen, AstraZeneca, BMS, Celgene, Daiichi Sankyo, Eisai, Lilly Deutschland, Lilly Int., MSD, Mundipharma, Myriad Genetics, Odonate, Pfizer, Puma Biotechnology, Roche, Sanofi Aventis Deutschland, Teva Pharmaceuticals Ind Ltd, Novartis, Pierre Fabre, Clovis Oncology, and Seattle Genetics W. J. has received honoraria and research grants from Sanofi-Aventis, Novartis, Lilly, Pfizer, Roche, Chugai, AstraZeneca, MSD, and Daiichi Sankyo L. L. M. received honoraria from Amgen, AstraZeneca, Celgene, Gilead, Lilly, MSD, Novartis, Pfizer, Roche and Eisai for advisory boards, lectures and travel support. S. Y. B. has received honoraria from Roche, Novartis, Pfizer, MSD, Teva, and AstraZeneca T. N. F. has received honoraria from Novartis, Roche, Pfizer, Teva, Daiichi Sankyo, AstraZeneca, and MSD All remaining authors have declared that they have no conflicts of interest = M. W. B., S. U., C. G., T. L., C. M., D. W., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commecial purposes, or adapted, remixed, transformed or built upon. ( https://creativecommons.org/licenses/by-nc-nd/4.0/ ).)

Introduction: Adjuvant treatment of patients with early-stage breast cancer (BC) should include an aromatase inhibitor (AI). Especially patients with a high recurrence risk might benefit from an upfront therapy with an AI for a minimum of five years. Nevertheless, not much is known about the patient selection for this population in clinical practice. Therefore, this study analyzed the prognosis and patient characteristics of postmenopausal patients selected for a five-year upfront letrozole therapy., Patients and Methods: From 2009 to 2011, 3529 patients were enrolled into the adjuvant phase IV PreFace clinical trial (NCT01908556). Postmenopausal hormone receptor-positive BC patients, for whom an upfront five-year therapy with letrozole (2.5 mg/day) was indicated, were eligible. Disease-free survival (DFS), overall survival (OS) and safety in relation to patient and tumor characteristics were assessed., Results: 3297 patients started letrozole therapy. The majority of patients (n = 1639, 57%) completed the five-year treatment. 34.5% of patients continued with endocrine therapy after the mandated five-year endocrine treatment. Five-year DFS rates were 89% (95% CI: 88-90%) and five-year OS rates were 95% (95% CI: 94-96%). In subgroup analyses, DFS rates were 83%, 84% and 78% for patients with node-positive disease, G3 tumor grading, and pT3 tumors respectively. The main adverse events (any grade) were pain and hot flushes (66.8% and 18.3% of patients)., Conclusions: The risk profile of postmenopausal BC patients selected for a five-year upfront letrozole therapy showed a moderate recurrence and death risk. However, in subgroups with unfavorable risk factors, prognosis warrants an improvement, which might be achieved with novel targeted therapies., Competing Interests: Conflict of Interest P. G. received honoraria from Novartis, MSD, and AstraZeneca. K. A. received speaker honoraria from Roche Pharma AG, Pfizer Pharma GmbH and AstraZeneca. C. C. H. received honoraria from Roche, Pfizer, Novartis, AstraZeneca, Gilead, Daiichi Sankyo, Eisai, Gilead and MSD, and received travel grants from Daiichi Sankyo. B. A. received honoraria from AstraZeneca, Gilead, Genomic Health, Roche, Novartis, Celgene, Lilly, MSD, Eisai, Stemline, Teva, Tesaro, Daiichi Sankyo and Pfizer. Received travel grants from AstraZeneca, Roche, Novartis, Celgene, Lilly, Eisai, Stemline, Daiichi Sankyo and Pfizer. Participated in the data safety monitoring board or advisory boards for AstraZeneca, Gilead, Genomic Health, Roche, Novartis, Celgene, Lilly, MSD, Eisai, Tesaro, Daiichi Sankyo and Pfizer. S. K. received honoraria from Amgen, Celgene, Daiichi Sankyo, Novartis and Roche. C. T. received honoraria for advisory boards and lectures from Amgen, AstraZeneca, Celgene, Daiichi Sankyo, Eisai, Gilead, Lilly, MSD, Mylan, Nanostring, Novartis, Pfizer, Pierre Fabre, Puma, Roche, Seagen, Vifor. H.-C. K. has received honoraria from Pfizer, Novartis, Roche, Genomic Health/Exact Sciences, Amgen, AstraZeneca, Riemser, Carl Zeiss Meditec, Teva, Theraclion, Janssen-Cilag, GSK, LIV Pharma, Lilly, Daiichi Sankyo, Gilead, Zuellig, travel support from Carl Zeiss Meditec, LIV Pharma, Novartis, Amgen, Pfizer, Daiichi Sankyo, Tesaro, Gilead, AstraZeneca, Zuellig, Stemline, participated in data safety monitoring board or advisory boards for Pfizer, Novartis, SurgVision, Carl Zeiss Meditec, Amgen, Onkowissen, MSD, Gilead, Daiichi Sankyo, Seagen, Genomic Health/Exact Sciences, Agendia, Lilly and owns stock of Theraclion SA. W. J. has received research grants and/or honoraria from Sanofi-Aventis, Daiichi Sankyo, Novartis, Roche, Pfizer, Lilly, AstraZeneca, Chugai, GSK, Eisai, Cellgene and Johnson & Johnson. A. S. reported grants from Celgene, Roche and AbbVie. Personal fees from Cellgene, Roche, Pfizer, AstraZeneca, Novartis, MSD, Tesaro, Lilly, Seagen, Gilead, GSK, Bayer, Amgen, and Pierre Fabre, and travel grants from Celgene, Roche, Pfizer and AstraZeneca. F. M. received honoraria from Amgen, AstraZeneca, Celgene, Clovis Oncology, CureVac, Eisai, Genomic Health, GlaxoSmithKline, Immunomedics, Janssen-Cilag, Lilly, MSD, Novartis, Pfizer, PharmaMar, Roche, Seattle Genetics, Tesaro. M. W. S. received honoraria from AstraZeneca, Pfizer, Clovis, Mylan, Roche, Gedeon Richter, Carl Zeiss Meditec, travel support from Pfizer, Carl Zeiss Meditec. C. J. reports personal fees from AstraZeneca, Exact Sciences, Lilly, Novartis and Roche. V. M. received speaker honoraria from Amgen, AstraZeneca, Daiichi Sankyo, Eisai, GSK, Pfizer, MSD, Medac, Novartis, Roche, Teva, Seagen, Onkowissen, high5 Oncology, Medscape, Gilead. Consultancy honoraria from Hexal, Roche, Pierre Fabre, Amgen, ClinSol, Novartis, MSD, Daiichi Sankyo, Eisai, Lilly, Sanofi, Seagen, Gilead. Institutional research support from Novartis, Roche, Seagen, Genentech. Travel grants: Roche, Pfizer, Daiichi Sankyo. E. B. received honoraria from Novartis, Hexal, BMS, Lilly, Pfizer, Roche, MSD, Bayer, Ipsen, Bluebird, Braun and onkowissen.de for consulting, clinical research management or medical education activities. S. Y. B. has received honoraria from Roche Pharma, Novartis, Pfizer, MSD, Teva, AstraZeneca. T. N. F. has received honoraria from Novartis, Roche, Pfizer, Teva, Daiichi Sankyo, AstraZeneca and MSD. P. A. F. reports personal fees from Novartis, grants from Biontech, personal fees from Pfizer, personal fees from Daiichi Sankyo, personal fees from AstraZeneca, personal fees from Eisai, personal fees from MSD, grants from Cepheid, personal fees from Lilly, personal fees from Pierre Fabre, personal fees from SeaGen, personal fees from Roche, personal fees from Hexal, personal fees from Agendia, personal fees from Gilead. C.R. received honoraria from MSD and AstraZeneca, travel expenses from the Swiss Society of Senology and the Swiss Society of Gynecology. All of the remaining authors declare that they do not have any conflicts of interest., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial-License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).)

Background Comprehensive data from prospective clinical trials have led to a high level of evidence establishing CDK4/6 inhibitors in combination with endocrine treatment (CDK4/6i + ET) as a standard for the treatment of HER2-negative, hormone receptor-positive (HER2- HR+) breast cancer patients in the first-line advanced therapy setting. Data on patient populations that have been treated in the real-world setting may provide an insight into changes of patient characteristics and prognosis over time. Methods The data were extracted from the prospective real-world registry PRAEGNANT (NCT02338167). Patients had to have HER2- HR+ advanced breast cancer in the first-line metastatic setting. The chosen therapies were described as well as progression-free survival (PFS) and overall survival (OS) in relation to the given therapies and time periods during which they were indicated. Results CDK4/6 inhibitors have been rapidly implemented since their introduction in November 2016. In recent years (2018 - 2022), about 70 - 80% of the patient population have been treated with CDK4/6 inhibitors, while endocrine monotherapy was given to about 10% and chemotherapy to about 15% of all patients. The prognosis was worst in patients treated with chemotherapy. Recently, mainly patients with a good prognosis are being treated with endocrine monotherapy, and patients who are treated with chemotherapy have an unfavorable prognosis. The PFS and OS of patients treated with CDK4/6i + ET have remained similar over time despite changes in patient characteristics. Conclusion A treatment with CDK4/6i + ET has rapidly become the therapy standard for patients in the first-line advanced breast cancer setting. After the implementation of CDK4/6i + ET, endocrine monotherapy is only given to patients with a very favorable prognosis, while chemotherapy is provided to patients with a rather unfavorable prognosis. These changes in patient characteristics did not seem to influence the prognosis of patients treated with CDK4/6i + ET., Competing Interests: Conflict of Interest T. E. received honoraria from AstraZeneca, Eli Lilly, Daiichi Sankyo, Gilead, GSK, Novartis, Pfizer, Roche. P. A. F. has 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. D. L. has received honoraria from Amgen, Novartis, Pfizer, Eli Lilly, Teva, Loreal, GSK, MSD, Roche, onkowissen, High5MD and AstraZeneca. A. D. H. has received honoraria from Teva, GenomicHealth, Lilly, AstraZeneca, Novartis, Pfizer, Pierre Fabre, SeaGen, and Roche. V. M. has received speaker honoraria from Amgen, AstraZeneca, Daiichi Sankyo, Eisai, Pfizer, MSD, Novartis, Roche, Teva, and Seattle Genetics and consultancy honoraria from Genomic Health, Hexal, Roche, Pierre Fabre, Amgen, ClinSol, Novartis, MSD, Daiichi Sankyo, Eisai, Lilly, Tesaro, and Nektar. H.-C. K. has received honoraria from Carl Zeiss Meditec, Theraclion, Novartis, Amgen, AstraZeneca, Pfizer, GSK, SurgVision, Onkowissen, Agendia, Gilead, Lilly, Daiichi Sankyo and Genomic Health/Exact Sciences and travel support from Tesaro and Daiichi Sankyo; he owns stocks of Theraclion and Phaon scientific. H. T. has received honoraria from Novartis, Roche, Celgene, Teva, and Pfizer and travel support from Roche, Celgene, and Pfizer. J. E. has received consulting fees from AstraZeneca, Daiichi Sankyo, Pfizer, Novartis, Lilly, Pierre Fabre, Roche, and Tesaro; contracted research from Daiichi Sankyo, Pfizer, Lilly, Novartis, Seattle Genetics, AstraZeneca, Roche, and Odonate; and travel support from Astra Zeneca, Daiichi Sankyo, Celgene, Pfizer, Novartis, Lilly, and Tesaro. M. Wa. received grants from AstraZeneca, Celgene, Roche, MSD, and Novartis during the conduct of the study. E. B. has received honoraria from Novartis, Pfizer, Amgen, Daiichi Sankyo, and onkowissen.de. P. W. has received honoraria for scientific talks and grants from Amgen, AstraZeneca, Roche, Daiichi Sankyo, Gilead, Lilly, Celgene, GSK, Novartis, MSD, Pfizer, Teva, Eisai, Clovis, and Tesaro. C. H. has received honoraria from Roche, Pfizer, AstraZeneca, Novartis, and Onkovis. C. M. K. has received honoraria from Amgen, AstraZeneca, Eli Lilly, MSD, Novartis, Pfizer, Onkotrakt, PharmaMar, Riemser, Roche, Tesaro, Hilotherm, and NewCo; research grants from AstraZeneca, BMS, Immunomedics, MSD, NewCo, Novartis, Pfizer, PharmaMar, Reimser, Roche, and Seattle Genetics; and travel support from Amgen, AstraZeneca, Hexal, Immunomedics, PharmaMar, Pfizer, Tesaro, and Teva Oncology. R. W. has received honoraria from Amgen, AstraZeneca, Celgene, Daiichi Sankyo, Esai, Exact Science, Nanostring, GSK, Hexal, Lilly, MSD, Mundipharma, Novartis, Odonate, Pfizer, Pierre Fabre, Riemser, Roche, Sandoz, Seattle Genetics, Tesaro Bio, Teva, and Viatris. M. U. has received honoraria from Abbvie, Amgen, AstraZeneca, BMS, Celgene, Daiichi Sankyo, Eisai, Lilly Deutschland, Lilly Int., MSD, Mundipharma, Myriad Genetics, Odonate, Pfizer, Puma Biotechnology, Roche, Sanofi Aventis Deutschland, Teva Pharmaceuticals Ind Ltd, Novartis, Pierre Fabre, Clovis Oncology, and Seattle Genetics. L. L. M. received honoraria from Amgen, AstraZeneca, Celgene, Gilead, Lilly, MSD, Novartis, Pfizer, Roche and Eisai for advisory boards, lectures and travel support. W. J. has received honoraria and research grants from Sanofi-Aventis, Novartis, Lilly, Pfizer, Roche, Chugai, AstraZeneca, MSD, and Daiichi Sankyo. F. A. T. has received honoraria from GSK, Hexal, MSD, Novartis, Pfizer, Roche and Tesaro and travel expenses from GSK. M. We. has participated on advisory boards for AstraZeneca, Lilly, MSD, Novartis, Pfizer and Roche. M. P. L. has received honoraria from Lilly, Pfizer, Roche, MSD, Novartis, AstraZeneca, Eisai, Exact Sciences, Pierre-Fabre, PharmaMar, Gilead, Daiichi Sankyo, Grünenthal, Samantree, Sysmex, pfm and medac for advisory boards, lectures, and travel support. S. Y. B. has received honoraria from Roche, Novartis, Pfizer, MSD, Teva, and AstraZeneca. T. N. F. has received honoraria from Novartis, Roche, Pfizer, Teva, Daiichi Sankyo, AstraZeneca, and MSD. A. S. received research grants from Celgene, Roche, honoraria from Amgen, AstraZeneca, Aurikamed, Bayer, Celgene, Clinsol, Connectmedica, Gilead, GSK, I-MED, Lilly, MCI Deutschland, Metaplan, MSD, Nanostring, Novartis, Onkowissen.de, Promedicis, Pfizer, Pierre Fabre, Roche, Seagen, Streamedup, Teva, Tesaro, Thieme and travel support from Celgene, Pfizer, Roche. All others (A. H., P. H., P. K., H.-M. E., M. M., D. H., L. H., M. W.B, S. U., D. W.) have declared that they do not have any conflicts of interest., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commecial purposes, or adapted, remixed, transformed or built upon. ( https://creativecommons.org/licenses/by-nc-nd/4.0/ ).)

Purpose Pertuzumab and T-DM1 are two efficient anti-HER2 treatments for patients with HER2-positive advanced breast cancer. While pertuzumab is usually given in first-line treatment and T-DM1 in second-line treatment, standard therapy options seem to be exhausted up to now after the treatment of patients with these two therapy options. Therefore, it is important to have data that describes the therapy situation and prognosis after T-DM1 treatment. Methods The PRAEGNANT metastatic breast cancer registry (NCT02338167) is a prospective registry for breast cancer patients with a focus on molecular biomarkers. Patients of all therapy lines with any kind of treatment are eligible. Collected data comprises therapies, adverse events, quality of life and other patient reported outcomes. Here we report on the patient characteristics and descriptive prognostic data for HER2-positive patients who have completed a treatment with T-DM1. Therapy patterns after T-DM1 and progression-free survival are reported as well as overall survival. Results A total of 85 patients were identified for the study who were prospectively observed during therapy after the termination of T-DM1. The main reason for T-DM1 termination was progress. Following T-DM1, lapatinib, trastuzumab and chemotherapy were the main therapy choices. Median progression-free survival was 4.8 months (95% CI: 3.2 - 6.3) and median overall survival was 18.4 months (95% CI: 15.5 - 21.3). Conclusions Therapy options after T-DM1 in a real-world setting seem to exhibit a relevant clinical efficacy, supporting the concept of continuous anti-HER2 treatments in the advanced therapy setting for breast cancer patients. Novel therapies are needed to improve the rather short median progression-free survival., Competing Interests: Conflict of Interest J. E. received honoraria from Pfizer and Eisai for lectures and travel support and from Novartis for advisory boards. W. J. received research grants and/or honoraria from Sanofi-Aventis, Daiichi Sankyo, Novartis, Roche, Pfizer, Lilly, AstraZeneca, Chugai, GSK, Eisai, Cellgene, Johnson& Johnson. F. O. received speaker and consultancy honoraria from Amgen, Celgene, AstraZeneca, Novartis, Roche, Pierre Fabre, Pfizer, Teva and MSD. H.-C. K. received honoraria from Carl Zeiss meditec, Teva, Theraclion, Novartis, Amgen, AstraZeneca, Pfizer, Janssen-Cilag, GSK, LIV Pharma, Roche, Daiichi Sankyo and Genomic Health and owns stock of Theraclion and Phaon scientific. P. H. received honoraria, unrestricted educational grants and research funding from Amgen, AstraZeneca, Eli Lilly, MSD, Novartis, Pfizer and Roche. H. T. received honoraria from Novartis, Roche, Celgene, Teva and Pfizer and travel support from Roche, Celgene and Pfizer. J. E. received honoraria from Roche, Celgene, Novartis, Pfizer, Pierre Fabre and Teva and travel support from Celgene, Pfizer, Teva and Pierre Fabre. D. L. received honoraria from Amgen, AstraZeneca, Celgene, Eli Lilly, GSK, Loreal, MSD, Novartis, onkowissen.de, Pfizer, Sanofi, Teva. M. W. received speaker honoraria from Astra Zeneca, Celgene and Novartis. V. M. received speaker honoraria from Amgen, AstraZeneca, Celgene, Daiichi Sankyo, Eisai, Pfizer, Pierre-Fabre, Novartis, Roche, Teva and Janssen-Cilag and consultancy honoraria from Genomic Health, Roche, Pierre Fabre, Amgen, Daiichi Sankyo and Eisai. M. W. B.’s institution received research funding from Novartis and Biontech. E. B. received honoraria from Novartis, Hexal and onkowissen.de for consulting, clinical research management or medical education activities. P. W. received honoraria from Amgen, AstraZeneca, MSD, Novartis, Pfizer, Lilly, Roche, Teva, Eisai, Clovis and Tesaro and consultancy honoraria from Amgen, AstraZeneca, MSD, Novartis, Pfizer, Roche, Clovis and Tesaro and research funding from Amgen, Novartis and Roche. C. H. received honoraria from Amgen, Celgene, Oncovis, Roche and Pfizer. C. K. received honoraria from Amgen, Roche, Teva, Novartis, MSD, Axios and Riemser. R. W. received honoraria from Roche, Celgene, Novartis, Pfizer, Teva, MSD, Eisai, Genomic Health, Agendia, Prosigna, Amgen, Pierre Fabre and AstraZeneca. C. T. received honoraria from Amgen, AstraZeneca, Celgene, Novartis, Pfizer and Roche. M. U. received honoraria from Abbvie, Amgen, AstraZeneca, Celgene, Daiichi Sankyo, Eisai, Lilly, MSD Merck, Mundipharma, Myriad Genetics, Pfizer, PUMA Biotechnology, Roche Sanofi Aventis, Novartis, Pierre Fabre – all honoraria to the institution/employer. P. A. F. received honoraria from Roche, Pfizer, Novartis and Celgene. His institution conducts research for Novartis. T. N. F. has participated on advisory boards for Amgen, Daiichi Sankyo, Novartis, Pfizer, and Roche and has received honoraria for lectures from Amgen, Celgene, Daiichi Sankyo, Roche, Novartis and Pfizer. A. S. received honoraria from Roche, Celgene, AstraZeneca, Novartis, Pfizer, Zuckschwerdt Verlag GmbH, Georg Thieme Verlag, Aurikamed GmbH, MCI Deutschland GmbH, bsh medical communications GmbH and promedicis GmbH. A. D. H. received honoraria from Genomic Health, Celgene, AstraZeneca, Lilly, GSK, Clovis, MSD, Novartis, Pfizer and Roche. All remaining authors have declared no conflicts of interest., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commecial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).)

Introduction Scarring and volume reduction of the axillary space resulting in persistent lymphedema is a side effect of axillary treatment in breast cancer patients. The aim of this paper is to describe the reduction of lymphedema achieved with a turnover flap. Materials and Methods Between October 2016 and May 2018, five patients with grade 2 lymphedema following breast cancer therapy underwent reconstructive surgery with a turnover flap. Complete excision of the symptomatic axillary scar tissue followed by re-augmentation using a turnover flap was performed. Subsequently, all patients underwent breast reconstruction using a distant flap reconnected to the thoracodorsal vessels. The circumference of both arms, quality of life and pain were measured before and after surgery. Results An average reduction in pain in the ipsilateral arm from 6 to 1 on the numerical scale as well as an improvement in quality of life (2.8 vs. 7.0) was observed. A decrease in lymphedema especially in the upper arm was identified. No complications such as secondary bleeding, infections or flap loss were observed. Conclusion Complete removal of the axillary scar tissue after breast cancer treatment and re-augmentation of the axilla with a turnover flap results in a reduction in ipsilateral lymphedema and an improvement in pain and quality of life. We interpret these findings as a result of the physiological re-alignment of the lymphatic vessels combined with a lymph node-containing local transposition flap. Therefore, re-augmentation with a turnover flap could be an effective non-microsurgical alternative to lymph node transplantation., Competing Interests: Conflict of Interest The authors declare that they have no conflict of interest.

Introduction This study investigates whether the time of diagnosis of foetal trisomy 21/18/13 and the frequency of termination of pregnancy have changed in the past 10 years. Material and Methods Retrospective study at the Tübingen University Centre for Women's Health in which the cases with ante- and postnatal diagnosis of trisomy were investigated. A prerequisite was that the patients be examined in the antenatal medicine department. The time of diagnosis, the frequency of termination of pregnancy and the gestational age in the case of a termination were assessed. Results Between 2007 and 2017, trisomy 21/18/13 was diagnosed in 498 foetuses and newborns. In 311 of the foetuses or newborns, trisomy 21 was identified; in 134, trisomy 18; and in 53, trisomy 13. The median gestational age at diagnosis in the case of foetuses with trisomy 21 was between 14.4 and 13.6 weeks of pregnancy. The rate of pregnancy terminations increased slightly from 66.7% between 2007 and 2010 to 75.5% between 2015 and 2017. The median gestational age at the time of termination remained constant at 14.9 and 15.0 weeks of pregnancy respectively. The median gestational age at diagnosis in the case of foetuses with trisomy 18/13 was between 13.6 and 14.6 weeks of pregnancy during the examination period. The percentages of affected pregnancies which were terminated in the three time periods increased slightly from 57.4 to 69.0%. The gestational age remained unchanged in this case at 15.0 and 15.1 weeks of pregnancy respectively. Conclusion The time of intrauterine diagnosis of trisomy 21/18/13 has not changed in the past 10 years. The frequency of termination of a pregnancy increased slightly and the time of termination remained unchanged.

The treatment of metastatic breast cancer has become more complicated due to increasing numbers of new therapies which need to be tested. Therapies are now being developed to treat special clinical or molecular subgroups. Even though intrinsic molecular subtypes play a major role, more and more new therapies for subgroups and histological subtypes are being developed, such as the use of PARP inhibitors to treat patients with BRCA mutations (breast and ovarian cancer). Supportive therapies are also evolving, allowing problems such as alopecia or nausea and vomiting to be treated more effectively. Treatment-related side effects have a direct impact on the prognosis of patients with metastatic breast cancer, and supportive therapy can improve compliance. Digital tools could be useful to establish better patient management systems. This overview provides an insight into recent trials and how the findings could affect routine treatment. Current aspects of breast cancer prevention are also presented.

This summary provides an overview of how new therapies or new aspects of established therapies relate to the latest findings. Neoadjuvant therapy, local therapy, new aspects of systemic therapy, and prognostic and predictive factors are presented. In the neoadjuvant setting, the association between pathological complete response (pCR) and prognosis is still of interest as is the identification of new molecular predictors for new therapies such as CDK4/6 inhibitors. As regards surgical treatment, the target is still to reduce the aggressiveness of surgery. To achieve this, a better understanding particularly of ductal carcinoma in situ is required. With regard to systemic therapy, more data on the best combinations and therapy sequences for existing therapies is available. Finally, the use of prognostic and predictive factors may help to avoid overtreatment and ensure that patients only receive therapies which have been shown to be effective for their specific condition and have fewer side effects.

In recent years, numerous new therapy options for patients with breast cancer have been developed in clinical studies, with some options already approved for routine treatment. As the speed at which innovations are introduced increases, the importance of conferences also increases, as conferences are where the data underpinning new therapies are usually presented for the first time. This review looks at publications of the ASCO (American Society of Clinical Oncology) and ESMO (European Society of Medical Oncology) conferences in 2017, summarizes them and evaluates them in the context of existing data. The focus is on new insights for neoadjuvant therapy and new treatment options in the metastatic setting, such as the use of CDK4/6 inhibitors or PARP inhibitors. The first results of treatments with checkpoint inhibitors are presented. With the patent expiry of trastuzumab, a number of study results for trastuzumab biosimilars have also been published. The digitization of patient care provides the first results on quality of life and prognosis of patients with advanced cancer. Digital communications between patients and physicians are being evaluated in several studies in Germany. As the discussion about patient-relevant endpoints for patients in the metastatic setting continues, overall survival rates from studies of big endocrine-based therapies are urgently needed. Preliminary analyses of small study cohorts offer initial insights. In the context of improving patient care, in the coming years, questions will center on which patients particularly benefit from certain therapies and which patients need particular protection from specific side effects. Questions about these predictors are raised in many scientific projects as attention increasingly focuses on this topic.

Purpose: Patient-reported outcomes (PROs) have been incorporated into clinical trials for many symptoms and medical conditions. A transition from paper-based capture of PROs to electronic PROs (ePROs) has recently started. This study reports on the feasibility of ePRO assessment in a prospective registry including molecular data for patients with advanced breast cancer., Methods: As part of the PRAEGNANT network, patients were invited by clinical trial staff, physicians, and nurses to complete three standardized Internet-based questionnaires (EQ 5D 5 L, CES-D and IPAQ). Feasibility was assessed by the staff members who assigned the user accounts by the patients. The completeness of the questionnaires was also assessed., Results: Fifteen of 17 patients who were asked agreed to participate to complete the PRO questionnaires (EQ-5D-5L and CES-D). However, the IPAQ (physical activity) questionnaire was only validly completed by 9 patients. Feasibility was ranked better by the physicians and dedicated clinical trial staff than by the nursing staff., Conclusions: Incorporating ePRO questionnaires into an advanced breast cancer registry is feasible, and no major hurdles were reported. Involving stakeholders from the start, the application is tailored to the capacities and abilities of both patients and clinical staff. The patients' compliance was better with some questionnaires, but others may present difficulties.

Question: Endoscopy is an integral part of surgical gynaecology and is playing an increasingly important role in ensuring adequate gynaecological training in the context of specialty training in general. At present, little is known about the expectations and notions of young junior doctors with respect to endoscopic training. For this reason, junior doctors throughout Germany were surveyed on this topic and asked to share their opinions. Methods: Using an anonymized standardized survey, the following information was elicited: importance of endoscopic training, willingness to take courses, expectations for instructors and the hospital, ideas about the number of required operations, both as a surgical assistant and as a surgeon, as well as satisfaction with the current status of training. The questionnaires were sent via the Young Forum (Junges Forum) of the German Society of Gynaecology and Obstetrics (DGGG) and the newsletter of the Working Group for Gynaecological Endoscopy (AGE). Results: The evaluation of the study was based on 109 completed questionnaires. The resident junior doctors were 31 years old on average and were in their third to fourth year of their specialty training on average. The majority of the participants (87 %) considered the learning of endoscopic techniques to be very important and advocated regular participation in endoscopy training courses. Among the participants, 48 % were prepared to invest up to €1500 of their own funds to attend courses up to twice a year during the entire specialty training period. The expectations of the instructors and institutions focused on technical expertise, the willingness and time for teaching and on the number and range of surgical procedures, followed by being granted leave for the courses and having costs covered for the courses. Thirty-eight per cent stated that their expectations had been completely or mostly met and 62 % said they had been met in part or inadequately. Eighty-three per cent of the respondents reported that they would change specialty training institutions in order to achieve their own goals in the context of specialty training. Conclusions: This study presents data for the first time on the satisfaction of young junior doctors and their expectations for endoscopic specialty training. The residents exhibited a high level of interest in endoscopy and a high level of willingness to actively shape the specialty training, including course participation. However, there appears to be a great deal of room for improvement for endoscopic specialty training, independent of the current training institution, training year or sex of the junior doctors.

Due to the declining mortality rates, malignant diseases have gained a chronic character for many gynaeco-oncology patients. The patients can expect to participate in social life and to an increasing extent in professional life for longer lengths of time. Promotion of rehabilitation and participation is an issue of the German 9th Social Security Code that explicitly places a focus on women. This is mainly of relevance for tumour patients with regard to assessment of the degree of severe disability, to compensate for disease-induced impairments and the possibilities for improving the participation of the afflicted subjects, especially by means of protective rights in professional life. Indeed, tumour patients do sometimes find themselves confronted with conflicting priorities between the entitlements guaranteed by social legislation and the compensation conferred by the health-care services, which can then be avoided when the facts are sufficiently known. For this purpose, the physician must be fully aware of the legal situation. The present article provides an overview of the procedures and reference points for appraisals. Patients need partners among their responsible physicians to help in the assertion of their claims. From the physician's side it is necessary to classify the reported complaints within the ever increasing knowledge about the direct side effects and the long-term side effects of cancer therapies. Against the background of an often life-long mental stress and the uncertain risk of recurrence, it should also be considered whether the concept of healing probation is in support of the targets of long-term disease management and social reintegration, also in the interest of society in general.

Introduction: Detection of sentinel lymph nodes (SLN) is the standard procedure to evaluate axillary lymph node status in breast cancer. In addition to known and established procedures such as the blue dye method and scintigraphy, this study investigated the efficacy of a method based on use of the fluorescent dye indocyanine green (ICG). Patients and Method: A total of 126 women with breast cancer histologically verified by punch biopsy were studied during surgical removal of SLN. In addition to SLN marking with technetium and scintigraphy, intra-individual comparison was done using indocyanine green (ICG) for marking instead of the standard blue dye. Results: Scintigraphy had a detection rate of 96 %; the detection rate with ICG was just under 89 %. A body mass index (BMI) > 40 was found to be a limiting factor for the fluorescent method. Investigation into potential toxicities associated with the use of the fluorescent dye ICG revealed no systemic or even local side effects. The fluorescent method was found to be significantly less expensive than the scintigraphy method. Conclusion: The ICG fluorescence technique for the detection of SLN was found to be a valid and feasible method in clinical practice when compared directly with the blue dye method and scintigraphy.

The appropriate surgical technique to treat patients with uterine fibroids is still a matter of debate as is the potential risk of incorrect treatment if histological examination detects a uterine sarcoma instead of uterine fibroids. The published epidemiology for uterine sarcoma is set against the incidence of accidental findings during surgery for uterine fibroids. International comments on this topic are discussed and are incorporated into the assessment by the German Society for Gynecology and Obstetrics (DGGG). The ICD-O-3 version of 2003 was used for the anatomical and topographical coding of uterine sarcomas, and the "Operations- und Prozedurenschlüssel" (OPS) 2014, the German standard for process codes and interventions, was used to determine surgical extirpation methods. Categorical qualifiers were defined to analyze the data provided by the Robert Koch Institute (RKI), the German Federal Bureau of Statistics (DESTATIS; Hospital and Causes of Death Statistics), the population-based Cancer Register of Bavaria. A systematic search was done of the MEDLINE database and the Cochrane collaboration, covering the period from 1966 until November 2014. The incidence of uterine sarcoma and uterine fibroids in uterine surgery was compared to the literature and with the different registries. The incidence of uterine sarcoma in 2010, standardized for age, was 1.53 for Bavaria, or 1.30 for every 100 000 women, respectively, averaged for the years 2002-2011, and 1.30 for every 100 000 women in Germany. The mean incidence collated from various surveys was 2.02 for every 100 000 women (0.35-7.02; standard deviation 2.01). The numbers of inpatient surgical procedures such as myoma enucleation, morcellation, hysterectomy or cervical stump removal to treat the indication "uterine myoma" have steadily declined in Germany across all age groups (an absolute decrease of 17 % in 2012 compared to 2007). There has been a shift in the preferred method of surgical access from an abdominal/vaginal approach to endoscopic or endoscopically assisted procedures to treat uterine fibroids, with the use of morcellation increasing by almost 11 000 coded procedures in 2012. Based on international statements (AAGL, ACOG, ESGE, FDA, SGO) on the risk of uterine sarcoma as an coincidental finding during uterine fibroid surgery and the associated risk of a deterioration of prognosis (in the case of morcellation procedures), this overview presents the opinion of the DGGG in the form of four Statements, five Recommendation and four Demands.

Progress has been made in the treatment of metastatic breast cancer in recent decades, but very few therapies use patient or tumor-specific characteristics to tailor individualized treatment. More than ten years after the publication of the reference human genome sequence, analysis methods have improved enormously, fostering the hope that biomarkers can be used to individualize therapies and offer precise treatment based on tumor and patient characteristics. Biomarkers at every level of the system (genetics, epigenetics, gene expression, micro-RNA, proteomics and others) can be used for this. This has led to changes in clinical study designs, with drug developments often only focusing on small or very small subgroups of patients and tumors. The screening and registration of patients and their molecular tumor data has therefore become very important for the successful completion of clinical studies. This new form of medicine presents particular challenges for patients and physicians. Even in this new age of genome-wide analysis, the focus should still be on the patients' quality of life. This review summarizes recent developments and describes how the PRAEGNANT study network manages the aforementioned medical challenges and changes to create a professional infrastructure for patients and physicians.

In a large and heavily networked specialty like gynaecology it is a particular challenge with regard to future status to achieve excellent patient care, research and teaching. At the same time not only hospitals but also research facilities are experiencing increasing pressure from performance and competition sides in terms of survival and further development on the clinical, scientific and economic fronts. The numerous changes, including paradigm shifts, in medicine, society, the health-care system and scientific innovations present new challenges to the specialty. This leads to questions about priority, problem areas and weaknesses as well as to new opportunities for the field and the overall question if it will be possible to meet the paradigm shifts and problems by the creation of new structures. In the light of the need for and the potential of design measures, this article presents a SWOT analysis of the specialty's situation as a whole and in particular for gynaecology in German universities. One sees additional demands that add up to an expansion of the tasks. At the same time the shortage of new recruits becomes apparent. A broadening of the perspectives on women's health and individualised medicine come into focus. Partial solutions include new supporting structures, capacity measurements as well as even structural options. In particular, the department structure, that is common abroad, opens an opportunity for specialisation while maintaining unity for a broader further training and strengthened research. Chances and strengths of the specialty are especially effective in coordinated and concerted activities.

Introduction: The EvaluateTM study (Evaluation of therapy management and patient compliance in postmenopausal hormone receptor-positive breast cancer patients receiving letrozole treatment) is a prospective, non-interventional study for the assessment of therapy management and compliance in the routine care of postmenopausal women with invasive hormone receptor-positive breast cancer receiving letrozole. The parameters for inclusion in the study are presented and discussed here. Material and Methods: Between January 2008 and December 2009 a total of 5045 patients in 310 study centers were recruited to the EvaluateTM study. Inclusion criteria were hormone receptor-positive breast cancer and adjuvant treatment or metastasis. 373 patients were excluded from the analysis for various reasons. Results: A total of 4420 patients receiving adjuvant treatment and 252 patients with metastasis receiving palliative treatment were included in the study. For 4181 patients receiving adjuvant treatment, treatment with the aromatase inhibitor letrozole commenced immediately after surgery (upfront). Two hundred patients had initially received tamoxifen and started aromatase inhibitor treatment with letrozole at 1-5 years after diagnosis (switch), und 39 patients only commenced letrozole treatment 5-10 years after diagnosis (extended endocrine therapy). Patient and tumor characteristics were within expected ranges, as were comorbidities and concurrent medication. Conclusion: The data from the EvaluateTM study will offer a good overview of therapy management in the routine care of postmenopausal women with hormone receptor-positive breast cancer. Planned analyses will look at therapy compliance and patient satisfaction with how information is conveyed and the contents of the conveyed information.

Laparoscopy is playing an increasingly important role in gynecologic oncology. The benefits of minimally invasive surgery for oncology patients and the quality of this treatment are well documented. Outcomes and quality of minimally invasive surgical procedures to treat cervical cancer were evaluated based on retrospective and case-control studies; outcomes and quality after minimally invasive treatment für early-stage low-risk endometrial cancer were also assessed in prospective randomized studies. If indicated, laparoscopic lymphadenectomy is both technically feasible and oncologically safe. Adipose patients in particular benefit from minimally invasive procedures, where feasible. The potential role of laparoscopy in neoadjuvant therapy for ovarian cancer and in surgery for early-stage ovarian carcinoma is still controversially discussed and is currently being assessed in further studies. Using a minimally invasive approach in gynecologic oncology procedures demands strict adherence to oncological principles and requires considerable surgical skill.

Termination of pregnancy after the first trimester is generally carried out by medical induction. Question: The aim of this study is to investigate the effect of mifepristone before administration of the prostaglandin derivative on induction time. Material and Methods: We analysed 333 medically indicated terminations after the first trimester under the terms of § 218 a Para. 2 of the German Criminal Code, in which the prostaglandin derivatives misoprostol, gemeprost or dinoprostone were administered with or without pre-treatment with 600 mg of mifepristone. The time interval between the initial administration of prostaglandin and delivery was investigated. Using uni- and multivariate regression analysis, the effect of maternal age, body mass index, gravidity and parity, previous Caesarean sections, gestational age and the induction regimen on the induction time were analysed. Results: The average induction time was significantly shortened with mifepristone (15.1 ± 11.9 hours with mifepristone vs. 25.3 ± 24.2 hours without mifepristone [p < 0.001]). The combination of mifepristone and misoprostol was most frequently used and proved to be the most effective regimen, reducing the induction period to 13.6 ± 10.3 hours. Besides pre-treatment with mifepristone, gestational age and a history of delivery without Caesarean section were significant influencing factors in reducing the induction time. Conclusion: The induction interval can be significantly shortened by the prior administration of mifepristone. The combination of mifepristone and misoprostol or gemeprost is the most effective regimen for the medical termination of pregnancy.

Purpose: Inflammatory myofibroblastic tumours (IMT) are a subcategory of inflammatory pseudotumours (IPT). They arise most commonly in the abdominopelvic region, lung and retroperitoneum, but virtually any anatomical site may be involved. Predominantly children and adolescents are affected and there is a tendency for local recurrence. In the literature up to the present, 20 patients have been reported with an IPT/IMT of the breast. We would like to present another patient with this unusual tumour entity of the breast and discuss the literature. Patient and Examinations: A 23-year-old woman presented with a painless lump in her left breast. There was no history of breast cancer in her family. Sonography showed a hypoechoic heterogeneous solid mass with irregular margins. A core needle biopsy revealed a tumour of high cellularity and a densely collagenous background. Immunohistochemically, the spindle-shaped cells were immunoreactive to smooth muscle actin and ALK-1 protein. Additional FISH analysis proved ALK rearrangements on chromosome 2p23 leading to the diagnosis of an IMT. Wide surgical excision was performed with no evidence of local recurrence after 12 months. Conclusion: Three of the above mentioned 20 patients with IMT/IPT of the breast developed a recurrent tumour, none presented with distant metastasis. A significant recurrence rate of 15 % leads to a clinically and sonographically close follow-up in these patients.

Patients are expected to be increasingly competent about health issues, and patient self-determination is on the rise. This makes it ever more necessary to provide high quality information which is increasingly being offered to patients at all levels of the healthcare system. One example of a regionally available information service offered to patients is the Women's Academy, created 10 years ago, at the University Women's Hospital Tübingen in association with the Institute for Women's Health. The Women's Academy also serves as a forum and an outreach hub for the (cancer) centres of the Women's Hospital. The topics addressed include problematic areas in medicine and problems in coping with health and disease and additionally reflect the emergence of various patient interests and needs over time. The communication between physician and patient is central to the promotion of health literacy and individualised medicine. Regionally available services like the Women's Academy offer complementary benefits and are able to reach vulnerable groups of women who have little or no access to online information.

Introduction: The German DRG system is annually adapted to the changing services provided. For the further development, the self-governing body and its DRG Institute (InEK) depend on participation of the users. Methods: For one of the DRG evaluation projects initiated by DGGG, cost and performance data for the year 2011 from 16 hospitals were available. After plausibility checks and corrections, analyses for service and cost homogeneity were performed. In cases of inadequate DRG-representation attributes were sought that would make an appropriate reimbursement possible. Conspicuities and potential solutions were checked for clinical plausibility. Results: 44 concrete modification proposals for further development of the G-DRG system were formulated and submitted in due time to the InEK. In addition, 3 modification proposals were addressed to the German Institute for Medical Documentation and Information (Deutsches Institut für Medizinische Dokumentation und Information, DIMDI) for further development of the diagnosis classification ICD-10-GM. For all modification proposals care was taken to minimise misdirected incentives and to reduce the potential for disputes with the cost bearers and their auditors services in settlements. Discussion: The publication of the G-DRG system 2014 shows which modification proposals have been realised. Essentially, an appropriate redistribution of the resources among the gynaecological and obstetrics departments is to be expected. The financial pressure that is caused by the generally inadequate financing of hospitals will not be reduced by a further development of the G-DRG system.

Background: The impact of the European Working Time Directive and subsequent collective wage agreements for doctors from 2006 onwards were substantial. So far, no systematic evaluation of their application in Germany has been performed. We evaluated the impact four years after implementation of new shift models in a University Hospital for Gynaecology and Obstetrics (UHGO). Methods: A new shift model was created together with doctors of Tübingen UHOG in 2007 and implemented in 2008. Documentation of working hours has hence been done electronically. Adherence to the average weekly working time limit (AWTL) and the maximum of 10 h daily working time (10 h-dwt) was evaluated, as well as staffing costs in relation to case-weight points gathered within the German DRG (diagnosis related groups) System. Results: Staff increased from a mean of 44.7 full time equivalent (FTE) doctors in 2007 to 52.5 FTE in 2009, 50.8 in 2010, and 54.5 in 2011. There was no statistically significant difference of the monthly staff expenditures per case-weight between the years 2009 or 2010 vs. 2007. 2011, however, was significantly more expensive than 2007 (p = 0.02). The internal control group (five other departments of the university hospital) did not show an increase during the same period. AWTL were respected by 90, 96, and 98 % in 2009, 2010, and 2011, respectively. Of all shifts 10 h-dwt was exceeded by 7.4 % in 2009, 1.3 % in 2010, and 2.6 % in 2011, with significant differences between 2009 and both, 2010 and 2011 (p < 0.001), and between 2010 and 2011 (p = 0.02). Discussion: AWTL and 10 h-dwt could be continuously respected quite well after implementation of the new shift model without increasing the cost/earnings ratio for the first two years. However, in 2011 the ratio increased significantly (p = 0.02).

Introduction: Quality reporting was initially implemented to offer a better means of assessing hospitals and to provide patients with information to help them when choosing their hospital. Quality reports are published every 2 years and include parameters describing the hospital's structure and general infrastructure together with specific data on individual specialised departments or clinics. Method: This study investigated the 2010 quality reports of German university hospitals published online, focussing on the following data: number of inpatients treated by the hospital, focus of care provided by the unit/department, range of medical services and care provided by the unit/department, non-medical services provided by the unit/department, number of cases treated in the unit/department, ICD diagnoses, OPS procedures, number of outpatient procedures, day surgeries as defined by Section 115b SGB V, presence of an accident insurance consultant and number of staff employed. Results: University gynaecology clinics (UGCs) treat 10 % (range: 6-17 %) of all inpatients of their respective university hospital. There were no important differences in infrastructure between clinics. All UGCs offered full medical care and were specialist clinics for gynaecology (surgery, breast centres, genital cancer, urogynaecology, endoscopy), obstetrics (prenatal diagnostics, high-risk obstetrics); many were also specialist clinics for endocrinology and reproductive medicine. On average, each clinic employs 32 physicians (range: 16-78). Half of them (30-77 %) are specialists. Around 171 (117-289) inpatients are treated on average per physician. The most common ICD coded treatments were deliveries and treatment of infants. Gynaecological diagnoses are underrepresented. Summary: UGCs treat 10 % of all inpatients treated in university hospitals, making them important ports of entry for their respective university hospital. Around half of the physicians are specialists. Quality reports offer little information on the differences in competencies or medical specialties. The statutory quality reports are not useful for patients and referring physicians when choosing a clinic.

Purpose: Evidence regarding distinguishing characteristics of women with symptomatic leiomyomas during pregnancy who undergo myomectomy during pregnancy and those who respond to conservative treatment is sparse because it mostly derives from case reports and small patient series. As the first of its type, the present study analyzed the characteristics of women with symptomatic leiomyomas treated with myomectomy during pregnancy and those treated conservatively. Methods: We performed a computer search of medical records from 1 January 2001 to 31 March 2011 using the International Classification of Diseases Codes for pregnancy, myomectomy and leiomyomas during pregnancy. Results: 27 patients were admitted during pregnancy directly related to leiomyomas; 17 of the 27 patients received conservative treatment for symptomatic leiomyomas, and 10 patients had surgery during pregnancy: 3 had undergone diagnostic surgical procedures and 7 myomectomy. Perioperative and postoperative morbidity was low in all women in our sample. Conclusion: In our pilot study, myomectomy during pregnancy was safely performed in carefully selected patients, with subserosal or pedunculated leiomyomas that failed to respond to conservative treatment, with low perioperative and postoperative morbidity.

With the development of a National Cancer Plan published in 2012, Germany has followed the recommendations of the WHO and the EU. The first area of action listed in Germany's National Cancer Plan is improving the early detection of cancer. Both citizens and medical specialists are encouraged to take responsibility themselves and contribute to the efforts being made to meet the challenge of cancer. Screening for cervical cancer has long been an integral part of the German Directive for the Early Detection of Cancer and now - following the recommendations given in the European Guideline - an organised screening approach shall be developed to maximise the benefits and minimise the risks through a partial reorganisation of existing structures. Before this can be rolled out nationwide, it will be necessary to check the feasibility and suitability of new contents and organisational structures. The Federal Joint Committee which is largely responsible for the process according to the draft law on the implementation of the National Cancer Plan has emphasised the importance of evidence-based medicine and of collaboration between the autonomous governing bodies within the healthcare system to obtain viable results. For medical specialists, the follow-on question is which areas will need more research in future. New process steps need to be developed and verified to see whether they offer evidence which will support defined approaches or whether such evidence needs to be newly compiled, e.g. by testing invitation procedures for screening in trial schemes. The experience gained during the implementation of the existing directive on early detection of cancer should be integrated into the new process. Research initiated by specialists could encourage the development of a new version of the Directive for the Early Detection of Cancer suitable for the Germany's healthcare system.

Purpose: The aim of our study was to investigate the rate of secondary carcinomas in patients with endometrial carcinoma (EC). In particular, we wanted to describe the subset of patients with endometrial and simultaneous ovarian carcinoma (OC), including outcomes. The study also compared patients with EC and ovarian metastasis with patients with EC and simultaneous OC. Patients and Methods: Data from 251 patients with primary endometrial carcinoma who underwent surgery in the years 2005-2009 at the Department of Obstetrics and Gynaecology, University of Tübingen, were analysed retrospectively. Results: A total of 28 patients (11.1 %) had a secondary carcinoma: 18 patients (7.1 %) had OC; 9 (3.5 %) patients had a history of breast cancer, and one patient (0.4 %) respectively had simultaneous carcinoma of the vulva or bladder. 14 patients (5.5 %) had advanced stage EC with ovarian metastasis or, in one case, metastasis to the ovarian tube. Patients with ovarian metastasis had a mean age of 71.2 ± 9.2 years at primary diagnosis, making them significantly older compared to patients with EC and simultaneous OC (55.3 ± 11.8 years, p < 0.001). Moreover, patients with ovarian metastasis significantly more often had EC with a higher tumour grade (grade 1: 0, grade 2: 21.4 %, grade 3: 78.6 %) compared to patients with simultaneous EC and OC (grade 1: 11.1 %, grade 2: 77.8 %, grade 3: 11.1 %; p < 0.001). Conclusion: Almost one in 10 patients with EC had a secondary carcinoma. The most common secondary carcinoma was OC followed by breast cancer. This should be taken into account in the diagnosis and therapy of patients with EC. Patients with simultaneous EC and OC were significantly younger than patients with EC and ovarian metastasis. In addition, their tumour had better prognostic features: thus, the tumour grade of the EC was significantly lower. Overall, the prognosis for patients with synchronous EC and OC is better than that for patients with EC and ovarian metastasis.

For answering the question at which hysteroscopical procedures an intraoperative screening method is necessary to avoid a fluid overload and whether a beginning fluid absorption can be diagnosed early by adding ethanol to the distension medium, a prospectively randomised comparative study of ablative versus non-ablative operative hysteroscopy with differing ethanol concentrations was performed (n = 120). Purisole (a mannit/sorbit solution) was used a distension medium. The measuring parameters (breath alcohol, amount of absorbed fluid, haematocrit and haemoglobin values, central venous pressure, heart frequency) were intraoperatively determined at 5-minute intervals. The results of the study show that with those hysteroscopical procedures during which the endometrium is not or only minimally injured (e.g. syneciolysis, hysteroscopic proximal tubal catheterisation). Intraoperative screening is not necessary due to the low absorbing amounts. With hysteroscopical procedures such as resection of myoma, endometrium ablation and septum resection, however, an addition of ethanol of 2% to the distension medium has proved useful, because with this method absorption amounts of 400 ml and more can be detected by positive values of breath alcohol. As the result of a further absorption of fluid, delayed in time compared to the first positive value of breath alcohol, there is an increase in central venous pressure and hyponatraemia. Intraoperative ethanol monitoring is a non-invasive procedure which can be performed during ablative-operative hysteroscopies and has no negative influence on the course of the intervention and the general condition of the patients.

The plasminogen activator system plays a key role in the proteolysis of malignant tumours. In 155 patients with primary breast cancer levels from PAI-1 and uPA were measured in cytosol with monoclonal antibodies and by an enzyme-linked immunosorbent assay. 35 tumour tissue samples form benign breast were also examined. Malignant tumours contain higher levels of PAI-1 (8.6 ng/mg) than benign tumours (1.28 ng/mg) (p < 0.01). Also the median level of uPA was significantly higher (p < 0.01) in malignant tissue (2.38 ng/mg) in comparison to benign disease (0.54 ng/mg). No correlation was found between the proteases and the classical prognostic parameters like axillary lymph node involvement, tumour size and menopausal status. However, a significant correlation (p < 0.01) was found in tumours with lymphangiosis carcinomatosa, negative hormone receptors, grade III tumour cells and high S-phase fractions (> 5%). After a median follow-up of 46 months we found that high levels of PAI-1 correlated with short DFS (p = 0.0005) and OAS (p = 0.003). However, in the Cox multivariate regression analysis only PAI-1 was significantly independent for OAS and could therefore give additional information. We conclude that levels from PAI-1 antigen measured in cytosol of primary breast cancer is an independent prognostic parameter to identify patients with high and low risk for relapse and for individualised treatment.

Preoperative ultrasound as well as intraoperative laparoscopic diagnosis have both their limits, a fact that might be significant for laparoscopic surgical management. In particular, since in this surgical domain, where almost everything has become technically feasible, the operator must decide what is to the benefit of the patient. A possible solution could be laparoscopic ultrasound, i.e. ultrasound diagnosis per laparoscopy at the very site of the lesion. The advantages are evident. Due to the closeness to the organ to be examined, the frequency of the scan head can be extremely high, resulting in better resolution. Also, structures could be visualized by ultrasound which e.g., due to adhesions cannot be seen with the laparoscope. Moreover, ultrasound offers a view into the structures which can be seen only from the exterior with the laparoscope. To perform these examinations we used a specially designed scanhead (Toshiba): Instead of the optical system a crystal array was inserted into a conventional gastroscope. The result was a high resolution 7.5 MHz linear array at the distal end of a freely movable gastroscope. Colour doppler sonography is feasible with this scanhead. We examined 19 patients, 16 of them with ovarian tumours, and attempted visualization of the uterine myometrium/endometrium as well as of the liver. In six cases of ovarian tumours in which only cystic structures were found by preoperative transvaginal sonography, laparoscopic ultrasound additionally revealed solid inner structures. In 5 cases direct laparoscopic view of the ovarian lesions was impossible due to severe adhesions. They were, however, easily detected by intraoperative ultrasound.(ABSTRACT TRUNCATED AT 250 WORDS)

Within the framework of "minimal access surgery" a prospective randomised study was initiated at the Dept. of Obstetrics and Gynaecology of Heidelberg University to examine the feasibility of endoscopical abdominal Burch colposuspension for stress incontinence (II-III), at laparoscopy and "retziusscopy". Further, also prospectively randomised, two suspension techniques: needle suspension and suspension by means of alloplastic material with stapler fixation, were compared, irrespective of the endoscopic approach chosen, especially because long-term results of our study population on colposuspension with fibrin glue which are now available, are below expectations, worse than those obtained with conventional techniques. Except for a bladder lesion (during laparoscopic dissection of the space of Retzius) no intra- or postoperative complications occurred in the pilot study group of 20 patients. Both types of endoscopic access proved technically feasible, and presented the typical advantages of minimal access surgery such as short hospitalization and rapid recovery. Short-term follow-up (2-12 months) showed subjective and objective results (continence in 18/20 patients), comparable to conventional abdominal procedures at laparotomy. Detailed evaluation of subgroups is not yet possible, since the number of patients it still too small and follow-up too short.

Whilst endoscopic surgical procedures are getting increasingly more complex, in the various surgical disciplines mono- and bifunctional instruments are only slowly being replaced by multifunctional ones. Therefore a complex, intelligent system was developed, the central part of which is a multifunctional instrument. All basic functions necessary for surgical laparoscopy are integrated and comprise: cutting electrodes (unipolar and bipolar) which can be advanced or retracted pneumatically; coagulation forceps with mechanical control; and irrigation and suction devices. All 5 mm instruments can be used and there is an option for others, such as laser or aqua-dissection. The various functions are controlled via the handle of the multifunctional instrument which is connected to the electronic control unit, the MULTILAP system, which supplies the energy, material, and information flow required. In vivo standardised experiments in pigs were first performed to test the new instrument. Operation time was reduced by more than 20% when compared with the same procedure performed conventionally, during which frequent changing of instruments was necessary. Clinical application, without complications in all 30 patients (uterus preserving procedures or reconstructive tubo-ovarian surgery) confirmed the advantages of a multifunctional device, with optimised cutting and coagulation of vessels more than 1-2 mm in diameter, and reduced duration of operation. Safety and ergonomics were improved. Thus, an electronically controlled instrument with multifunctional working channels for lasers, ultrasound appliances, or mechanical instruments is available for application in all domains of operative laparoscopy.

The technical feasibility of the laparoscopic and extraperitoneal approach to the Burch colposuspension for treatment of grade II and III (moderate to severe) stress incontinence was examined in a randomised prospective study. Irrespective of the endoscopic access, two suspension techniques, namely conventional suture and stapler fixation of alloplastic materials, were compared. A total of 20 patients entered this preliminary evaluation. Three complications occurred; a bladder perforation (during laparoscopic dissection of the space of Retzius), a postoperative detrusor instability and transient urinary retention. Both the endoscopic approaches and the suspension procedures employed proved feasible and safe, and presented the advantages of a "minimal access" procedure, with short hospitalisation and rapid recovery. Short-term follow-up (6-12 months) showed subjective and objective results comparable to those of the conventional abdominal Burch colposuspension. Detailed evaluation of the subgroups is not yet feasible, as the number of patients in this preliminary evaluation was too small and follow-up too short. Final evaluation of the entire study population and long-term follow-up will be necessary before these procedures can be generally offered as a therapeutic alternative.

Hysteroscopic endometrial ablation under maximal anaesthesiological surveillance was performed in 34 high-risk patients to avoid hysterectomy. It was a collective of patients with heavy thrombo-embolic or thrombotic disease, either under permanent anticoagulation due to residual disease or multiple endoprosthetic treatment, or with endogenous coagulopathy. In all these women, hysterectomy was either a relative or an absolute contraindication. In 22 patients, treatment resulted in complete amenorrhoea or at least hypomenorrhoea (without menometrorrhagia) respectively cyclic spotting. In 6 further patients, amenorrhoea was achieved after a repeat procedure. Endometrial ablation was thus successful in 28 of 34 cases. In these patients, hysterectomy with the risk of major or even lethal complications, could thus be avoided. Hysterectomy, however, had to be performed in 2 women with extensive adenomyosis uteri interna. Within two respectively three years after endometrial ablation, two other patients died from causes unrelated to the surgical intervention (cardiac infarction, cerebral haemorrhage). Follow-up ranged from 1 to 5 years. Hysteroscopic endometrial ablation proved an effective therapeutic option in this selected group of patients. Other indications require further study.

The operative treatment of stress incontinence with the Marshall-Marchetti-Krantz procedure has proved effective. A new, endoscopic modification of this procedure is presented here, based on the principle of vesico-urethral suspension with fibrin glueing. Open abdominal surgery is replaced by retziusscopy and a minimal invasive endoscopic intervention in the Retzius' cavity.

The specific disadvantage of the Vecchietti technique for construction of a vagina in cases of vaginal agenesis is the need for laparotomy. We describe an endoscopically assisted construction of a vagina by a variation of this method and report on the first five cases operated on without any complications and with good functional results.

The extremely small ultrasound transducers of the intraluminal ultrasound instruments, introduced via catheters, enable diagnosis to be made inside hollow organs. In order to test the possible uses and indications for this new method in gynaecology, we conducted preliminary examinations in the diagnosis of the uterus and tubes. We employed an intraluminal instrument supplied by Dornier. The intraluminal transducers of this instrument have a diameter of 3.5 and 5 F. Following in-vitro examinations, hysteroscopy and laparoscopy/laparotomy were performed in 15 patients during which the transducer was pushed up via the cervix uteri to the tubes with full vision. This was successful in all 15 patients; in 9 cases the transducer could be pushed as far as the distal end. The tubal walls were examined in detail by this method and for the first time it became possible to achieve functional diagnosis of the motility of the tubes. Strictures can be visualised. The endometrium of the uterus, however, cannot as yet be diagnosed exactly by the present-day state of examination technique. If image quality can be further improved, this method will be the first to enable a functional diagnosis of the tubes and the uterus.

Malignant tumours can be differentiated from the benign ones by their vascular blood supply. We employed three methods to analyse the blood flow: the angiodynograph, the duplex system, and the continuous-wave Doppler method, and measured the blood flow in 151 patients on the preoperative day. Histology revealed a malignoma in 92 cases and a benign tumour in 59 cases. It was found, that in more than 90% of the malignomas, a high blood flow was identified in or around the tumour by means of the colour method (angiodynography), which could be quantified by the pulsed-wave Doppler. A significantly lower blood flow was evident in the benign tumours with a markedly increased resistance index (by 80%) established by means of the pulsed-wave Doppler. Continuous-wave (CW) Doppler showed a significantly higher blood flow with almost all malignomas in the entire breast, than was the case with benign changes. Our studies showed, that the enhanced blood flow in and around malignant tumours can be visualised by means of update technology, angiodynography being particularly suitable for demonstrating the flow by the B-mode. Quantification, however, is, at present, only possible by employing the duplex method with pulsed-wave Doppler. CW Doppler is suitable only for blood flow diagnosis of the entire organ, but it requires great precision of working method and is time consuming; tumour blood flow cannot be visualised on-target by this method.

Local recurrences of carcinomas of the breast and genitals are a severe psychic and physical strain on the patients. Continuous confrontation with an often visible and generally painful tumour manifestation is an indication for palliative treatment, if other oncological therapies can no longer be employed. In these cases, the possibility of laser use represents a new therapeutic approach. In a pilot study at the University of Heidelberg, Department of Obstetrics and Gynaecology, a palliative laser therapy was performed on 45 patients with locally recurrent carcinomas of the breast (n = 29) and genitals (n = 16). Carbon dioxide and Nd:YAG lasers were utilized for tumour resection, vaporisation and coagulation. This new concept, the combined application of both wavelengths has been proved to be most efficient.

Transvaginal ultrasound provides important detailed information, which cannot be obtained by routine manual vaginal examination. By measuring the outside-inside distance (from os externum to os internum), we can determine the actual length of the cervix. By depicting the cervical canal, we can identify early dilatation. Visualizing the os internum with a possible opening, forming a conus, helps reveal an incompetent cervix. A total of 485 measurements of the cervix was carried out. Fifty patients with normal clinical findings between 28 and 32 weeks of pregnancy were compared to the same number of patients in the 28th to 32nd week of pregnancy, with the clinical diagnosis of an incompetent cervix. A cervical length of 46.3-39.3 mm was found in normal pregnancies, and a length of 34.0-21.4, when a clinically incompetent cervix had been diagnosed, a difference of 12.3-17.9 mm.