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For patients with locally advanced or metastatic breast cancer, new and effective therapies such as CDK4/6 inhibitors, PARP inhibitors and a PD-L1 inhibitor have been introduced in recent years. This review presents an update on the available studies with their data. In addition, two innovative anti-HER2 therapies are presented (trastuzumab-deruxtecan and tucatinib) for which the results from new studies have been reported. Molecular tests offer the possibility of defining patient populations or also monitoring courses of therapy. This can help identify patients with specific characteristics in order to provide them with individually targeted therapy within the framework of studies. In a large study, the benefit of such a biomarker study was able to be described for the first time., Competing Interests: Conflict of Interest/Interessenkonflikt A. D. H. received speaker and consultancy honoraria from AstraZeneca, Genomic Health, Roche, Novartis, Celgene, Lilly, MSD, Eisai, Teva, Tesaro, Daiichi-Sankyo, Hexal and Pfizer. F. O. received speaker and consultancy honoraria from Amgen, AstraZeneca, Bayer, BMS, Boehringer-Ingelheim, Chugai, Celgene, Cellex, Eisai, Gilead, Hexal, Ipsen, Janssen-Cilag, Merck, MSD, Novartis, Novo Nordisk, Riemser, Roche, Servier, Shire, Tesaro, Teva. H.-C. K. received honoraria from Carl Zeiss meditec, TEVA, Theraclion, Novartis, Amgen, Astra Zeneca, Pfizer, Janssen-Cilag, GSK, LIV Pharma, Roche, Genomic Health, Theramex, ClinSol and onkowissen.de, travel support from Carl Zeiss meditec, Novartis, Amgen, Astra Zeneca, Pfizer LIV Pharma, Genomic Health, Tesaro and Daiichi-Sankyo and owns stock from Theraclion and Phaon Scientific. 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. H. T. received honoraria from Novartis, Roche, Celgene, Teva, Pfizer and travel support from Roche, Celgene and Pfizer. J. E. received honoraria from Astra Zeneca, Roche, Celgene, Novartis, Lilly, Pfizer, Pierre Fabre, Teva and travel support from Celgene, Pfizer, Teva and Pierre Fabre. M. P. L. has participated on advisory boards for AstraZeneca, Lilly, MSD, Novartis, Pfizer, Eisai, Genomic Health and Roche and has received honoraria for lectures and medical education activities MSD, Lilly, Roche, Novartis, Pfizer, Genomic Health, AstraZeneca, medac, onkowissen.de, ClinSol 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 and Eisai, Lilly, Tesaro and Nektar. E. B. received honoraria from Novartis, Hexal and onkowissen.de for consulting, clinical research management or medical education activities. 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. W. J. received honoraria and research grants from Novartis, Roche, Pfizer, Lilly, AstraZeneca, Chugai, Sanofi, Daiichi-Sankyo, Tesaro. F. S. participated on advisory boards for Novartis, Lilly, Amgen and Roche and received honoraria for lectures from Roche, AstraZeneca, MSD, Novartis and Pfizer. A. W. participated on advisory boards for Novartis, Lilly, Amgen, Pfizer, Roche, Tesaro, Eisai, Celgene, Teva, Hexal, AstraZeneca, Sirtex, MSD and received honoraria for lectures from Novartis, Pfizer, Aurikamed, RocheAmgen, Eisai, Lilly, AstraZeneca, Genomic Health, ClinSol, onkowissen.de. D. L. received honoraria from Amgen, AstraZeneca, ClinSol, Celgene, Lilly, Loreal, MSD, Novartis, onkowissen.de, Pfizer, Tesaro, Teva. 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. M. T. has participated on advisory boards for AstraZeneca, Lilly, MSD, Novartis, Pfizer, Genomic Health and Roche and has received honoraria for lectures from MSD, Lilly, Roche, Novartis, Pfizer, Genomic Health, and AstraZeneca. M. W. has participated on advisory boards for AstraZeneca, Lilly, MSD, Novartis, Pfizer and Roche. J. H. reports receiving speakers bureau honoraria from Celgene, Novartis and Roche, and is a consultant/advisory board member for Amgen, Celgene, Novartis and Roche./ A. D. H. hat Referenten- und Beraterhonorare von AstraZeneca, Genomic Health, Roche, Novartis, Celgene, Lilly, MSD, Eisai, Teva, Tesaro, Daiichi-Sankyo, Hexal und Pfizer erhalten. F. O. hat Referenten- und Beraterhonorare von Amgen, AstraZeneca, Bayer, BMS, Boehringer-Ingelheim, Chugai, Celgene, Cellex, Eisai, Gilead, Hexal, Ipsen, Janssen-Cilag, Merck, MSD, Novartis, Novo Nordisk, Riemser, Roche, Servier, Shire, Tesaro und Teva erhalten. H.-C. K. hat Honorare von Carl Zeiss meditec, Teva, Theraclion, Novartis, Amgen, AstraZeneca, Pfizer, Janssen-Cilag, GSK, LIV Pharma, Roche, Genomic Health, Theramex, ClinSol und onkowissen.de sowie Reiseförderungen von Carl Zeiss meditec, Novartis, Amgen, AstraZeneca, Pfizer LIV Pharma, Genomic Health, Tesaro und Daiichi Sankyo erhalten und hält Aktien von Theraclion und Phaon Scientific. P. A. F. hat Honorare von Novartis, Pfizer, Roche, Amgen, Celgene, Daiichi-Sankyo, AstraZeneca, Merck-Sharp & Dohme, Eisai, Puma und Teva erhalten. Die Forschungsaktivitäten seiner Einrichtung werden finanziell von Novartis und Biontech unterstützt. H. T. hat Honorare von Novartis, Roche, Celgene, Teva und Pfizer sowie Reiseförderungen von Roche, Celgene und Pfizer erhalten. J. E. hat Honorare von AstraZeneca, Roche, Celgene, Novartis, Lilly, Pfizer, Pierre Fabre und Teva sowie Reiseförderungen von Celgene, Pfizer, Teva und Pierre Fabre erhalten. M. P. L. war Mitglied von Beratungsgremien für AstraZeneca, Lilly, MSD, Novartis, Pfizer, Eisai, Genomic Health und Roche und hat Honorare für Vorträge sowie medizinische Schulungen von MSD, Lilly, Roche, Novartis, Pfizer, Genomic Health, AstraZeneca, medac, onkowissen.de, ClinSol und Eisai erhalten. V. M. hat Referentenhonorare von Amgen, AstraZeneca, Celgene, Daiichi-Sankyo, Eisai, Pfizer, Novartis, Roche, Teva, Janssen-Cilag sowie Beraterhonorare von Genomic Health, Hexal, Roche, Pierre Fabre, Amgen, Novartis, MSD, Daiichi-Sankyo, Eisai, Lilly, Tesaro und Nektar erhalten. E. B. hat Honorare von Novartis, Hexal und onkowissen.de für Beratungstätigkeiten, die Leitung klinischer Forschungsvorhaben bzw. medizinische Schulungen erhalten. A. S. hat Honorare von Roche, Celgene, AstraZeneca, Novartis, Pfizer, Zuckschwerdt Verlag GmbH, Georg Thieme Verlag, Aurikamed GmbH, MCI Deutschland GmbH, bsh medical communications GmbH und promedicis GmbH erhalten. W. J. hat Honorare und Forschungsstipendien von Novartis, Roche, Pfizer, Lilly, AstraZeneca, Chugai, Sanofi, Daiichi-Sankyo und Tesaro erhalten. F. S. war Mitglied von Beratungsgremien für Novartis, Lilly, Amgen und Roche und hat Vortragshonorare von Roche, AstraZeneca, MSD, Novartis und Pfizer erhalten. A. W. war Mitglied von Beratungsgremien für Novartis, Lilly, Amgen, Pfizer, Roche, Tesaro, Eisai, Celgene, Teva, Hexal, AstraZeneca, Sirtex und MSD und hat Vortragshonorare von Novartis, Pfizer, Aurikamed, RocheAmgen, Eisai, Lilly, AstraZeneca, Genomic Health, ClinSol und onkowissen.de erhalten. D. L. hat Honorare von Amgen, AstraZeneca, ClinSol, Celgene, Lilly, Loreal, MSD, Novartis, onkowissen.de, Pfizer, Tesaro und Teva erhalten. T. N. F. war Mitglied von Beratungsgremien für Amgen, Daiichi-Sankyo, Novartis, Pfizer und Roche und hat Vortragshonorare von Amgen, Celgene, Daiichi-Sankyo, Roche, Novartis und Pfizer erhalten. M. T. war Mitglied von Beratungsgremien für AstraZeneca, Lilly, MSD, Novartis, Pfizer, Genomic Health und Roche und hat Vortragshonorare von MSD, Lilly, Roche, Novartis, Pfizer, Genomic Health und AstraZeneca erhalten. M. W. war Mitglied von Beratungsgremien für AstraZeneca, Lilly, MSD, Novartis, Pfizer und Roche. J. H. gibt an, Referentenvermittlungshonorare von Celgene, Novartis und Roche zu erhalten, und ist Berater/Mitglied von Beratungsgremien für Amgen, Celgene, Novartis und Roche.

The most important goal of treatment of patients with metastatic breast cancer is maintenance or even improvement of quality of life. In this setting, chemotherapy should be used with as much restraint as possible. If palliative chemotherapy is indicated, the taxane drug class is an established treatment option. The updated guidelines of the Gynaecological Oncology Working Group (AGO), Breast Committee, of the German Society for Gynaecology and Obstetrics (DGGG) and the German Cancer Society e. V. (DKG) provide recommendations with the greatest possible evidence on which of the licensed taxanes can be used in which treatment situation in the metastatic setting., Competing Interests: Conflict of Interest/Interessenkonflikt Oleg Gluz: lecture/consultancy fees: Celgene, Roche, Genomic Health, Amgen, Pfizer, Novartis, Lilly, Nanostring, Eisai, MSD; assistance with travel costs: Celgene, Roche, Daiichi Sankyo. Cornelia Liedtke: lecture/consultancy fees: Phaon Scientific, Novartis, Pfizer, Celgene, Roche, AstraZeneca, Lilly, Hexal, Amgen, Eisai, SonoScape; research sponsorship: Roche, Novartis, Pfizer; travel costs: Roche, Novartis. Marc Thil: lecture/consultancy fees: Amgen, AstraZeneca, Aurikamed, BiomʼUp, Celgene, Daiichi Sankyo, Eisai, Genomic Health, Hexal, Lilly, MCI, Medtronic, MSD, Myriad, Neodynamics, Norgine, Novartis, OnkoLive, OmniaMed, pfmMedical, Pfizer, Roche, Tesaro, Teva, RTI Surgical and research support by Genomic Health. Frederik Marme: lecture/consultancy fees: AstraZeneca, Tesaro, Roche, Novartis, Pfizer, PharmaMar, GenomicHealth, CureVac, Amgen, Eisai, MSD, Celgene, Clovis, Vaccibody, Immunomedics, Janssen-Cilag./ Oleg Gluz: Vortrags/Beratungshonorare: Celgene, Roche, Genomic Health, Amgen, Pfizer, Novartis, Lilly, Nanostring, Eisai, MSD; Reisekostenunterstützung Celgene, Roche, Daiichi Sankyo. Cornelia Liedtke: Vortrags/Beratungshonorare: Phaon Scientific, Novartis, Pfizer, Celgene, Roche, AstraZeneca, Lilly, Hexal, Amgen, Eisai, SonoScape; Forschungsförderung: Roche, Novartis, Pfizer; Reisekosten: Roche, Novartis. Marc Thil: Vortrags/Beratungshonorare: Amgen, AstraZeneca, Aurikamed, BiomʼUp, Celgene, Daiichi Sankyo, Eisai, Genomic Health, Hexal, Lilly, MCI, Medtronic, MSD, Myriad, Neodynamics, Norgine, Novartis, OnkoLive, OmniaMed, pfmMedical, Pfizer, Roche, Tesaro, Teva, RTI Surgical und Forschungsunterstützung von Genomic Health. Frederik Marme: Vortrags/Beratungshonorare: AstraZeneca, Tesaro, Roche, Novartis, Pfizer, PharmaMar, GenomicHealth, CureVac, Amgen, Eisai, MSD, Celgene, Clovis, Vaccibody, Immunomedics, Janssen-Cilag.

This review is intended to present the latest developments in the prevention and treatment of early breast cancer. The risk of breast cancer can be increasingly better characterised with large epidemiological studies on genetic and non-genetic risk factors. Through new analyses, the evidence for high-penetrance genes as well as for low-penetrance genes was able to be improved. New data on denosumab and atezolizumab are available in the neoadjuvant situation as is a pooled appraisal of numerous studies on capecitabine in the curative situation. There is also an update to the overall survival data of pertuzumab in the adjuvant situation with a longer follow-up observation period. Finally, digital medicine is steadily finding its way into science. A recently conducted study on automated breast cancer detection using artificial intelligence establishes the basis for a future review in clinical studies., Competing Interests: Conflict of Interest/Interessenkonflikt A. D. H. received speaker and consultancy honoraria from AstraZeneca, Genomic Health, Roche, Novartis, Celgene, Lilly, MSD, Eisai, Teva, Tesaro, Daiichi Sankyo, Hexal and Pfizer. F. O. received speaker and consultancy honoraria from Amgen, AstraZeneca, Bayer, BMS, Boehringer-Ingelheim, Chugai, Celgene, Cellex, Eisai, Gilead, Hexal, Ipsen, Janssen-Cilag, Merck, MSD, Novartis, Novo Nordisk, Riemser, Roche, Servier, Shire, Tesaro, Teva. H.-C.K . received honoraria from Carl Zeiss meditec, Teva, Theraclion, Novartis, Amgen, AstraZeneca, Pfizer, Janssen-Cilag, GSK, LIV Pharma, Roche, Genomic Health, Theramex, ClinSol and onkowissen.de, travel support from Carl Zeiss meditec, Novartis, Amgen, AstraZeneca, Pfizer LIV Pharma, Genomic Health, Tesaro and Daiichi Sankyo and owns stock from Theraclion and Phaon Scientific. 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. H. T. received honoraria from Novartis, Roche, Celgene, Teva, Pfizer and travel support from Roche, Celgene and Pfizer. J. E. received honoraria from AstraZeneca, Roche, Celgene, Novartis, Lilly, Pfizer, Pierre Fabre, Teva and travel support from Celgene, Pfizer, Teva and Pierre Fabre. M. P. L. has participated on advisory boards for AstraZeneca, Lilly, MSD, Novartis, Pfizer, Eisai, Genomic Health and Roche and has received honoraria for lectures and medical education activities from MSD, Lilly, Roche, Novartis, Pfizer, Genomic Health, AstraZeneca, medac, onkowissen.de, ClinSol and Eisai. V. M. received speaker honoraria from Amgen, AstraZeneca, 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 and Eisai, Lilly, Tesaro and Nektar. E. B. received honoraria from Novartis, Hexal and onkowissen.de for consulting, clinical research management or medical education activities. 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. W. J. received honoraria and research grants from Novartis, Roche, Pfizer, Lilly, AstraZeneca, Chugai, Sanofi, Daichi, Tesaro. F. S. participated on advisory boards for Novartis, Lilly, Amgen and Roche and received honoraria for lectures from Roche, AstraZeneca, MSD, Novartis and Pfizer. A. W. participated on advisory boards for Novartis, Lilly, Amgen, Pfizer, Roche, Tesaro, Eisai, Celgene, Teva, Hexal, AstraZeneca, Sirtex, MSD and received honoraria for lectures from Novartis, Pfizer, Aurikamed, Roche, Amgen, Eisai, Lilly, AstraZeneca, Genomic Health, ClinSol, onkowissen.de. D. L. received honoraria from Amgen, AstraZeneca, Celgene, ClinSol, Lilly, Loreal, MSD, Novartis, onkowissen.de, Pfizer, Tesaro, Teva 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. M.T . has participated on advisory boards for AstraZeneca, Lilly, MSD, Novartis, Pfizer, Genomic Health and Roche and has received honoraria for lectures from MSD, Lilly, Roche, Novartis, Pfizer, Genomic Health, and AstraZeneca. M. W. has participated on advisory boards for AstraZeneca, Lilly, MSD, Novartis, Pfizer and Roche. J. H. reports receiving speakers bureau honoraria from Celgene, Novartis, and Roche, and is a consultant/advisory board member for Amgen, Celgene, Novartis and Roche./ A. D. H. hat Referenten- und Beraterhonorare von AstraZeneca, Genomic Health, Roche, Novartis, Celgene, Lilly, MSD, Eisai, Teva, Tesaro, Daiichi Sankyo, Hexal und Pfizer erhalten. F. O. hat Referenten- und Beraterhonorare von Amgen, AstraZeneca, Bayer, BMS, Boehringer-Ingelheim, Chugai, Celgene, Cellex, Eisai, Gilead, Hexal, Ipsen, Janssen-Cilag, Merck, MSD, Novartis, Novo Nordisk, Riemser, Roche, Servier, Shire, Tesaro und Teva erhalten. H.-C.K . hat Honorare von Carl Zeiss meditec, Teva, Theraclion, Novartis, Amgen, AstraZeneca, Pfizer, Janssen-Cilag, GSK, LIV Pharma, Roche, Genomic Health, Theramex, ClinSol und onkowissen.de sowie Reiseförderungen von Carl Zeiss meditec, Novartis, Amgen, AstraZeneca, Pfizer LIV Pharma, Genomic Health, Tesaro und Daiichi Sankyo erhalten und hält Aktien von Theraclion und Phaon Scientific. P. A. F. hat Honorare von Novartis, Pfizer, Roche, Amgen, Celgene, Daiichi Sankyo, AstraZeneca, Merck-Sharp & Dohme, Eisai, Puma und Teva erhalten. Die Forschungsaktivitäten seiner Einrichtung werden finanziell von Novartis and Biontech unterstützt. H. T. hat Honorare von Novartis, Roche, Celgene, Teva und Pfizer sowie Reiseförderungen von Roche, Celgene und Pfizer erhalten. J. E. hat Honorare von AstraZeneca, Roche, Celgene, Novartis, Lilly, Pfizer, Pierre Fabre und Teva sowie Reiseförderungen von Celgene, Pfizer, Teva und Pierre Fabre erhalten. M. P. L. war Mitglied von Beratungsgremien für AstraZeneca, Lilly, MSD, Novartis, Pfizer, Eisai, Genomic Health und Roche und hat Honorare für Vorträge sowie medizinische Schulungen von MSD, Lilly, Roche, Novartis, Pfizer, Genomic Health, AstraZeneca, medac, onkowissen.de, ClinSol und Eisai erhalten. V. M. hat Referentenhonorare von Amgen, AstraZeneca, Celgene, Daiichi Sankyo, Eisai, Pfizer, Novartis, Roche, Teva und Janssen-Cilag sowie Beraterhonorare von Genomic Health, Hexal, Roche, Pierre Fabre, Amgen, Novartis, MSD, Daiichi Sankyo and Eisai, Lilly, Tesaro und Nektar erhalten. E. B. hat Honorare von Novartis, Hexal und onkowissen.de für Beratungstätigkeiten, die Leitung klinischer Forschungsvorhaben bzw. medizinische Schulungen erhalten. A. S. hat Honorare von Roche, Celgene, AstraZeneca, Novartis, Pfizer, Zuckschwerdt Verlag GmbH, Georg Thieme Verlag, Aurikamed GmbH, MCI Deutschland GmbH, bsh medical communications GmbH und promedicis GmbH erhalten. W. J. hat Honorare und Forschungsstipendien von Novartis, Roche, Pfizer, Lilly, AstraZeneca, Chugai, Sanofi, Daichi und Tesaro erhalten. F. S. war Mitglied von Beratungsgremien für Novartis, Lilly, Amgen und Roche und hat Vortragshonorare von Roche, AstraZeneca, MSD, Novartis und Pfizer erhalten. A. W. war Mitglied von Beratungsgremien für Novartis, Lilly, Amgen, Pfizer, Roche, Tesaro, Eisai, Celgene, Teva, Hexal, AstraZeneca, Sirtex und MSD und hat Vortragshonorare von Novartis, Pfizer, Aurikamed, Roche, Amgen, Eisai, Lilly, AstraZeneca, Genomic Health, ClinSol und onkowissen.de erhalten. D. L. hat Honorare von Amgen, AstraZeneca, Celgene, ClinSol, Lilly, Loreal, MSD, Novartis, onkowissen.de, Pfizer, Tesaro und Teva erhalten. T. N. F. war Mitglied von Beratungsgremien für Amgen, Daiichi Sankyo, Novartis, Pfizer und Roche und hat Vortragshonorare von Amgen, Celgene, Daiichi Sankyo, Roche, Novartis und Pfizer erhalten. M.T . war Mitglied von Beratungsgremien für AstraZeneca, Lilly, MSD, Novartis, Pfizer, Genomic Health und Roche und hat Vortragshonorare von MSD, Lilly, Roche, Novartis, Pfizer, Genomic Health und AstraZeneca erhalten. M. W. war Mitglied von Beratungsgremien für AstraZeneca, Lilly, MSD, Novartis, Pfizer und Roche. J. H. gibt an, Referentenvermittlungshonorare von Celgene, Novartis und Roche zu erhalten und ist Berater/Mitglied von Beratungsgremien für Amgen, Celgene, Novartis und Roche.

A German working group of leading breast cancer experts have discussed the votes at the International St. Gallen Consensus Conference in Vienna for the treatment of primary breast cancer with regard to the German AGO (Ar-beitsgemeinschaft Gynäkologische Onkologie) recommendations for clinical practice in Germany. Three of the German breast cancer experts were also members of this year's St. Gallen panel. Comparing the St. Gallen recommendations with the annually updated treatment recommendations of the Gynecological Oncology Working Group (AGO Mamma 2019) and the German S3 Guideline is useful, because the recommendations of the St. Gallen panel are based on expert opinions of different countries and disciplines. The focus of this article is on systemic therapy. The motto of this year's 16th St. Gallen Consensus Conference was "Estimating the magnitude of clinical benefit." The rationale behind this motto is that, for every treatment decision, a benefit-risk assessment must be taken into consideration for each patient., Competing Interests: Prof. Diana Lüftner received honoraria from AstraZeneca, Celgene, Pfizer, Novartis, Amgen, Roche, Loreal, Teva, Tesaro, and Eli Lilly. Dr. med. Ingo Bauerfeind has no conflict of interest. Prof. Michael Braun received honoraria from AstraZeneca, Celgene, Daiichi Sankyo, Genomic Health, GSK, Eisai, Genomic Health, GlaxoSmithKline, Medac, Novartis, Pfizer, Puma Biotechnology, Roche, and Teva. Prof. Sara Y. Brucker received honoraria from Novartis, Pfizer, AstraZeneca, and Roche and research funding from Genomic Health. Prof. Peter A. Fasching received funding from Novartis, Cepheid, and BioNTech and honoraria from Novartis, Roche, Pfizer, Celgene, Daiichi-Sankyo, Teva, AstraZeneca, Merck Sharp & Dohme, Myelo Therapeutics, MacroGenics, Esai, and Puma. Prof. Ricardo Felberbaum, Dr. med. Friederike Hagemann, and Renate Haidinger have no conflict of interest. Prof. Nadia Harbeck received honoraria from Agendia, Amgen, Celgene, Genomic Health, Lilly, MSD, Nanostring, Novartis, Pfizer, Roche, and Sandoz. Prof. Arnd Hönig received honoraria from Amgen, Astra Zeneca, Celgene, MSD, Pfizer, Roche, and Novartis, research funding from Roche and Genentech, and travel grants from Roche, AstraZeneca, Daiichi Sankyo, and Pfizer. Prof. Jens Huober received honoraria from Celgene, Roche, Novartis, Hexal, Pfizer, AstraZeneca, Lilly, Amgen, Eisai, and MSD, research funding from Celgene and Novartis, and travel grants from Roche, Novartis, Celgene Pfizer, und Daiichi-Sankyo. Prof. Christian Jackisch received honoraria from Celgene, Novartis, Pfizer, AstraZeneca, and Roche and research funding from Genomic Health. Prof. Thorsten Kühn has no conflict of interest. PD Dr. Hans-Christian Kolberg received honoraria from Pfizer, Novartis, Roche, Genomic Health, Amgen, AstraZeneca, Riemser, Carl Zeiss Meditec, Teva, Theraclion, Janssen-Cilag, GSK, and LIV Pharma and honoraria for consultancy activity from Pfizer, Novartis, SurgVision, Carl Zeiss Meditec, Amgen, and Onkowissen and holds shares in Theraclion SA and Phaon Scientific GmbH; he received travel grants from Carl Zeiss Meditec, LIV Pharma, Novartis, Amgen, Pfizer, and Daiichi Sankyo. Prof. Cornelia Kolberg-Liedtke received honoraria from Roche, AstraZeneca, Celgene, Novartis, Pfizer, Lilly, Hexal, Amgen, Eisai, and SonoScape, honoraria for consultancy from Phaon Scientific, Novartis, Pfizer, and Celgene, research funding from Roche, Novartis, and Pfizer, and travel grants from Novartis and Roche. Prof. Nicolai Maass received honoraria from Amgen, AstraZeneca, Celgene, Lilly, MSD, Pfizer, Roche, Novartis, and Daiichi Sankyo. Prof. Toralf Reimer received honoraria from Novartis, Pfizer, Lilly, Celgene, and AstraZeneca. Prof. Andreas Schneeweiss received honoraria from Celgene, Roche, Pfizer, AstraZeneca, Novartis, MSD, Tesaro, and Lilly, research support from Celgene, Roche, AbbVie, and Molecular Partners, and travel grants from Celgene, Roche, and Pfizer. Eva Schumacher-Wulf has no conflict of interest. Prof. Florian Schütz received honoraria for lectures and consultations from Amgen, AstraZeneca, ClinSol, MSD, Novartis, Pfizer, Riemser, and Roche and travel grants from AstraZeneca, Pfizer, and Roche. PD Dr. Marc Thill received honoraria from Amgen, AstraZeneca, Aurikamed, Biom'Up, Celgene, Daiichi Sankyo, Eisai, Genomic Health, Hexal, Lilly, MCI, Medtronic, MSD, Myriad, Neodynamics, Norgine, Novartis, OnkoLive, OmniaMed, pfm Medical, Pfizer, Roche, Tesaro, Teva, RTI Surgical, Onkowissen, Sysmex, and Clovis and research funding from Genomic Health. Prof. Michael Untch received honoraria from the employer (for Ad Board participation, lectures) and travel grants from Amgen, Astra Zeneca, BMS, Celgene, Daiichi Sankyo, Eisai, Janssen Cilag, Johnsen and Johnsen, Lilly Deutschland, Lilly International, MSD Merck, Mundipharma, Myriad Genetics, Odonate, Pfizer, PUMA Biotechnology, Riemser, Roche, Sanofi Aventis, Sividon Diagnostics, and Teva Pharmaceutical Industries Ltd. Dr. med. Rachel Wuerstlein received honoraria from Agendia, Amgen, AstraZeneca, Boehringer Ingelheim, Carl Zeiss, Celgene, Daiichi-Sankyo, Esai, Genomic Health, GSK, Lilly, MSD, Mundipharma, Nanostring, Novartis, Odonate, Paxman, Palleos, Pfizer, Pierre Fabre, Puma Biotechnology, Riemser, Roche, Sandoz/Hexal, Seattle Genetics, Tesaro Bio, and Teva. Prof. Christoph Thomssen received honoraria from AstraZeneca, Celgene, Genomic Health, Novartis, NanoString, Pfizer, and Roche and research funding from NanoString., (Copyright © 2019 by S. Karger AG, Basel.)

Competing Interests: The conflict of interest statements of all authors with conflicts of interest can be found in the supplementary material (see www.karger.com/doi/10.1159/000501000).

Every year the Breast Committee of the Arbeitsgemeinschaft Gynäkologische Onkologie (German Gynecological Oncology Group, AGO) , a group of gynecological oncologists specialized in breast cancer and interdisciplinary members specialized in pathology, radiologic diagnostics, medical oncology, and radiation oncology, prepares and updates evidence-based recommendations for the diagnosis and treatment of patients with early and metastatic breast cancer. Every update is performed according to a documented rule-fixed algorithm, by thoroughly reviewing and scoring the recent publications for their scientific validity and clinical relevance. This current publication presents the 2019 update on the recommendations for metastatic breast cancer., Competing Interests: The conflict of interest statements of all authors with conflicts of interest can be found in the supplementary material (see www.karger.com/doi/10.1159/000500999).

Purpose: The aim of the current work was to clarify whether a preoperative lymphoscintigraphy (LSG) enhances staging accuracy of sentinel lymph node biopsy (SLNB)., Patients and Methods: In a prospective, multicenter, randomized phase III trial, patients with cN0 early breast cancer or extensive/high-grade ductal carcinoma in situ planned for standard radioactive-labeled colloid LSG with subsequent SLNB were randomly assigned 1:1 to receive SLNB either with knowledge of the LSG findings or without. As the false-negative rate of SLNB correlates with the number of resected sentinel lymph nodes (SLNs), our primary end point was the mean number of histologically detected SLNs per patient. One thousand one hundred two evaluable patients were necessary to demonstrate noninferiority of SLNB without LSG. Stratified one-sided 95% CI for the difference (without LSG - with LSG) in the mean number of histologically detected SLNs had to be greater than -0.27 (10% noninferiority margin). Stratification was performed according to tumor focality and trial site. Additional predefined secondary end points (rates of node-positive patients and of completion axillary lymph node dissection) were analyzed to rule out differences in the reliable detection of nodal metastases., Results: Between May 2014 and October 2015, 1,198 patients were randomly assigned in 23 German and Swiss breast centers. Modified intention-to-treat analysis (n = 1,163) showed a mean number of histologically detected SLNs of 2.21 with LSG and 2.26 without LSG (difference 0.05; stratified 95% CI, -0.18 to infinity), thus establishing noninferiority of omitting preoperative LSG. Secondary end points displayed no statistically significant differences., Conclusion: We show that SLNB is equally effective irrespective of the surgeon's knowledge of preoperative LSG results. SLNB without LSG will speed up the preoperative workflow and reduce cost.

This year's annual AWOgyn meeting focused on studies of reconstructive breast surgery. As the majority of breast reconstructions are implant-based, most studies also focused on implant-based reconstruction. Since 2011, the guidelines have recommended using interposed mesh materials as support. The basic idea behind every type of material is to provide coverage and stabilization for the implant by constructing an "internal bra" which will create the appropriate implant shape and maintain the position, stability and flexibility of the implant. The Working Group for Reconstructive Surgery in Oncology-Gynecology (AWOgyn) has undertaken to analyze different materials with regard to indications, success rates and side effects as documented in registers, clinical assessments and study protocols. This has increased application safety and is expected to improve it even further in future. Prospective studies are being carried out to investigate issues such as the optimal material, optimal implant site and best cosmetic results. The first results for porcine and human acellular matrices and for partially resorbable titanium-coated synthetic polypropylene meshes are now available. In 2019, the AWOgyn working group will be launching further studies to evaluate a perforated acellular dermal matrix (Fortiva ® ), a titanium-coated implant pocket (TiLOOP ® Bra Pocket) and a fully resorbable synthetic mesh (TIGR ® mesh).

Purpose: The WSG-PRIMe Study prospectively evaluated the impact of the 70-gene signature MammaPrint® (MP) and the 80-gene molecular subtyping assay BluePrint® on clinical therapy decisions in luminal early breast cancer., Methods: 452 hormone receptor (HR)-positive and HER2-negative patients were recruited (N0, N1). Physicians provided initial therapy recommendations based on clinicopathological factors. After prospective risk classification by MammaPrint/BluePrint was revealed, post-test treatment recommendations and actual treatment were recorded. Decisional Conflict and anxiety were measured by questionnaires., Results: Post-test switch (in chemotherapy (CT) recommendation) occurred in 29.1% of cases. Overall, physician adherence to MP risk assessment was 92.3% for low-risk and 94.3% for high-risk MP scores. Adherence was remarkably high in "discordant" groups: 74.7% of physicians initially recommending CT switched to CT omission following low-risk MP scores; conversely, 88.9% of physicians initially recommending CT omission switched to CT recommendations following high-risk MP scores. Most patients (99.2%) recommended to forgo CT post-test and 21.3% of patients with post-test CT recommendations did not undergo CT; among MP low-risk patients with pre-test and post-test CT recommendations, 40% did not actually undergo CT. Luminal subtype assessment by BluePrint was discordant with IHC assessment in 34% of patients. Patients' State Anxiety scores improved significantly overall, particularly in MP low-risk patients. Trait Anxiety scores increased slightly in MP high risk and decreased slightly in MP low-risk patients., Conclusions: MammaPrint and BluePrint test results strongly impacted physicians' therapy decisions in luminal EBC with up to three involved lymph nodes. The high adherence to genetically determined risk assessment represents a key prerequisite for achieving a personalized cost-effective approach to disease management of early breast cancer.

The results of the international St. Gallen Consensus Conference for the treatment of patients with primary breast cancer were discussed this year by a working group of leading breast cancer experts in view of the therapy recommendations for everyday clinical practice in Germany. Three of the breast cancer experts are also members of this year's St. Gallen panel. The comparison of the St. Gallen recommendations with the annually updated treatment recommendations of the AGO 2019 as well as the S3 guideline is useful, since the recommendations of the St. Gallen panel represent the opinions of experts from various countries and disciplines. The recommendations of the S3 guideline and AGO are based on evidence-based research of the literature. This year's 16th St. Gallen conference featured the motto "Magnitude of clinical benefit". In addition to the evidence-based data, each therapeutic decision must also undergo a benefit/risk assessment of the patient's individual situation and be discussed with the patient.

The E-VITA study evaluated the efficacy and tolerability of two schedules of eribulin and lapatinib in patients with trastuzumab-pretreated HER-2-positive metastatic breast cancer. This multicenter, open-label phase II trial, randomly assigned patients with trastuzumab-pretreated HER-2-positive metastatic breast cancer to lapatinib 1000 mg daily with eribulin 1.23 mg/m (equivalent to 1.4 mg/m eribulin mesylate) days 1+8 every 21 days (split-dose arm) or eribulin 1.76 mg/m (equivalent to 2.0 mg/m eribulin mesylate) day 1 every 21 days (3-weekly arm). Time to progression and tolerability were defined as primary end points; no sample size calculation for formal comparison of efficacy data has been performed. Secondary end points included objective response rate, clinical benefit rate, and overall survival. Overall, 43 patients of a planned number of 80 patients were recruited. At a median follow-up of 28.7 months, the median time to progression was 8.1 months [95% confidence interval (CI): 4.8-9.4] in the split-dose arm and 6.5 months (95% CI: 4.6-13.4) in the 3-weekly arm. Objective response rate was 52.4% (95% CI: 31.0-73.7) in the split-dose arm and 45.0% (95% CI: 23.2-66.8) in the 3-weekly arm, and clinical benefit rate was 71.4% (95% CI: 52.1-90.8) and 75.0% (95% CI: 56.0-94.0), respectively. Overall survival was also similar in both arms. The most frequent grade 3-4 adverse events were neutropenia (58.5%) and leukopenia (39.0%). The combination of eribulin and lapatinib showed an acceptable safety profile with less toxicity observed in the eribulin 1.23 mg/m day 1+8 group. This might be an alternative regimen when other treatment options are exhausted. Therefore, further clinical studies are warranted.

As originator biologic medicines lose patent protection, some biopharmaceutical companies are focusing on developing similar versions of these costly and complex therapies with a goal of providing more affordable treatment options. Many of these molecules, known as biosimilars, are now approved worldwide and several more are expected to be introduced in the near future. As more biosimilars become available, it is important for clinicians to become familiar with this new category of products and understand how biosimilars are developed, how their development differs from that of originator biologics and how they differ from generics. This review aims to provide the practicing clinician with the knowledge needed to understand biosimilars, along with some guidance on their use in treating oncologic diseases.

In the last decade, cancer therapies have increasingly taken the form of combination treatments in which biologic agents play a crucial role. In breast cancer, the treatment strategy is adjusted to intrinsic subtypes such as human epidermal growth factor receptor-2(HER2)-positive. With the introduction of trastuzumab, a monoclonal antibody against HER2, survival has significantly improved in early and metastatic breast cancer. Trastuzumab's patent has now expired and biosimilars are moving into the market. Several clinical trials have led to the approval of 5 different biosimilar trastuzumabs. Results proved similarity between the proposed biosimilar and the reference product without significant differences in efficacy and safety, although follow-up has been short. However, the shorter drug development process with its goal of showing similarity rather than patient benefit uses surrogate endpoints such as pathologic complete response and overall response rate, not survival endpoints in terms of the 'gold standarD' in evaluating cancer therapies. The aim of this article is to give insight into how to plan and perform a clinical trial to prove equivalence between a biosimilar trastuzumab and its reference product and to elucidate the setup and outcome of published clinical trials.

Cyclin-dependent kinase (CDK) 4/6 inhibitors have shown great results in numerous clinical trials and have improved the clinical outcome for patients with hormone-receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer significantly. To date, three CDK4/6 inhibitors are approved by the US Food and Drug Administration (FDA): palbociclib, ribociclib and abemaciclib; the first two compounds are aproved by the European Medicines Agency (EMA) as well. In combination with endocrine therapy, all of them led to significantly improved progression-free survival compared with endocrine therapy alone. The aim of this article is to give an overview of the efficacy data and to describe the CDK4/6 inhibitor-based treatment-associated adverse events, including hematological and nonhematological adverse events. In addition, it describes the corrrect approach to patient monitoring and adverse event mangement and summarizes the current recommendations for dose reductions and dose interruptions regarding the key adverse events, such as neutropenia, diarrhea, QTc prolongation and hepatobiliary toxicity. Accurate patient monitoring and management of the side effects is crucial, as several clinical trials in early breast cancer are in progress and may lead to an additional approval in the neo-/adjuvant setting., Competing Interests: Conflict of interest: Marc Thill has received speaker honoraria by Pfizer and Novartis, consultant honoraria by Pfizer, Novartis and Lilly, travel reimbursement by Pfizer, Novartis and Lilly. Marcus Schmidt has received speaker honoraria by Pfizer and Novartis, consultant honoraria by Pfizer and Novartis, and travel reimbursement by Pfizer and Novartis.

Background: Neoadjuvant chemotherapy (NACT) is a standard approach of the multidisciplinary treatment of breast cancer. Depending on the biological subtype a pathological complete response in the breast (bpCR) can be achieved in up to 60% of the patients. However, only limited accuracy can be reached when using imaging for prediction of bpCR prior to surgery. Due to this diagnostic uncertainty, surgery after NACT is considered to be obligatory for all patients in order to either completely remove residual disease or to diagnose a bpCR histologically. The purpose of this trial is to evaluate the accuracy of a vacuum-assisted biopsy (VAB) to diagnose a bpCR after NACT prior to surgery., Methods: This study is a multicenter, confirmative, one-armed, intra-individually-controlled, open, diagnostic trial. The study will take place at 21 trial sites in Germany. Six hundred female patients with breast cancer after completed NACT showing at least a partial response to NACT treatment will be enrolled. A vacuum-assisted biopsy (VAB) guided either by ultrasound or mammography will be performed followed by histopathological evaluation of the VAB specimen before standard, guideline-adherent breast surgery. The study is designed to prove that the false negative rate of the VAB is below 10%., Discussion: As a bpCR is becoming a more frequent result after NACT, the question arises whether breast surgery is therapeutically necessary in such cases. To study this subject further, it will be crucial to develop a reliable test to diagnose a bpCR without surgery. During the study we anticipate possible problems in patient recruitment as the VAB intervention does not provide participating patients with any personal benefit. Hence, a proficient informed consent discussion with the patient and a detailed explanation of the study aim will be crucial for patient recruitment. Another critical issue is the histopathological VAB evaluation of a non-tumorous specimen as this may have been taken either from the former tumor region (bpCR) or outside of the (former) tumor region (non-representative VAB, sampling error)., Trial Registration: The trial has been registered at clinicaltrials.gov with the identifier NCT02948764 on October 28, 2016 and at the German Clinical Trials Register ( DRKS00011761 ) on February 20, 2017. The date of enrolment of the first participant to the trial was on March 8, 2017.

This article is the result of a round-table discussion organised by ESMO Open in Vienna in December 2017. Its purpose is to discuss the background and advances in the evidence regarding cyclin-dependent kinase 4/6 inhibitors (palbociclib, ribociclib and abemaciclib) in the treatment of metastatic and early-stage breast cancer and to explore what the key open research questions are and next steps should be., Competing Interests: Competing interests: MP: research support from Boehringer-Ingelheim, GlaxoSmithKline, Merck Sharp & Dohme and Roche and honoraria for lectures, consultation or advisory board participation from Bristol-Myers Squibb, Novartis, Gerson Lehrman Group (GLG), CMC Contrast, GlaxoSmithKline, Mundipharma, Roche, AstraZeneca and AbbVie. MT: advisory role at: Amgen, AstraZeneca, Celgene, Eisai, Genomic Health, Lilly, Neodynamics, Novartis, Pfizer, pfm Medical, Roche, RTI Surgical, SurgicEye, Tesaro, Teva. Speaker engagements and travel support: Amgen, AstraZeneca, Boehringer Ingelheim, Celgene, Eisai, Genomic Health, Medtronic, Myriad, Novartis, Pfizer, pfm Medical, Roche, RTI Surgical, Teva. Manuscript fees: Roche, Celgene. Trial funding: Genomic Health. RB: advisory role: Eli-Lilly, Novartis, Pfizer; Lecture honoraria: Eli-Lilly, Novartis, Pfizer; research support: Novartis; Travel support: Pfizer. TR: advisory role for: Lilly, Roche, Novartis, Pfizer, AstraZeneca; Travel support: Roche, Amgen. EdA: honoraria and advisory board: Roche/GNE; travel grants: Roche/GNE and GSK/Novartis; research grant: Roche/GNE. CCZ: Honoraria from Ariad, Novartis, Boehringer-Ingelheim, Roche and AstraZeneca.

Importance: Studies of neoadjuvant chemotherapy regimens using anthracyclines followed by taxanes have reported a doubling of pathological complete remission (pCR) rates compared with anthracycline-based regimens alone. A reverse sequence did not reduce activity. Nab-paclitaxel is an albumin-bound nanoparticle of paclitaxel that allows for safe infusion without premedication, and its use led to a significantly higher rate of pCR in the GeparSepto trial., Objective: To determine whether nab-paclitaxel improves the outcomes of early and locally advanced human epidermal growth factor receptor 2 (ERBB2/HER2)-negative breast cancer compared with paclitaxel when delivered in a neoadjuvant setting., Design, Setting, and Participants: In this multicenter, open-label study, in collaboration with Grupo Español de Investigación en Cáncer de Mama (GEICAM) and Breast Cancer Research Center-Western Australia (BCRC-WA), patients with newly diagnosed and centrally confirmed ERBB2/HER2-negative breast cancer were recruited. Participants were randomly allocated to paclitaxel, 90 mg/m2 (349 patients), or nab-paclitaxel, 125 mg/m2 (346 patients). The 2 drugs were given on weeks 1, 2, and 3 followed by 1 week of rest for 4 cycles before 4 cycles of an anthracycline regimen per investigator choice., Main Outcomes and Measures: The primary end point was the rate of pCR, defined as absence of invasive cells in the breast and axillary nodes (ie, ypT0/is ypN0) at the time of surgery. A secondary end point was to assess tolerability and safety of the 2 regimens., Results: From May 2013 to March 2015, 814 patients were registered to the study; 695 patients met central confirmation eligibility and were randomly allocated to receive either paclitaxel (349), or nab-paclitaxel (346) (median age, 50 years; range, 25-79 years). The intention-to-treat analysis of the primary end point pCR revealed that the improved pCR rate after nab-paclitaxel (22.5%) was not statistically significant compared with paclitaxel (18.6%; odds ratio [OR], 0.77; 95% CI, 0.52-1.13; P = .19). Overall, 38 of 335 patients (11.3%) 11.3% of patients had at least 1 serious adverse event in the paclitaxel arm and 54 of 337 patient (16.0%) in the nab-paclitaxel arm. Peripheral neuropathy of grade 3 or higher occurred in 6 of 335 patients (1.8%) and in 15 of 337 (4.5%), respectively., Conclusions and Relevance: The improved rate of pCR after nab-paclitaxel was not statistically significant. The multivariate analysis revealed that tumor subtype (triple-negative vs luminal B-like) was the most significant factor (OR, 4.85; 95% CI, 3.28-7.18) influencing treatment outcome., Trial Registration: clinicaltrials.gov Identifier: NCT01822314.

Background: Vitamin D is known for its anticancer potential. Prostaglandin E 2 (PGE 2 ) is a proliferative and inflammation-activating agent. The production of PGE 2 is dependent on the activity of cyclooxygenase-2 (COX2). A link between vitamin D and PGE 2 metabolism was shown recently., Materials and Methods: In MDA-MB-231 and MCF-7 breast cancer cell lines, we investigated the influence of calcitriol and the COX2 inhibitor celecoxib on cell growth via the MTT test, as well as on the protein and mRNA expression of COX2 using western blot and quantitative real-time polymerase chain reaction (qRT-PCR)., Results: The proliferation of MCF-7 and MDA-MB-231 was inhibited by both calcitriol and the COX2 inhibitor celecoxib and even more strongly by their combination. Moreover, calcitriol inhibited COX2 protein expression in MDA-MB-231 cells, as well as COX2 mRNA expression in both cell lines., Conclusion: The combination of calcitriol and celecoxib demonstrated a synergistic growth-inhibitory effect in breast cancer cell lines., (Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

The likelihood of pathological complete remission (pCR) of breast cancer following neoadjuvant chemotherapy (NACT) is increasing; most of all in the triple negative and HER2 positive tumour subgroups. The question thus arises whether or not breast surgery is necessary when there is complete remission after NACT, and whether it provides any improvement of the oncological treatment result when tumour is no longer detectable. Avoiding surgery and possibly even radiotherapy would only be conceivable on the basis of a reliable diagnosis of pCR without operating. Current imaging does not achieve the necessary sensitivity and specificity to assure the diagnosis of pathological complete remission. Further studies are therefore required to determine which methods are best able to evaluate tumour response to NACT. Studies on image-guided, minimally invasive biopsies after NACT have delivered first promising results towards diagnosing pCR before surgery and could provide the basis for further studies on the possibility of avoiding surgery in this specific patient collective.

Claudin-1 is a tight junction protein that has been demonstrated to be involved in tumorigenesis and tumor progression in various types of solid tumors. In the present study, the protein expression of claudin-1 in squamous cervical cancer tissues obtained from 106 patients was analyzed by immunohistochemistry. In addition, the grade of claudin-1 expression was analyzed for associations with certain clinicopathological parameters. A significant overexpression of claudin-1 was detected in the tumor cells, when compared with that in the peritumoral stroma. There was no significant association between claudin-1 expression and FIGO stage, tumor size, grading or the appearance of distant metastases. Cervical cancer patients scoring positive for claudin-1 protein expression tended to exhibit more lymph node metastasis (28.3%), compared with claudin-1-negative patients (7.1%). Regarding overall survival, the results of the present study suggest a better prognosis for claudin-1-negative patients. In order to elucidate whether claudin-1 overexpression has a significant prognostic impact on squamous cervical cancer, further studies are required.

Background: Except for meeting the individual palliative need, the benefit of breast surgery in primary metastatic breast cancer (PMBC), also known as de novo metastatic breast cancer, on long-term outcomes remains controversial. Twenty-four hundred and one patients with metastatic breast cancer, enrolled between 2000 and 2011 in two prospective non-interventional studies on targeted therapy, were screened with respect to this question., Methods: One study investigated trastuzumab therapy for human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer in addition to mainly first-line chemotherapy. The other observed bevacizumab added to chemotherapy as first-line treatment for mostly HER2-negative disease., Results: Five-hundred and seventy (24%) patients presented with PMBC, and valid information on resection of the primary tumour was available for 568 women. Out of these, 426 (75%) underwent local resection. The latter group was characterised by less overall metastatic burden and a lower proportion of T4 tumours. No major differences were observed with respect to age, hormone receptor and HER2 status, visceral disease and performance status. Numerically, the surgery group showed a slightly favourable progression-free survival (PFS, medians: 13.6 versus 11.8 months; P = 0.18) and overall survival (OS, 34.1 versus 31.7; P = 0.23). However, in multivariable analysis, including all other univariably significant parameters, no trend for better outcome after surgery remained detectable, neither for PFS (hazard ratio 0.99; P = 0.92) nor for OS (0.95; P = 0.71)., Conclusions: Our findings suggest no major survival benefit for local resection in the overall PMBC population treated with modern targeted therapies. However, further analyses are warranted to define specific risk groups, which may benefit from surgical removal of the primary., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

The St. Gallen International Consensus Conference on the treatment of patients with primary breast cancer has been held regularly (every second year in the last six years) for more than 30 years. This year, the findings of the International St. Gallen Consensus Panel and their implications for clinical practice were again discussed by a German working group of leading breast cancer specialists. Five of the breast cancer specialists from Germany were also members of this year's St. Gallen panel. A comparison between the St. Gallen recommendations and the annually updated treatment guidelines of the Gynecologic Oncology Group (AGO 2017) and the S3-guideline agreed upon in 2017 is useful. The recommendations of the St. Gallen panel represent an international cross-section of opinions of experts from different countries and different disciplines, while the S3-guideline and AGO guidelines are evidence-based. The motto of this year's 15th St. Gallen Conference was "Escalating and De-Escalating". The rationale behind this concept was to promote more individualized treatment and thereby reduce overtreatment as well as undertreatment.

Cyclooxygenase-2 (COX-2) is associated with carcinogenesis and tumor progression. The current study analyzed the effect of COX-2 expression in patients with invasive squamous cervical cancer. Tissue samples from 123 cervical cancer patients were collected for a retrospective analysis using immunohistochemistry (IHC) with an antibody against COX-2. The clinical and survival data of the patients were analyzed. Positive staining for COX-2 (defined as an immunoreactivity score of ≥4) was detected in 28 patients (23%), with significantly higher percentages of staining in tumor cells compared with peritumoral stroma cells (P<0.001). COX-2 expression was significantly associated with lymphovascular space invasion (LVSI; P=0.017). The association of COX-2 expression with LVSI suggests a possible effect of COX-2 on tumor progression in cervical cancer. Further studies including larger patient collectives are required in order to perform analyses of clinical subgroups and patient survival.

Background: Therapists and administrative bodies consider a pathological complete remission as an independent and relevant endpoint in evaluations of the clinical utility of neoadjuvant therapy for early breast cancer. The present study aims to investigate which treatment outcomes of a neoadjuvant therapy are considered by the patients themselves to be relevant. Materials and Methods: With the help of analytic hierarchy process (AHP) methods patient preferences about the treatment targets of neoadjuvant therapy were assessed quantitatively. All participants had undergone a neoadjuvant therapy in the form of chemotherapy and, in HER2-positive cases, as a targeted antibody therapy against HER2 for the primary diagnosis of early breast cancer 12-36 months prior to the interview. The criteria for the hierarchy model were identified in an earlier qualitative survey. The patient interviews were conducted by 4 experienced female interviewers. Results: Forty-one patients participated in the quantitative survey, of these 15 (36.6 %) had suffered from HER2-positive disease. The achievement of pCR was the most important therapeutic target for the patients, even before disease-free survival, overall survival and the option for breast-preserving operation. Avoidance of side effects was considered to be the least important. In a comparison of the side effects the patients judged fatigue to be most important before nausea and loss of hair. Conclusion: For the patients the achievement of a pathological complete remission is considered to be an independent, relevant and highly desired target of neoadjuvant therapy.

The Advanced Breast Cancer Third International Consensus Conference on the diagnosis and treatment of advanced breast cancer took place in Lisbon, Portugal, on November 5-7, 2015. This year's conference (ABC3) was focused on the treatment of metastatic breast cancer (stage IV), as it was 4 years ago at the first consensus meeting (ABC1). A matter of particular interest was the patients' perspective. Thus, patient-relevant issues were addressed by the consensus discussions, such as those on treatment goals, quality of life, care of long-term survivors ('survivorship issues'), and coping with disease-related symptoms and the side effects of treatment. Further important issues on the agenda were the use of standardized instruments for the assessment of individual treatment success ('patient-reported outcome measures') and the evaluation of the benefit of novel drugs (e.g. the European Society for Medical Oncology (ESMO) Magnitude of Clinical Benefit Scale). Diagnosis and treatment of inoperable locally advanced breast cancer had already been discussed 2 years earlier at the ABC2 Consensus and were not dealt with in the framework of this year's ABC3 Consensus. With regard to country-specific peculiarities, which unavoidably found their way into the ABC Consensus, a working group of German breast cancer experts commented on the voting results of the ABC panelists. As for the past consensus, the group specially considered the German guidelines for the diagnosis and treatment of breast cancer (AGO (Gyneco-Oncology Working Group), S3, DGHO (German Society of Hematology and Medical Oncology)) in order to adapt the ABC3 consensus for everyday therapy in Germany.

The Third International Consensus Conference for Advanced Breast Cancer ABC3 on the diagnosis and treatment of advanced breast cancer was held in Lisbon from 5 to 7 November 2015. This year the focus was the treatment of metastatic breast cancer (stage IV) - including the patient perspectives. Important topics were questions relating to quality of life, the care for long-term survivors as well as the management of disease-related symptoms and treatment-based side effects. The use of standardised tools to assess individual treatment success and the benefits of new substances were important points for discussion. The diagnosis and treatment of inoperable locally advanced breast cancer were discussed two years ago during the ABC2 consensus 1. A working group of German breast cancer experts commented on the results of the ABC panellists, paying particular attention to the German guidelines (AGO, S3, DGHO) on the diagnosis and treatment of breast cancer 2, 3, 4, 5 in Germany.

Categorization, risk assessment, and treatment of breast cancer have been revolutionized by the original description of the human epidermal growth factor receptor 2 (HER2), first as a prognostic marker and then as a therapeutic target. The HER2-positive subtype of breast cancer represents less than approximately 20% of the incident breast cancers. Nevertheless, many lessons can be learned from the development of anti-HER2 therapies in early-stage disease. This review will comment on the key studies in both the (neo)adjuvant and metastatic settings and discusses some of the controversies that still remain today both in clinical care and as research questions., (© 2016 S. Karger GmbH, Freiburg.)

Purpose: Official guideline published and coordinated by the German Society of Gynecology and Obstetrics (DGGG). Positioning injuries after lengthy gynecological procedures are rare, but the associated complications can be potentially serious for patients. Moreover, such injuries often lead to claims of malpractice and negligence requiring detailed medical investigation. To date, there are no binding evidence-based recommendations for the prevention of such injuries. Methods: This S1-guideline is the work of an interdisciplinary group of experts from a range of different professions who were commissioned by DGGG to carry out a systematic literature search of positioning injuries. Members of the participating scientific societies develop a consensus in an informal procedure. Afterwards the directorate of the scientific society approves the consensus. The recommendations cover.

Trastuzumab is a highly successful monoclonal antibody (mAb) that has been used primarily for the treatment of HER2-positive breast cancer. Because of its success and its impending patent expiry in Europe in 2014, a number of copy versions of trastuzumab have been developed and are currently undergoing a comparability exercise for marketing authorization. Although biosimilar products have been approved in Europe since 2006, including two biosimilar mAbs of infliximab approved in 2013, the use of mAbs such as trastuzumab in the cancer setting has raised a number of new concerns. The requirements for the approval of biosimilar mAbs published by the EMA will be discussed and examined in the context of trastuzumab biosimilars to highlight potential controversies.

Background: More than 50% of patients with advanced breast cancer develop bone metastases that may lead to multiple complications such as pathological fractures, bone pain or hypercalcaemia. The standard treatment, besides endocrine, targeted-therapy or chemotherapy, is the use of bisphosphonates. However, one of their main adverse side-effects is bisphosphonate-induced nephrotoxicity. The mechanism by which the latter occurs is not well-understood, although emerging evidence suggests that the effect of bisphosphonates on the kidney may differ between agents., Patients and Methods: The aim of this evaluation was to compare the renal toxicity of 6 mg ibandronate i.v. versus 4 mg zoledronic acid i.v. over a period of six months in women with breast cancer and bone metastases. A prospective randomized trial was carried out to examine specific kidney and other parameters (α1- and β2-microglobulin, albumin, α2-macroglobulin, IgG and C-reactive protein (CRP) generated from spontaneous urine samples from 17 patients of each group., Results: We were unable to find any significant difference between the two treatment groups with regard to renal toxicity. All patients, independently of the applied bisphosphonate, experienced only temporary renal dysfunction without any evidence of irreversible damage in terms of acute nephrotoxicity during the study period. α1-Microglobulin, a marker for proximal tubular damage, in particular, was not differently elevated in either group., Conclusion: Both applied bisphosphonates were found to be well-tolerated and safe with regard to renal toxicity during a six-month treatment period in patients with otherwise healthy kidneys having advanced breast cancer and bone metastases., (Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)

Background: Vitamin D is known for its anti-cancerogenous potential. Prostaglandin E2 (PGE2) is a proliferation and inflammation activating agent. The production of PGE2 is dependent on the activity of cyclooxygenase-2 (COX-2). A link between vitamin D and PGE2 metabolism was recently shown., Materials and Methods: In MDA-MB-231 and MCF-7 breast cancer cell lines we investigated the influence of calcitriol and the COX-2 inhibitor celecoxib regarding cell growth via MTT test, as well as on the protein and mRNA expression of COX-2 using western blot and qRT-PCR., Results: The proliferation of MCF-7 and MDA-MB-231 was inhibited by both calcitriol and the COX-2 inhibitor celecoxib and even stronger by their combination. Moreover, calcitriol inhibited the COX-2 protein expression in MDA-MB-231, as well as the COX-2 mRNA expression in both cell lines., Conclusion: The combination of calcitriol and celecoxib demonstrated a cooperative growth-inhibiting effect in breast cancer cell lines., (Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)

Background: Vitamin D exhibits multiple anti-proliferative and pro-differentiating actions. Prostaglandin-(PG)E2 is a tumor-promoting tissue hormone anabolized by cyclooxygenase-2 (COX-2). Recently, a link between the PG and vitamin D metabolism was reported., Materials and Methods: The influence of calcitriol and celecoxib on the proliferation of ovarian cancer cell lines was measured and the impact of calcitriol on the protein and mRNA expression of COX-2 was quantified by western blot and qRT-PCR, respectively., Results: After COX-2 induction with interleukin (IL)-1β, 10 μM celecoxib did not significantly inhibit the proliferation of OVCAR-3 cells, whereas calcitriol showed such an effect; however, the combination of the two substances had an additive influence. After induction by IL-1β, calcitriol inhibited the COX-2 protein, as well as its mRNA expression significantly in OVCAR-3 and SKOV-3 cells., Conclusion: These data suggest a correlation between PG and vitamin D metabolism in their anti-tumorigenic activity in ovarian carcinomas., (Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)

Purpose: Chemotherapy with anthracyclines, taxanes, or alkylating agents often causes cutaneous side effects. Nonspecific inhibition of the proliferative activity of keratinocytes has antidifferentiation effects that lead to defects in the barrier function and, thus, to dry, itchy, and irritable skin. These cutaneous symptoms reduce the quality of life of the patients considerably. Conditioning with topical application of niacinamide uses the cytoprotective and barrier stabilizing effect of vitamin B3., Patients and Methods: A multicenter randomized crossover study investigated the influence of the test preparation on the quality of life compared to standard care for 73 patients with breast cancer undergoing adjuvant or neoadjuvant cytostatic therapy. Primary target parameter was the Dermatology Life Quality Index with its respective subscales after 6 weeks of a twice-daily application of the respective preparations. Additionally, specific symptoms such as pruritus, dryness, and irritability have been assessed using visual analog scales., Results: Regarding the total score of the Dermatology Life Quality Index, no relevant differences could be observed. However, the results for the "symptoms and feelings" subscale show a significant advantage in favor of the test preparation. Significant superiority of the test preparation could also be observed in the secondary target parameters, the visual analog scales (P<0.05)., Conclusion: The results show for the first time a significant superiority of prophylactic application of niacinamide for maintaining quality of life while undergoing cytostatic treatment.

A positive margin in breast conserving surgery is associated with an increased risk of local recurrence. Failure to achieve clear margins results in re-excision procedures. Methods for intraoperative assessment of margins have been developed, such as frozen section analysis, touch preparation cytology, near-infrared fluorescence optical imaging, x-ray diffraction technology, high-frequency ultrasound, micro-CT, and radiofrequency spectroscopy. In this article, options that might become the method of choice in the future are discussed., (© 2014 Wiley Periodicals, Inc.)

Purpose: To evaluate accelerated partial breast irradiation (APBI) in patients after oncoplastic surgery for early breast cancer., Methods and Materials: A retrospective analysis of 136 breasts of 134 patients, who received breast-conserving oncoplastic surgery for low-risk breast cancer between 2002 and 2010 in the Universities of Vienna and Luebeck followed by adjuvant APBI applying total doses of pulse dose rate of 50.4 Gy or high-dose rate (HDR) of 32 Gy over 4 days. Target volume definition was performed by the use of surgical-free margin data, related to intraoperatively fixed clip positions, pre- and postoperative imaging, and palpation., Results: At the time of data acquisition, 131 of 134 patients were alive. The median follow-up time was 39 months (range, 4-106 months). After high-dose rate treatment, 3 of 89 patients showed systemic progress after a mean follow-up of 47 months (range, 19-75 months) and 2 patients had a different quadrant in-breast tumor after 27 and 35 months. One patient died 7 months after treatment of unknown causes. After pulse dose rate treatment, 1 of 45 patients had a local recurrence after 42 months and 1 patient died because of another cause after 13 months. We observed mild fibrosis in 27 breasts, telangiectasia in 6, hyperpigmentation in 14 cases, and keloid formation in 1., Conclusions: These preliminary results suggest the feasibility of multicatheter APBI after oncoplastic breast-conserving surgery in selected low-risk breast cancer patients; however, special attention to target volume definition is needed. Further prospective investigations with long follow-up are needed to define the real value of the procedure., (Copyright © 2014 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.)