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Co-observation of a gene variant with a pathogenic variant in another gene that explains the disease presentation has been designated as evidence against pathogenicity for commonly used variant classification guidelines. Multiple variant curation expert panels have specified, from consensus opinion, that this evidence type is not applicable for the classification of breast cancer predisposition gene variants. Statistical analysis of sequence data for 55,815 individuals diagnosed with breast cancer from the BRIDGES sequencing project was undertaken to formally assess the utility of co-observation data for germline variant classification. Our analysis included expected loss-of-function variants in 11 breast cancer predisposition genes and pathogenic missense variants in BRCA1, BRCA2, and TP53. We assessed whether co-observation of pathogenic variants in two different genes occurred more or less often than expected under the assumption of independence. Co-observation of pathogenic variants in each of BRCA1, BRCA2, and PALB2 with the remaining genes was less frequent than expected. This evidence for depletion remained after adjustment for age at diagnosis, study design (familial versus population-based), and country. Co-observation of a variant of uncertain significance in BRCA1, BRCA2, or PALB2 with a pathogenic variant in another breast cancer gene equated to supporting evidence against pathogenicity following criterion strength assignment based on the likelihood ratio and showed utility in reclassification of missense BRCA1 and BRCA2 variants identified in BRIDGES. Our approach has applicability for assessing the value of co-observation as a predictor of variant pathogenicity in other clinical contexts, including for gene-specific guidelines developed by ClinGen Variant Curation Expert Panels., Competing Interests: Declaration of interests P.A.F. conducts research funded by Amgen, Novartis, and Pfizer. He received Honoraria from Roche, Novartis, and Pfizer. A.R.M. received funds from AstraZeneca for contribution to sponsored quality assessments and variant interpretation of VUSs in BRCA1 and BRCA2. The funds were paid to the institution., (Copyright © 2024 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.)

Endocrine-based combination therapy with an inhibitor of the cyclin-dependent kinases 4 and 6 (CDK4/6 inhibitors) is currently the first-line therapy of choice for patients with hormone receptor-positive (HR+) and human epidermal growth factor receptor 2-negative (HER2-), locally advanced or metastatic breast cancer (mBC). The efficacy and safety of the treatment with palbociclib, the first CDK4/6 inhibitor approved for this indication, have been confirmed in large randomized controlled clinical trials (RCTs) with strictly defined patient cohorts. Since then, many relevant questions about CDK4/6 inhibition with palbociclib for mBC have been investigated in RCTs and real-world studies. Based on this evidence, palbociclib is widely used in clinical practice since many years because of its efficacy and good tolerability. The aim of this review is to summarize findings from RCTs and RWE considering clinically relevant aspects such as safety, tolerability, quality of life and efficacy with a focus on specific questions and patient characteristics. A critical discussion and review of the overall evidence for endocrine-based therapy with the CDK4/6 inhibitor palbociclib can contribute to support therapy decisions in daily clinical practice., Competing Interests: Conflict of Interest Ruckhäberle, Eugen: Honoraria or fees from: Amgen, Roche, Celgene, Gilead, Pfizer, Novartis, AstraZeneca, MSD, Teva, TESARO, Pharmamar, Pierre Fabre, Exact Sciences, Janssen-Cilag, Lilly, Clovis Oncology, Onkowissen. Travel support: Pfizer, Roche, Eisai, Pierre Fabre. Research support: Roche. Schmidt, Marcus: Personal fees from AstraZeneca, BioNTech, Daiichi Sankyo, Eisai, Exact Sciences, Gilead, Lilly, Menarini Stemline, Molecular Health, MSD, Novartis, Pantarhei Bioscience, Pfizer, Pierre Fabre, Roche, and Seagen. His institution has received research funding from AstraZeneca, BioNTech, Eisai, Genentech, German Breast Group, Novartis, Palleos, Pantarhei Bioscience, Pierre Fabre, and Seagen. In addition, he has a patent for EP 2390370 B1 and a patent for EP 2951317 B1 issued. Welt, Anja: Fees from MSD, Roche, Novartis, Pfizer, Seagen, Lilly, Menarini Stemline, Pierre Fabre, iOMEDICO, Eisai, RCC, MCI, Interplan. Harbeck, Nadia: Honoraria for lectures and/or consulting: AstraZeneca, Daiichi Sankyo, Gilead, Lilly, MSD, Novartis, Pierre Fabre, Pfizer, Roche, Seagen, Viatris, Zuelligpharma. Other: Co-Director West German Study Group (WSG). Wöckel, Achim: Amgen, AstraZeneca, Celgene, Lilly, Novartis, Pfizer, Roche, MSD, Genomic Health, Organon, Seagen, Exact Sciences, Gilead, Daiichi Sankyo, Stemline. Gluz, Oleg: Honoraria/consulting: Roche, Celgene, Amgen, Seagen, Novartis, Lilly, Pfizer, MSD, Exact Sciences, Gilead, AstraZeneca, Molecular Health, Pierre Fabre, Eisai, Agendia. Travel support: Daiichi Sankyo, Roche, Pfizer. Non-Profit: Gesellschafter Westdeutsche Studiengruppe GmbH. Park-Simon, Tjoung-Won: Roche, AstraZeneca, GSK, Pfizer, Daiichi Sankyo, Lilly, MSD, NCO, Eisai, Seagen, Exact Sciences, Novartis, Gilead, Onkowissen, ONKO-Internetportal. Meeting support: Amgen, Roche, Celgene, Gilead, Pfizer, Novartis, AstraZeneca, MSD, Teva, TESARO, GSK, Clovis Oncology, Pharmamar, Pierre Fabre, Gedeon Richter, Eisai, Daiichi Sankyo, Hexal, Ribosepharm, Schering, BMS, Janssen-Cilag, Olympus, Seagen, Genomic Health. Travel support: Pfizer, Roche, Eisai, Pierre Fabre, MSD, Gilead, Stryker. Research support: Roche. Untch, Michael: Honoraria: AstraZeneca, Art tempi, Amgen, Daiichi Sankyo, Lilly, Roche, Pfizer, MSD Oncology, Pierre Fabre, Sanofi-Aventis, Myriad, Seagen, Gilead, Novartis, Menarini Stemline. Consulting or advisory role: Amgen, Lilly, Roche, CD Pharma, Pfizer, Pierre Fabre, Novartis, MSD Oncology, Agendia, Seagen, Gilead, Menarini Stemline, Genzyme. All honoraria and fees to the employer/institution. Lux, Michael Patrick: 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., (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/).)

Purpose: This study analyzes levels of social participation in patients with breast cancer on average 5 years following primary surgery as compared to women in the general population. In addition, the role of breast cancer-related complaints and medical data as possible influencing factors on levels of patients' social participation is investigated., Methods: A total of n = 454 patients after primary surgery (t0) were recruited for a third follow-up study, and n = 372 completed this survey (t3), corresponding to a response rate of 82.2%. For measuring breast cancer-related complaints, participants completed a written questionnaire. Social participation was measured by a questionnaire on different leisure activities that was taken from the Socio-Economic Panel Study. Medical information was extracted from medical reports at t0. A principal component analysis was carried out to identify different dimensions of social participation. Chi 2 -tests and logistic regression analyses were applied to analyze social participation as compared to the general population and the role of possible medical and diagnosis-related influencing factors thereby., Results: Compared to the general population, patients show lower levels of social participation in the domains "socio-cultural participation" and "participation in institutions," while no significant differences for "social participation in the private sphere" and "social participation via social media" were found. Psychological symptoms, pain, and a history of mastectomy were most strongly associated with restrictions in social participation., Conclusions: Our study suggests that social withdrawal may happen due to disease-related symptoms, preventing some breast cancer patients from participating fully in society. Cancer-related follow-ups should address this issue and support patients' reintegration into society through appropriate therapeutic interventions., (© 2024. The Author(s).)

The Breast Committee of the Arbeitsgemeinschaft Gynäkologische Onkologie (German Gynecological Oncology Group, AGO) presents the 2024 update of the evidence-based recommendations for the diagnosis and treatment of patients with locally advanced and metastatic breast cancer., Competing Interests: Prof. Dr. med. Marc Thill was a member of advisory board Agendia, Amgen, AstraZeneca, Aurikamed, Becton/Dickinson, Biom‘Up, ClearCut, Clovis, Daiichi Sankyo, Eisai, Exact Sciences, Gilead Science, Grünenthal, GSK, Lilly, MSD, Neodynamics, Novartis, Onkowissen, Organon, Pfizer, pfm medical, Pierre Fabre, Roche, RTI Surgical, Seagen, Sirius Medical, and Sysmex; received manuscript support from Amgen, ClearCut, Clovis, Organon, pfm medical, Roche, and Servier; received travel expenses from Amgen, Art Tempi, AstraZeneca, Clearcut, Clovis, Connect Medica, Daiichi Sankyo, Eisai, Exact Sciences, Gilead, Hexal, I-Med-Institute, Lilly, MCI, MSD, Neodynamics, Novartis, Pfizer, pfm medical, Roche, RTI Surgical, and Seagen; received congress support from Amgen, AstraZeneca, Celgene, Daiichi Sanyko, Gilead, Hexal, Lilly, Neodynamics, Novartis, Pfizer, Pierre Fabre, Roche, and Sirius Medical; has received lecture honoraria from Amgen, Art Tempi, AstraZeneca, Clovis, Connect Medica, Eisai, Exact Sciences, Gedeon Richter, Gilead Science, GSK, Hexal, I-Med-Institute, Jörg Eickeler, Laborarztpraxis Walther et al. Lilly, MCI, Medscape, MSD, Medtronic, Novartis, Onkowissen, Pfizer, pfm medical, Roche, Seagen, StreamedUp, Stemline, Sysmex, Vifor, Viatris, and ZP Therapeutics; has received trial funding from Endomag, Exact Sciences; and received trial honoraria (institutional) from AstraZeneca, Biom’Up, Cairn Surgical, Celgene, Clearcut, Neodynamics, Novartis, pfm medical, Roche, and RTI Surgical. Prof. Dr. med. Wolfgang Janni has received research grants and/or honoraria from AstraZeneca, Celgene, Chugai, Daiichi Sankyo, Eisai, ExactScience, GSK, Janssen, Lilly, Menarini, MSD, Novartis, Sanofi Aventis, Roche, Pfizer, Seagen, Gilead, Inivata, and Guardant Health. Prof. Dr. med. Ute-Susann Albert has received lectures from Pfizer, Novartis, AstraZeneca, was a member of advisory board Daiichi Sankyo, and Pfizer. Prof. Dr. Malgorzata Banys-Paluchowski has received honoraria for lectures and advisory from Roche, Novartis, Pfizer, pfm, Eli Lilly, Onkowissen, Seagen, AstraZeneca, Eisai, Amgen, Stemline, Samsung, Canon, MSD, GSK, Daiichi Sankyo, Gilead, Sirius Medical, Syantra, Pierre Fabre, and ExactSciences; received study support from EndoMag, Mammotome, MeritMedical, Gilead, Hologic, and ExactSciences; and received travel/congress support from Eli Lilly, ExactSciences, Pierre Fabre, Pfizer, AstraZeneca, Daiichi Sankyo, and Roche. Dr. med. Ingo Bauerfeind has received honoraria and travel reimbursement from Brustkrebs Deutschland e.V., Krankenhaus Kempten, Akademie für Psychoonkologie, IF-Kongress Management. Prof. Dr. med. Jens-Uwe Blohmer has received honoraria for advisory boards and lectures from Astra Zeneca, Daiichi Sankyo, Eisai, Gilead, Lilly, MSD, Novartis, Pfizer, Roche, and Seagen. Prof. Dr. med. Wilfried Budach has received honoraria for lectures and advisory boards from Merck, BMS, Jörg Eickeler Veranstaltungen, medpublico GmbH, and BVDST. Prof. Dr. med. Peter Dall has received honoraria for lectures and advisory boards from Novartis, Pierre Fabré, MSD, Lilly, and AstraZeneca. Prof. Dr. Nina Ditsch was a member of advisory boards and speakers bureaus AstraZeneca, Aurikamed, BGGF, Daiichi Sankyo, Elsevier Verlag, ESO, Exact Sciences, Gilead Sciences, GSK, if-Kongress, KelCon, Leopoldina Schweinfurt, Lilly, Lukon, Molekular Health, MSD, Novartis, onkowissen, Pfizer, RG-Ärztefortbildungen, Roche, and Seagen. Prof. Dr. med. Eva Maria Fallenberg has received research grant from DFG and speaker honorarium from GE Healthcare, Bayer Healthcare, Guerbet, Siemens, BD, Roche, EUSOBI, ESOR, ESMO, and B-Rayz. Prof. Dr. med. Peter A. Fasching participate on a data safety monitoring board or advisory board: Novartis, Pfizer, Roche, Daiichi Sankyo, AstraZeneca, Lilly, Eisai, Merck Sharp and Dohme, Pierre Fabre, SeaGen, Agendia, Sanofi Aventis, Gilead, and Mylan; has received honoraria for lecture, speakers bureaus, manuscript writing, or educational events from Novartis, Pfizer, Roche, Daiichi Sankyo, AstraZeneca, Lilly, Eisai, Merck Sharp and Dohme, Pierre Fabre, SeaGen, Agendia, Sanofi Aventis, Gilead, and Mylan; and has received consulting from Novartis, Pfizer, Roche, Daiichi Sankyo, AstraZeneca, Lilly, Eisai, Merck Sharp and Dohme, Pierre Fabre, SeaGen, Agendia, Sanofi Aventis, Gilead, and Mylan. Medical Writing: Merck, to institution: Biontech, Cepheid, Pfizer. Prof. Dr. med. Tanja N. Fehm has receiverd honoraria from Onkowissen. Prof. Dr. med. Michael Friedrich was a member of advisory board: Gilead Sciences has received other honoraria from Roche, MSD. Prof. Dr. med. Bernd Gerber has received travel support from Pfizer. PD Dr. med. Oleg Gluz has received honoraria for lectures and/or consulting from Amgen, AstraZeneca, Daiichi Sanyko, Eisai, Gilead Science, Lilly, MSD, Novartis, Pfizer, Roche, Seagen, Exact Sciences, Agendia, MedConcept, and GynUpdate, Minority share holder: Westdeutsche Studiengruppe (WSG). Prof. Nadia Harbeck, MD has received honoraria for lectures and/or consulting from AstraZeneca, Daiichi Sankyo, Gilead, Lilly, MSD, Novartis, Pierre Fabre, Pfizer, Roche, Seagen, Viatris, and Zuelligpharma; received other from Co-Director West German Study Group (WSG). Prof. Dr. med. Andreas Daniel Hartkopf has received honoraria for consulting and speaking engagements from AstraZeneca, Agendia, Amgen, Clovis, Daichi Sankyo, Eisai, ExactScience, Gilead, GSK, Hexal, Lilly, MSD, Novartis, Onkowissen, Pfizer, Roche, Pierre Fabre, Seagen, Stemline, and Verazyte. Prof. Dr. med. Jens Huober has received honoraria for lectures from Lilly, Novartis, Roche, Pfizer, AstraZeneca, MSD, Seagen, Gilead, and Daiichi; has received honoraria for consulting/advisory board from Lilly, Novartis, Roche, Pfizer, AstraZeneca, MSD, Daiichi, and Gilead; and has received travel grants from Roche, Pfizer, Daiichi, and Gilead. Prof. Dr. med. Christian Jackisch was a member of advisory board Astra Zeneca, Novartis, Lilly, Gilead, Exact Sciences, Pfizer, Roche, GSK, Pierre Fabre, Roche, and Seagen and received lecture from Art tempi, AstraZeneca, Lilly, Novartis, Roche, Amgen, Pierre Fabre, Exact Sciences, MSD, GynUpdate, and StreamedUp. Prof. Dr. med. Cornelia Kolberg-Liedtke was a member of advisory board: SeaGen, Exact Sciences, Pfizer, Novartis, AstraZeneca, Lilly, SeaGen, Daiichi Sankyo, Agendia, Gilead, and Onkowissen; has received lecture from NOGGO, CECOG, PINK, Pfizer, Roche, AstraZeneca, Carl Zeiss Meditec, Lilly, SeaGen, and Daiichi Sankyo; received other honoraria from Gilead Science and POMME; and stockholding Theraclion SA. Prof. Dr. med. Hans-Heinrich Kreipe was a member of advisory board: Lilly; has received lecture from AstraZeneca, Roche, Daiichi Sankyo, and Pfizer. PD Dr. David Krug has received lecture from Merck Sharp and Dohme, Pfizer, Astra Zeneca, onkowissen, med update; was a member of advisory board: Gilead; and has received research funding from Merch KGaA and Deutsche Krebshilfe. Prof. Dr.med. Thorsten Kühn was a member of advisory board/lecture Sysmex, Neodynamics, Pfizer, MSD, Merit Medical, Sirius Medical, Hologic, Endomag, Lilly; and has received trial funding from Merit Medical, Endomag, Mammotome. Prof. Dr. med. Sherko Kümmel has received lecture from Roche, Lilly, Exact Sciences, Novartis, Amgen, Daiichi Sankyo, AstraZeneca, MSD, Pfizer, Seagen, Gilead, Agendia; Hologic, PINK!, and Stemline; has received other honoraria from Roche, Daiichi Sankyo, and Sonoscape; was a member of advisory board Lilly, MSD, Roche, Astra Zeneca, Stemline, Novartis, Daiichi Sankyo, MSD, Seagen, Gilead, and Exact Science. Prof. Dr. med. Sibylle Loibl was a member of advisory board, institutional: Abbvie, Amgen, AstraZeneca, BMS, Celgene, DSI, Eirgenix, GSK, Gilead Science, Lilly, Novartis, Olema, Pfizer, Pierre Fabre, Relay Therapeuticas, Puma, Roche, Seagen, and Stemline-Menarini; invited speaker, personal: Medscape; and has received trial funding/others from Astra Zeneca, Abbvie, Celgene, Daiichi Sankyo, Greenwich Life Sciences, GSK, Immunomedics/Gilead, Molecular Health, Novartis, Pfizer, Roche, Stemline-Menarini, and VM Scope GmbH. Prof. Dr. med. Diana Lüftner D.L. has received honoraria for advisory board activities and/or oral presentations from Amgen, AstraZeneca, Daiichi Sankyo, Eli Lilly, Gilead, GSK, high5md, Loreal, MSD, Mundipharma, Novartis, onkowissen.de, Pfizer, Pierre Fabre, Roche, and TEVA. Prof. Dr. med. Michael Patrick Lux 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. Prof. Dr. med. Nicolai Maass was a member of advisory board Amgen, AstraZeneca, Clovis, Daiichi Sankyo, GSK, Lilly, MSD, Novartis, Pierre Fabre, Pfizer, Roche, and Seagen has received lecture from Astra Zeneca, Daiichi Sankyo, GSK, Lilly, Novartis, Pfizer, and Roche. Prof. Dr. med. Christoph Mundhenke was a member of advisory board AstraZeneca, Pfizer, Daiichi Sankyo, Seagen, and Novartis and has received lecture from Pfizer and Novartis. Prof. Dr. med. Toralf Reimer has received trial funding from German Cancer Aid and Else Kroener-Fresenius-Stiftungwas a member of advisory board MSD, Novartis, and Myriad; and has received lecture from Pfizer, Novartis, Roche, and AstraZeneca. Prof. Dr. med. Kerstin Rhiem has received honoraria from AstraZeneca, Roche, Novartis, streamed up. Prof. Dr. med. Achim Rody was a member of advisory board AstraZeneca, Novartis, Roche, Exact Sciences, Pierre Fabre, Lilly, Seagen, Amgen, MSD, Gilead; has received lecture from Pfizer, Celgene, Eisai; and has received trial funding from Eisai. Prof. Dr. med. Marcus Schmidt M.S. reports personal fees from AstraZeneca, BioNTech, Daiichi Sankyo, Eisai, GILEAD, Lilly, Menarini-Stemline, Molecular Health, MSD, Novartis, Pantarhei Bioscience, Pfizer, Pierre Fabre, Roche, and SeaGen, His institution has received research funding from AstraZeneca, BioNTech, Eisai, Genentech, German Breast Group, Novartis, Palleos, Pantarhei Bioscience, Pierre Fabre, and SeaGen. In addition, he has a patent for EP 2390370 B1 and a patent for EP 2951317 B1 issued. Prof. Dr. med. Andreas Schneeweiss has received research grants from Celgene, Roche; has received honoraria from Amgen, AstraZeneca, Aurikamed, Bayer, Celgene, ClinSol, Clovis Oncology, coma UroGyn, Connectmedica, Daiichi Sankyo, Gilead, GSK, if-kongress, I-MED, iOMEDICO, Lilly, MCI Deutschland, med publico, Metaplan, MSD, Mylan, NanoString Technologies, Novartis, onkowissen.de, Pfizer, Pierre Fabre, promedicis, Roche, Seagen, streamedup, and Tesaro; and has received travel support from AstraZeneca, Celgene, Daiichi Sankyo, Gilead, Pfizer, and Roche. Prof. Dr. med. Florian Schütz has received lecture from Amgen, AstraZeneca, Daiichi Sankyo, Eisai, ExactSciences, Gilead, Lilly, MSD, Novartis, ClinSol, Pfizer, and Roche Pharma; was a member of advisory board Lilly, MSD, Gilead, Atheneum Partners, and ClinSol; and received travel expenses from Lilly, Gilead. Prof. Dr. med. Hans-Peter Sinn was a member of advisory board Astra Zeneca, Exact Sciences, and Daiichi Sankyo; has received lecture from AstraZeneca and Diacentus; and has received trial funding from AstraZeneca. Prof. Dr. med. Christine Solbach has received lecture from DiaLog Service GmbH, Jörg Eickeler, Pfizer, Roche, AstraZeneca, MedConcept, I-Med, GBG, BVF Akademie, and LÄK Hessen Akademie was a member of advisory board: MSD, Roche. Prof. Dr. med. Erich Solomeyer has received honoraria from Roche, Amgen, Celgen, Tesaro, Astra Zeneca, Pfizer, Storz, Erbe, Gedeon Richter, Eisai, Medac, MSD, Vifor, Teva, Ethikon, Johnson Johnson, Daiichi Sankyo, Gilead, Exact Sciences, GSK, and Pierre Fabre. Prof. Dr. med. Elmar Stickeler was a member of advisory boards Amgen, Astra Zeneca, Gilead, Iomedico, Lilly, MSD, Novartis, Seagen, and Roche and received lecture from Astra Zeneca, BSH Düsseldorf, Gilead, Iomedico, MSD, Novartis, Onkowissen, Pfizer, PharmaMar, and Roche. Prof. Dr. med. Christoph Thomssen has received compensation for advisory boards, lectures or publications from Amgen, AstraZeneca, Aurikamed, Daiichi Sankyo, Forum Sanitas, Gilead, Jörg Eickeler, Hexal, Lilly, Medupdate, MSD, Nanostring, Novartis, Onkowissen, Pfizer, Roche, Seagen, Vifor. Prof. Dr. med. Michael Untch M. U. has received honoraria to travel support, lectures, and consulting or advisory role from AstraZeneca, Amgen, Daiichi Sankyo, Lilly, Roche, Pfizer, MSD Oncology, Pierre Fabre, Sanofi Aventis, Myriad, Seagen, Novartis, Gilead, Stemline, Genzyme, Agendia, Onkowissen, and Eisai, all honoraria and fees to the employer/institution. Prof. Dr. Isabell Witzel has received lecture from Astra Zeneca, Lilly, Seagen, Daiichi Sankyo, Gilead, Pfizer and Novartis, and Onkowissen and has received Travel support from Roche and Lilly. Prof. Dr. med. Achim Wöckel has received compensation for advisory boards, lectures, trial funding advisory board from Amgen, AstraZeneca, Aurikamed, Celgene, Eisai, Lilly, Novartis, Pfizer, Roche, Tesaro, Sirtex, MSD, Exact Sciences, Pierre Fabre, Clovis, Organon, Daiji Sankyo, Seagen, Stemline, and Gilead. PD. Dr. Rachel Würstlein served as advisor, consultant, speaker, and travel grant Agendia, Amgen, Apogepha, Aristo, Astra Zeneca, Celgene, Clovis Oncology, Daiichi Sankyo, Eisai, Esteve, Exact Sciences, Gilead, 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, and MediSeminar. Prof. Dr. med. Volkmar Müller has received speaker honoraria Astra Zeneca, Daiichi Sankyo, Eisai, Pfizer, MSD, Medac, Novartis, Roche, Seagen, Onkowissen, high5 Oncology, Medscape, Gilead, Pierre Fabre, and i-MED Institute; has received consultancy honoraria from Roche, Pierre Fabre, PINK, ClinSol, Novartis, MSD, Daiichi Sankyo, Eisai, Lilly, Seagen, Gilead, and Stemline; has received institutional research support from Novartis, Roche, Seagen, Genentech, and Astra Zeneca; and has received travel grants from Astra Zeneca, Roche, Pfizer, Daiichi Sankyo, and Gilead. Prof. Dr. Tjoung-Won Park-Simon has received honoraria for lectures and/or consulting from Roche, AstraZeneca, GSK, Pfizer, Lilly, MSD, Exact Sciences, Daiichi Sankyo, Seagen, Novartis, Gilead Science, NCO, Onkowissen, Exact Sciences, and Seagen and has received travel compensation from Roche, AstraZeneca, Pfizer, Lilly, Daiichi Sankyo, Gilead, and Pierre Fabre. Prof. Dr. med. Jörg Heil has none to declare., (© 2024 S. Karger AG, Basel.)

Introduction: Each year the interdisciplinary AGO (Arbeitsgemeinschaft Gynäkologische Onkologie, German Gynecological Oncology Group) Breast Committee on Diagnosis and Treatment of Breast Cancer provides updated state-of-the-art recommendations for early and metastatic breast cancer., Methods: The updated evidence-based treatment recommendations for early and metastatic breast cancer have been released in March 2024., Results and Conclusion: This paper concisely captures the updated recommendations for early breast cancer chapter by chapter., Competing Interests: Prof. Dr. Tjoung-Won Park-Simon has received honoraria for lectures and/or consulting from Roche, AstraZeneca, GSK, Pfizer, Lilly, MSD, ExactSciences, Daiichi Sankyo, Seagen, Novartis, Gilead Science, NCO, Onkowissen, Exact Sciences, Seagen. Travel compensation: Roche, AstraZeneca, Pfizer, Lilly, Daiichi Sankyo, Gilead, and Pierre Fabre. Prof. Dr. med. Ute-Susann Albert has received honoraria for lectures from Pfizer, Novartis, AstraZeneca and is a member of advisory board Daiichi Sankyo, Pfizer. Prof. Dr. Malgorzata Banys-Paluchowski has received honoraria for lectures and advisory from Roche, Novartis, Pfizer, pfm, Eli Lilly, Onkowissen, Seagen, AstraZeneca, Eisai, Amgen, Stemline, Samsung,Canon, MSD, GSK, Daiichi Sankyo, Gilead, Sirius Medical, Syantra, Pierre Fabre, ExactSciences, study support from EndoMag, Mammotome, Merit Medical, Gilead, Hologic, ExactSciences, and travel/congress support from Eli Lilly, ExactSciences, Pierre Fabre, Pfizer, AstraZeneca, Daiichi Sankyo, and Roche. Prof. Dr. med. Jens-Uwe Blohmer has received honoraria for advisory boards and lectures: AstraZeneca, Daiichi Sankyo, Eisai, Gilead, Lilly, MSD, Novartis, Pfizer, Roche, Seagen. Prof. Dr. med. Wilfried Budach has received honoraria for lectures and advisory boards: Merck, BMS, Jörg Eickeler Veranstaltungen, med publico GmbH, BVDST. Prof. Dr. med. Peter Dall has received honoraria for lectures and advisory boards from Novartis, Pierre Fabré, MSD, Lilly, AstraZeneca. Prof. Dr. Nina Ditsch was a member of advisory boards and speakers bureaus: AstraZeneca, Aurikamed, BGGF, Daiichi-Sankyo, Elsevier Verlag, ESO, Exact Sciences, Gilead Sciences, GSK, if-Kongress, KelCon, Leopoldina Schweinfurt, Lilly, Lukon, Molekular Health, MSD, Novartis, Onkowissen, Pfizer, RG-Ärztefortbildungen, Roche, Seagen. Prof. Dr. med. Eva Maria Fallenberg has received research grant from DFG and received speaker honorarium from GE Healthcare, Bayer Healthcare, Guerbet, Siemens, BD, Roche, EUSOBI, ESOR, ESMO, B-Rayz. Prof. Dr. med. Peter A. Fasching: participation on a data safety monitoring board or advisory board: Novartis, Pfizer, Roche, Daiichi-Sankyo, AstraZeneca, Lilly, Eisai, Merck Sharp and Dohme, Pierre Fabre, SeaGen, Agendia, Sanofi Aventis, Gilead, Mylan, has received honoraria for lecture, speakers bureaus, manuscript writing, or educational events from Novartis, Pfizer, Roche, Daiichi-Sankyo, AstraZeneca, Lilly, Eisai, Merck Sharp and Dohme, Pierre Fabre, SeaGen, Agendia, Sanofi Aventis, Gilead, Mylan, consulting from Novartis, Pfizer, Roche, Daiichi-Sankyo, AstraZeneca, Lilly, Eisai, Merck Sharp and Dohme, Pierre Fabre, SeaGen, Agendia, Sanofi Aventis, Gilead, Mylan. Medical Writing: Merck. To institution: Biontech, Cepheid, Pfizer. Prof. Dr. med. Michael Friedrich is a member of the advisory board Gilead Sciences and has received other honoraria from Roche, MSD. Prof. Dr. med. Bernd Gerber has received travel support from Pfizer. PD Dr. med. Oleg Gluz has received honoraria for lectures and/or consulting from Amgen, AstraZeneca, Daiichi Sanyko, Eisai, Gilead Science, Lilly, MSD, Novartis, Pfizer, Roche, Seagen, Exact Sciences, Agendia, MedConcept, GynUpdate, and minority share holder: Westdeutsche Studiengruppe (WSG). Prof. Nadia Harbeck, MD has received honoraria for lectures and/or consulting from AstraZeneca, Daiichi-Sankyo, Gilead, Lilly, MSD, Novartis, Pierre Fabre, Pfizer, Roche, Seagen, Viatris, Zuelligpharma, other are Co-Director West German Study Group (WSG). Prof. Dr. med. Andreas Daniel Hartkopf has received honoraria for consulting and speaking engagements from AstraZeneca, Agendia, Amgen, Clovis, DaichiiSankyo, Eisai, Exact Science, Gilead, GSK, Hexal, Lilly, MSD, Novartis, Onkowissen, Pfizer, Roche, Pierre Fabre, Seagen, Stemline, and Verazyte. Prof. Dr. med. Jens Huober has received honoraria for lectures: Lilly, Novartis, Roche, Pfizer, AstraZeneca, MSD, Seagen, Gilead, Daiichi and honoraria for consulting/advisory board: Lilly, Novartis, Roche, Pfizer, AstraZeneca, MSD, Daiichi, Gilead and received travel grants: Roche, Pfizer, Daiichi, Gilead. Prof. Dr. med. Christian Jackisch is a member of advisory board: AstraZeneca, Novartis, Lilly, Gilead, Exact Sciences, Pfizer, Roche, GSK, Pierre Fabre, Roche, Seagen; Lecture: Art tempi, AstraZeneca, Lilly, Novartis, Roche, Amgen, Pierre Fabre, Exact Sciences, MSD, GynUpdate, StreamedUp. Prof. Dr. med. Cornelia Kolberg-Liedtke is a member of advisory board: SeaGen, Exact Sciences, Pfizer, Novartis, AstraZeneca, Lilly, SeaGen, Daiichi Sankyo, Agendia, Gilead, Onkowissen, has received honoraria for lectures from NOGGO, CECOG, PINK, Pfizer, Roche, AstraZeneca, Carl Zeiss Meditec, Lilly, SeaGen, Daiichi Sankyo. Other: Gilead Science, POMME. Stockholding: Theraclion SA. Prof. Dr. med. Hans-Heinrich Kreipe is a member of advisory board: Lilly, has received honoraria for lecture: AstraZeneca, Roche, Daiichi Sankyo, Pfizer. PD Dr. David Krug has received honoraria for lecture from Merck Sharp and Dohme, Pfizer, AstraZeneca, Onkowissen, med update is a member of advisory board: Gilead, has received research funding from Merch KGaA, Deutsche Krebshilfe. Prof. Dr. med. Thorsten Kühn is a member of advisory board/lecture: Sysmex, Neodynamics, Pfizer, MSD, Merit Medical, Sirius Medical, Hologic, Endomag, Lilly has received trial funding from Merit Medical, Endomag, Mammotome. Prof. Dr. med. Sherko Kümmel has received honoraria for lecture: Roche, Lilly, Exact Sciences, Novartis, Amgen, Daiichi Sankyo, AstraZeneca, MSD, Pfizer, Seagen, Gilead, Agendia; Hologic, PINK!; Stemline, other honoraria from Roche, Daiichi Sankyo, Sonoscape, is a member of advisory board: Lilly, MSD, Roche, AstraZeneca, Stemline, Novartis, Daiichi Sankyo, MSD, Seagen, Gilead, Exact Science. Prof. Dr. med. Sibylle Loibl is a member of advisory board, institutional: Abbvie, Amgen, AstraZeneca, BMS, Celgene, DSI, Eirgenix, GSK, Gilead Science, Lilly, Novartis, Olema, Pfizer, Pierre Fabre, Relay Therapeuticas, Puma, Roche, Seagen, Stemline-Menarini, invited speaker, personal: Medscape received trial funding/others from: AstraZeneca, Abbvie, Celgene, Daiichi-Sankyo, Greenwich Life Sciences, GSK, Immunomedics/Gilead, Molecular Health, Novartis, Pfizer, Roche, Stemline-Menarini, VM Scope GmbH. Prof. Dr. med. Diana Lüftner has received honoraria for advisory board activities and/or oral presentations from Amgen, AstraZeneca, Daiichi Sankyo, Eli Lilly, Gilead, GSK, high5md, Loreal, MSD, Mundipharma, Novartis, onkowissen.de, Pfizer, Pierre Fabre, Roche and TEVA. Prof. Dr. med. Michael Patrick Lux 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. Prof. Dr. med. Nicolai Maass was a member of advisory board: Amgen, AstraZeneca, Clovis, Daiichi Sankyo, GSK, Lilly, MSD, Novartis, Pierre Fabre, Pfizer, Roche, Seagen and has received honoraria for lectures from AstraZeneca, Daiichi Sankyo, GSK, Lilly, Novartis, Pfizer, Roche. Prof. Dr. med. Christoph Mundhenke was a member of advisory board: AstraZeneca, Pfizer, Daiichi Sankyo, Seagen, Novartis, has received honoraria for lecture: Pfizer, Novartis. Prof. Dr. med. Toralf Reimer has received trial funding from German Cancer Aid and Else Kroener-Fresenius-Stiftung, is a member of advisory board: MSD, Novartis, Myriad lecture from: Pfizer, Novartis, Roche, AstraZeneca. Prof. Dr. med. Achim Rody was a member of advisory board: AstraZeneca, Novartis, Roche, Exact Sciences, Pierre Fabre, Lilly, Seagen, Amgen, MSD, Gilead, lecture Pfizer, Celgene, Eisai, has received trial funding from Eisai. Prof. Dr. med. Marcus Schmidt reports personal fees from AstraZeneca, BioNTech, Daiichi Sankyo, Eisai, GILEAD, Lilly, Menarini-Stemline, Molecular Health, MSD, Novartis, Pantarhei Bioscience, Pfizer, Pierre Fabre, Roche, and SeaGen, his institution has received research funding from AstraZeneca, BioNTech, Eisai, Genentech, German Breast Group, Novartis, Palleos, Pantarhei Bioscience, Pierre Fabre, and SeaGen. In addition, he has a patent for EP 2390370 B1 and a patent for EP 2951317 B1 issued. Prof. Dr. med. Andreas Schneeweiss has received research grants from Celgene, Roche, honoraria from Amgen, AstraZeneca, Aurikamed, Bayer, Celgene, ClinSol, Clovis Oncology, coma UroGyn, Connect Medica, Daiichi Sankyo, Gilead, GSK, if-kongress, I-MED, iOMEDICO, Lilly, MCI Deutschland, med publico, Metaplan, MSD, Mylan, NanoString Technologies, Novartis, onkowissen.de, Pfizer, Pierre Fabre, promedicis, Roche, Seagen, StreamedUp, and Tesaro, received travel support from AstraZeneca, Celgene, Daiichi Sankyo, Gilead, Pfizer, Roche. Prof. Dr. med. Florian Schütz has received honoraria for lecture Amgen, AstraZeneca, Daiichi Sankyo, Eisai, ExactSciences, Gilead, Lilly, MSD, Novartis, ClinSol, Pfizer, Roche Pharma, was a member of advisory board: Lilly, MSD, Gilead, Atheneum Partners, ClinSol, has received travel expenses from Lilly, Gilead. Prof. Dr. med. Hans-Peter Sinn was a member of advisory board: AstraZeneca, Exact Sciences, Daiichi Sankyo, has received honoraria for lecture from AstraZeneca, Diacentus, has received trial funding from AstraZeneca. Prof. Dr. med. Christine Solbach has received honoraria for lecture: DiaLog Service GmbH, Jörg Eickeler, Pfizer, Roche, AstraZeneca, MedConcept, I-Med, GBG, BVF Akademie, LÄK Hessen Akademie, was a member of advisory board: MSD, Roche. Prof. Dr. med. Elmar Stickeler was a member of advisory boards Amgen, AstraZeneca, Gilead, Iomedico, Lilly, MSD, Novartis, Seagen, Roche; has received honoraria for lecture: AstraZeneca, BSH Düsseldorf, Gilead, Iomedico, MSD, Novartis, Onkowissen, Pfizer, PharmaMar, Roche. Prof. Dr. med. Christoph Thomssen: compensation for advisory boards, lectures or publications. Amgen, AstraZeneca, Aurikamed, Daiichi-Sankyo, Forum Sanitas, Gilead, Jörg Eickeler, Hexal, Lilly, med update, MSD, Nanostring, Novartis, Onkowissen, Pfizer, Roche, Seagen, Vifor. Prof. Dr. med. Michael Untch has received honoraria to travel support, lectures, and consulting or advisory role from AstraZeneca, Amgen, Daiichi Sankyo, Lilly, Roche, Pfizer, MSD Oncology, Pierre Fabre, Sanofi-Aventis, Myriad, Seagen, Novartis, Gilead, Stemline, Genzyme, Agendia, Onkowissen, Eisai, all honoraria and fees to the employer/institution. Prof. Dr. Isabell Witzel has received honoraria for lecture: AstraZeneca, Lilly, Seagen, Daiichi Sankyo, Gilead, Pfizer and Novartis, Onkowissen. travel support from Roche and Lilly. Prof. Dr. med. Achim Wöckel compensation for advisory boards, lectures, trial funding Advisory board: Amgen, AstraZeneca, Aurikamed, Celgene, Eisai, Lilly, Novartis, Pfizer, Roche, Tesaro, Sirtex, MSD, Exact Sciences, Pierre Fabre, Clovis, Organon, Daiji Sankyo, Seagen, Stemline, Gilead. PD. Dr. Rachel Würstlein served as advisor, consultant, speaker, and travel grant from Agendia, Amgen, Apogepha, Aristo, AstraZeneca, Celgene, Clovis Oncology, Daiichi-Sankyo, Eisai, Esteve, Exact Sciences, Gilead, 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. Prof. Dr. med. Volkmar Müller has received speaker honoraria from: AstraZeneca, Daiichi-Sankyo, Eisai, Pfizer, MSD, Medac, Novartis, Roche, Seagen, Onkowissen, high5 Oncology, Medscape, Gilead, Pierre Fabre, iMED Institute, consultancy honoraria from Roche, Pierre Fabre, PINK, ClinSol, Novartis, MSD, Daiichi-Sankyo, Eisai, Lilly, Seagen, Gilead, Stemline, institutional research support from Novartis, Roche, Seagen, Genentech, AstraZeneca, travel grants form AstraZeneca, Roche, Pfizer, Daiichi Sankyo, Gilead. Prof. Dr. med. Wolfgang Janni has received research grants and/or honoraria from AstraZeneca, Celgene, Chugai, Daiichi Sankyo, Eisai, Exact Science, GSK, Janssen, Lilly, Menarini, MSD, Novartis, Sanofi-Aventis, Roche, Pfizer, Seagen, Gilead, Inivata, Guardant Health. Prof. Dr. med. Marc Thill is a member of advisory board: Agendia, Amgen, AstraZeneca, Aurikamed, Becton/Dickinson, Biom‘Up, ClearCut, Clovis, Daiichi Sankyo, Eisai, Exact Sciences, Gilead Science, Grünenthal, GSK, Lilly, MSD, Neodynamics, Novartis, Onkowissen, Organon, Pfizer, pfm Medical, Pierre Fabre, Roche, RTI Surgical, Seagen, Sirius Medical, Sysmex, has received manuscript support from Amgen, ClearCut, Clovis, Organon, pfm medical, Roche, Servier, has received travel expenses from Amgen, Art Tempi, AstraZeneca, Clearcut, Clovis, Connect Medica, Daiichi Sankyo, Eisai, Exact Sciences, Gilead, Hexal, I-Med-Institute, Lilly, MCI, MSD, Neodynamics, Novartis, Pfizer, pfm Medical, Roche, RTI Surgical, Seagen; Congress support: Amgen, AstraZeneca, Celgene, Daiichi Sanyko, Gilead, Hexal, Lilly, Neodynamics, Novartis, Pfizer, Pierre Fabre, Roche, Sirius Medical; Lecture honoraria: Amgen, Art Tempi, AstraZeneca, Clovis, Connect Medica, Eisai, Exact Sciences, Gedeon Richter, Gilead Science, GSK, Hexal, I-Med-Institute, Jörg Eickeler, Laborarztpraxis Walther et al., Lilly, MCI, Medscape, MSD, Medtronic, Novartis, Onkowissen, Pfizer, pfm medical, Roche, Seagen, StreamedUp, Stemline, Sysmex, Vifor, Viatris, ZP Therapeutics has received trial funding from Endomag, Exact Sciences, and trial honoraria from AstraZeneca, Biom’Up, Celgene, Clearcut, Neodynamics, Novartis, pfm medical, Roche, RTI Surgical. Prof. Dr. med. Jörg Heil: none to disclose. Dr. I. Bauerfeind received speaker honoraria from Brustkrebs Deutschland e.V., Krankenhaus Kempten, Akademie für Psychoonkologie, IF Kongressmanagement. Prof. Dr. med. Kerstin Rhiem received honoraria for lectures from AstraZeneca, Roche, Novartis, streamed up. Prof. Dr. med. Tanja N. Fehm received honoraria for lectures from Onkowissen. Prof. Dr. med. Erich-Franz Solomayer received honoraria for lectures and/or consulting from Roche, Amgen, Celgen, Tesaro, Astra Zeneca, Pfizer, Storz, Erbe, Gedeon Richter, Eisai, Medac, MSD, Vifor, Teva, Ethikon, Johnson Johnson, Daiichi-Sankyo, Gilead, Exact Sciences, GSK, Pierre Fabre., (© 2024 S. Karger AG, Basel.)

Sacituzumab govitecan (SG) is a new treatment option for patients with metastatic triple-negative and hormone receptor-positive, HER2-negative breast cancer. This antibody-drug conjugate is currently approved as monotherapy. Palliative radiotherapy is frequently used to treat symptomatic metastases locally. Concurrent use of SG and irradiation was excluded in clinical trials of SG, and there are currently limited published data. We report here a systematic review, as well as a retrospective multi-center study of 17 patients with triple-negative breast cancer who received concurrent SG and radiotherapy. In these patients, concurrent use was found to be efficient, safe and well tolerated. There were no apparent differences in moderate or severe acute toxicity according to the timing of SG administration.

Purpose: The interim analysis of the phase IIIb LUCY trial demonstrated the clinical effectiveness of olaparib in patients with germline BRCA-mutated (gBRCAm), human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer (mBC), with median progression-free survival (PFS) of 8.11 months, which was similar to that in the olaparib arm of the phase III OlympiAD trial (7.03 months). This prespecified analysis provides final overall survival (OS) and safety data., Methods: The open-label, single-arm LUCY trial of olaparib (300 mg, twice daily) enrolled adults with gBRCAm or somatic BRCA-mutated (sBRCAm), HER2-negative mBC. Patients had previously received a taxane or anthracycline for neoadjuvant/adjuvant or metastatic disease and up to two lines of chemotherapy for mBC., Results: Of 563 patients screened, 256 (gBRCAm, n = 253; sBRCAm, n = 3) were enrolled. In the gBRCAm cohort, median investigator-assessed PFS (primary endpoint) was 8.18 months and median OS was 24.94 months. Olaparib was clinically effective in all prespecified subgroups: hormone receptor status, previous chemotherapy for mBC, previous platinum-based chemotherapy (including by line of therapy), and previous cyclin-dependent kinase 4/6 inhibitor use. The most frequent treatment-emergent adverse events (TEAEs) were nausea (55.3%) and anemia (39.2%). Few patients (6.3%) discontinued olaparib owing to a TEAE. No deaths associated with AEs occurred during the study treatment or 30-day follow-up., Conclusion: The LUCY patient population reflects a real-world population in line with the licensed indication of olaparib in mBC. These findings support the clinical effectiveness and safety of olaparib in patients with gBRCAm, HER2-negative mBC., Clinical Trial Registration: Clinical trials registration number: NCT03286842., (© 2023. The Author(s).)

Survival from ovarian cancer depends on the resection status after primary surgery. We performed genome-wide association analyses for resection status of 7705 ovarian cancer patients, including 4954 with high-grade serous carcinoma (HGSOC), to identify variants associated with residual disease. The most significant association with resection status was observed for rs72845444, upstream of MGMT, in HGSOC (p = 3.9 × 10 -8 ). In gene-based analyses, PPP2R5C was the most strongly associated gene in HGSOC after stage adjustment. In an independent set of 378 ovarian tumours from the AGO-OVAR 11 study, variants near MGMT and PPP2R5C correlated with methylation and transcript levels, and PPP2R5C mRNA levels predicted progression-free survival in patients with residual disease. MGMT encodes a DNA repair enzyme, and PPP2R5C encodes the B56γ subunit of the PP2A tumour suppressor. Our results link heritable variation at these two loci with resection status in HGSOC., (© 2024. The Author(s).)

Background: Eribulin, a halichondrin-class microtubule dynamics inhibitor, is a preferred treatment option for patients with advanced breast cancer who have been pretreated with an anthracycline and a taxane. Peripheral neuropathy (PN) is a common side effect of chemotherapies for breast cancer and other tumors. The Incidence and Resolution of Eribulin-Induced Peripheral Neuropathy (IRENE) noninterventional postauthorization safety study assessed the incidence and severity of PN in patients with breast cancer treated with eribulin., Patients and Methods: IRENE is an ongoing observational, single-arm, prospective, multicenter, cohort study. Adult patients (≥18 years of age) with locally advanced or metastatic breast cancer and disease progression after 1-2 prior chemotherapeutic regimen(s) for advanced disease were treated with eribulin. Patients with eribulin-induced PN (new-onset PN or worsening of preexisting PN) were monitored until death or resolution of PN. Primary endpoints included the incidence, severity, and time to resolution of eribulin-induced PN. Secondary endpoints included time to disease progression and safety., Results: In this interim analysis (data cutoff date: July 1, 2019), 67 (32.4%) patients experienced any grade eribulin-induced PN, and 12 (5.8%) patients experienced grade ≥3 eribulin-induced PN. Median time to resolution of eribulin-induced PN was not reached. Median time to disease progression was 4.6 months (95% CI, 4.0-6.5). Treatment-emergent adverse events (TEAEs) occurred in 195 (93.8%) patients and serious TEAEs occurred in 107 (51.4%) patients., Conclusion: The rates of any grade and grade ≥3 eribulin-induced PN observed in this real-world study were consistent with those observed in phase III randomized clinical trials. No new safety findings were observed., (© The Author(s) 2023. Published by Oxford University Press.)

With more than 2.3 million newly diagnosed cases worldwide in 2020, breast cancer is still the most frequent cancer in women and despite improved diagnostics and treatment the most frequent cause of death from cancer. Continuous scientific developments in the areas of prevention, the application of modern diagnostic procedures and treatment options for early breast cancer, have led to an improvement in the 5‑year probability of survival. The treatment of early breast cancer is based on a combination of a locoregional and a systemic treatment approach. Depending on the tumor stage and the histological subtype the application of neoadjuvant chemotherapy with or without antibodies or immunotherapy is necessary. This article gives an overview of the current standard in the diagnostics and treatment of early breast cancer, without giving an in-depth elucidation of the differentiated subtype-specific systemic treatment. For this, reference should be made to the relevant literature., (© 2023. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Background: Polygenic risk score (PRS), calculated based on genome-wide association studies (GWASs), can improve breast cancer (BC) risk assessment. To date, most BC GWASs have been performed in individuals of European (EUR) ancestry, and the generalisation of EUR-based PRS to other populations is a major challenge. In this study, we examined the performance of EUR-based BC PRS models in Ashkenazi Jewish (AJ) women., Methods: We generated PRSs based on data on EUR women from the Breast Cancer Association Consortium (BCAC). We tested the performance of the PRSs in a cohort of 2161 AJ women from Israel (1437 cases and 724 controls) from BCAC (BCAC cohort from Israel (BCAC-IL)). In addition, we tested the performance of these EUR-based BC PRSs, as well as the established 313-SNP EUR BC PRS, in an independent cohort of 181 AJ women from Hadassah Medical Center (HMC) in Israel., Results: In the BCAC-IL cohort, the highest OR per 1 SD was 1.56 (±0.09). The OR for AJ women at the top 10% of the PRS distribution compared with the middle quintile was 2.10 (±0.24). In the HMC cohort, the OR per 1 SD of the EUR-based PRS that performed best in the BCAC-IL cohort was 1.58±0.27. The OR per 1 SD of the commonly used 313-SNP BC PRS was 1.64 (±0.28)., Conclusions: Extant EUR GWAS data can be used for generating PRSs that identify AJ women with markedly elevated risk of BC and therefore hold promise for improving BC risk assessment in AJ women., Competing Interests: Competing interests: BCAC conflict of interest: MWB conducts research funded by Amgen, Novartis and Pfizer. PAF conducts research funded by Amgen, Novartis and Pfizer. He received Honoraria from Roche, Novartis and Pfizer. JV is one ofthe inventors of diagnosis and treatment of ERCC3-mutant cancer. AWK has a research funding for his institution from Myriad Genetics for an unrelated project (funding dates 2017–2019). UM has research collaborations with Mercy BioAnalytics, RNA Guardian, Dana Farber and iLOF (Intelligent Lab on Fiber). RAM is a consultant for Pharmavite., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY. Published by BMJ.)

Background: Each year the interdisciplinary Arbeitsgemeinschaft Gynäkologische Onkologie (AGO), German Gynecological Oncology Group Breast Committee on Diagnosis and Treatment of Breast Cancer provides updated state-of-the-art recommendations for early and metastatic breast cancer., Summary: The updated evidence-based treatment recommendation for early and metastatic breast cancer has been released in March 2023., Key Messages: This paper concisely captures the updated recommendations for early breast cancer chapter by chapter., Competing Interests: Prof. Dr. Tjoung-Won Park-Simon. Honoraria for lectures and/or consulting: Roche, AstraZeneca, GSK, Pfizer, Lilly, MSD, Exact Sciences, Daiichi Sankyo, Seagen, Novartis, Gilead Science, NCO, Onkowissen, Exact Sciences, Seagen. Travel compensation: Roche, AstraZeneca, Pfizer. Prof. Dr. med. Ute-Susann Albert. Lectures: Pfizer, Novartis, AstraZeneca. Advisory board: Daiichi Sankyo. PD. Dr. Malgorzata Banys-Paluchowski. M.B. has received honoraria for lectures and advisory from Roche, Novartis, Pfizer, pfm, Eli Lilly, Onkowissen, Seagen, AstraZeneca, Eisai, Amgen, Samsung, Canon, MSD, GSK, Daiichi Sankyo, Gilead, Sirius Pintuition, Pierre Fabre and ExactSciences, study support from EndoMag, Mammotome, MeritMedical, Gilead, Hologic, ExactSciences, and travel/congress support from Eli Lilly, ExactSciences, Pierre Fabre, Pfizer, Daiichi Sankyo and Roche. Dr. med. Ingo Bauerfeind. Honoraria for lectures: Pfizer, Roche, Seagen. Prof. Dr. med. Jens-Uwe Blohmer. Honoraria for advisory boards and lectures: Astrazeneca, Daiichi Sankyo, Eisai, Gilead, Lilly, MSD, Novartis, Pfizer, Roche, Seagen Prof. Dr. med. Wilfried Budach. Lecture: Merck, BMS, Jörg Eickeler Veranstaltungen, medpublico GmbH, BVDST. Prof. Dr. med. Peter Dall, Honoraria for lectures and advisory boards: Novartis, Pierre Fabre, Gilead, MSD, Daiichi Sankyo, Lilly, AstraZeneca, Pfizer, Roche. Prof. Dr. Nina Ditsch. Advisory Boards and speakers bureaus. AstraZeneca, Aurikamed, BGGF, Daiichi-Sankyo, Elsevier Verlag, ESO, Exact Sciences, Gilead, GSK, if-Kongress, KelCon, Leopoldina Schweinfurt, Lilly, Lukon, Molekular Health, MSD, Novartis, onkowissen, Pfizer, RG-Ärztefortbildungen, Roche, Seagen Prof. Dr. med. Eva Maria Fallenberg. Research grant: DFG. Speaker honorarium: GE Healthcare, Bayer Healthcare, Guerbet, Siemens, BD, Roche, EUSOBI, ESOR, ESMO. Prof. Dr. med. Peter A. Fasching. Advisory board: Pfizer, Novartis, Roche, Daiichi Sankyo, Eisai, AstraZeneca, Lilly, MSD, Seagen, Agendia, Pierre Fabre, Sanofi Aventis, Gilead Science. Lecture: Pfizer, Novartis, Roche, Daiichi Sankyo, Eisai, AstraZeneca, Lilly, MSD, Seagen, Gilead Sciences. Other: Onkowissen, art tempi. Prof. Dr. med. Tanja N. Fehm. Onkowissen Prof. Dr. med. Michael Friedrich. Advisory Board: Gilead Sciences. Other honoraria: Roche, MSD. Prof. Dr. med. Bernd Gerber. Lecture honoraria: Roche, AstraZeneca, Seagen, Novartis, Pfizer, MedConcept. Others: Pfizer. PD Dr. med. Oleg Gluz. Honoraria for lectures and/or consulting: Amgen, AstraZeneca, Daiichi Sanyko, Gilead Science, Lilly, MSD, Novartis, Pfizer, Roche, Seagen, Exact Sciences, Agendia. Minority share holder: Westdeutsche Studiengruppe (WSG). Prof. Dr. med. Nadia Harbeck. Honoraria for lectures and/or consulting: Amgen, AstraZeneca, Daiichi Sanyko, Gilead, Lilly, MSD, Novartis, Pierre-Fabre, Pfizer, Roche, Sandoz, Sanofi, Seagen, Viatris, Zuelligpharma Minority share holder: Westdeutsche Studiengruppe (WSG). Prof. Dr. med. Andreas Hartkopf. Honoraria for consulting and speaking engagements from AstraZeneca, Agendia, Amgen, Clovis, DaichiiSankyo, Eisai, ExactScience, Gilead, GSK, Hexal, Lilly, MSD, Novartis, Onkowissen, Pfizer, Roche, Pierre-Fabre, Seagen, Stemline and Verazyte. Prof. Dr. med. Jörg Heil. None. Prof. Dr. med. Jens Huober. Trial funding: Novartis, Lilly. Honoraria for lectures: Lilly, Novartis, Roche, Pfizer, AstraZeneca, MSD, Celgene; Abbvie, Seagen, Gilead, Daiichi. Honoraria for consulting/advisory board: Lilly, Novartis, Roche, Pfizer, AstraZeneca, MSD, Abbvie, Daiichi, Gilead. Travel grants: Roche, Pfizer, Daiichi, Gilead. Prof. Dr. med. Christian Jackisch. Advisory board: Astra Zeneca, Novartis, Lilly, Gilead, Exact Sciences, Pfizer, Roche, GSK, Pierre-Fabre, Roche, Seagen; Lecture: Art tempi, AstraZeneca, Lilly, Novartis, Roche, Amgen, Pierre-Fabre, Exact Sciences, MSD, GynUpdate, StreamedUp. Prof. Dr. med. Cornelia Kolberg-Liedtke. Advisory board: SeaGen, Exact Sciences, Pfizer, Novartis, AstraZeneca, Lilly, SeaGen, Daiichi Sankyo, Agendia, Gilead, Onkowissen; Lecture: Novartis Ireland, NOGGO, CECOG, PINK, Pfizer, Roche, AstraZeneca, Carl Zeiss Meditec, Lilly, SeaGen, Daiichi Sankyo. Other: Gilead Science, POMME. Stockholding: Phaon Scientific, Theraclion SA. Trial Funding: Gilead Science. Prof. Dr. med. Hans-Heinrich Kreipe. Advisory board: Lilly. Lecture: AstraZeneca, Roche, Daiichi Sankyo, Pfizer. PD Dr. David Krug. Lecture: Merck Sharp & Dohme, onkowissen, Pfizer. Research funding: Merck KGaA. Advisory Board: Gilead. Prof. Dr.med. Thorsten Kühn. Advisory Board: Sysmex, Neodynamics. Trial funding: Merit Medical, Endomag, Mammotome. Lecture: Pfizer. Prof. Dr. med. Sherko Kümmel. Lecture: Roche, Lilly, Exact Sciences, Novartis, Amgen, Daiichi Sankyo, AstraZeneca, Somatex, MSD, Pfizer, pfm medical, Seagen, Gilead Science, Agendia. Other honoraria: Roche, Daiichi Sankyo, Sonoscape Advisory board: Lilly, MSD, Roche. Prof. Dr. med. Sibylle Loibl. Advisory Board, institutional: Abbvie, Amgen, AstraZeneca, BMS, Celgene, DSI, Eirgenix, GSK, Gilead Science, Lilly, Merck, Novartis, Olema, Pfizer, Pierre Fabre, Relay Therapeuticas, Puma, Roche, Samsung, Sanofi, Seagen Invited speaker, institutional: Astra Zeneca, DSI, Gilead, Novartis, Pfizer, Pierre Fabre, Roche, Seagen Invited speaker, personal: Medscape, Stemline-Menarini. Trial funding/others: Astra Zeneca, Abbvie, Celgene, Daiichi-Sankyo, Greenwich Life Sciences, Immunomedics/Gilead, Molecular Health, Novartis, Pfizer, Roche, Seagen, VM Scope GmbH. Prof. Dr. med. Diana Lüftner. Lecture: Lilly, Roche, MSD, Onkowissen, Novartis, Pfizer, Daiichi Sankyo, Gilead, AstraZeneca, Loreal, high4md. Advisory board: Lilly, Roche, MSD, Novartis, Pfizer, Daiichi Sankyo, Gilead, AstraZeneca, Other: Novartis. Prof. Dr. med. Michael Patrick Lux. M.P.L. has participated on advisory boards for AstraZeneca, Lilly, MSD, Novartis, Pfizer, Eisai, Gilead, Exact Sciences, Pierre Fabre, Grünenthal, Daiichi-Sankyo, PharmaMar, Roche, SamanTree, Sysmex and Hexal and has received honoraria for lectures from MSD, Lilly, Roche, Novartis, Pfizer, Exact Sciences, Daiichi-Sankyo, Grünenthal, pfm, Gilead, AstraZeneca, and Eisai. Prof. Dr. med. Nicolai Maass. Advisory board: Amgen, AstraZeneca, Clovis, Daiichi Sankyo, GSK, Lilly, MSD, Novartis, Pierre Fabre, Pfizer, Roche, Seagen Lecture: AstraZeneca, Daiichi Sankyo, GSK, Lilly, Novartis, Pfizer, Roche. Prof. Dr. med. Christoph Mundhenke. Advisory board: AstraZeneca, Pfizer, Daiichi Sankyo, Seagen, Novartis. Lecture: Pfizer, Novartis. Prof. Dr. med. Toralf Reimer. Trial funding: German Cancer Aid and Else Kroener-Fresenius-Stiftung. Advisory board: MSD, Novartis, Myriad. Lecture: Pfizer, Novartis, Roche, AstraZeneca. Prof. Dr. med. Kerstin Rhiem. Lecture: AstraZeneca, Amgen, Roche. Prof. Dr. med. Achim Rody. Advisory board: AstraZeneca, Novartis, Roche, Exact Sciences, Pierre Fabre, Lilly, Seagen, Amgen, MSD. Lecture: Pfizer, Celgene, Eisai. Trial funding: Eisai. Prof. Dr. med. Marcus Schmidt. MS reports personal fees from AstraZeneca, BioNTech, Daiichi Sankyo, Eisai, Lilly, MSD, Novartis, Pantarhei Bioscience, Pfizer, Pierre Fabre, Roche, and SeaGen, His institution has received research funding from AstraZeneca, BioNTech, Eisai, Genentech, German Breast Group, Novartis, Palleos, Pantarhei Bioscience, Pierre Fabre, and SeaGen. In addition, he has a patent for EP 2390370 B1 and a patent for EP 2951317 B1 issued. Prof. Dr. med. Andreas Schneeweiss. Lecture: Amgen, AstraZeneca, Aurikamed, Clinsol, ConnectMedica, Gilead Science, GSK, I-Med, Lilly, MSD, Nanostring, Novartis, Onkowissen, Promedicis, Pfizer, Pierre Fabre, Roche, Seagen, StreamedUp. Other: Thieme. Prof. Dr. med. Florian Schütz. Lecture: Amgen, AstraZeneca, Daiichi Sankyo, Eisai, ExactSciences, Gilead, Pfizer, MSD, Novartis, Onkowissen, Roche Pharma. Advisory board: Lilly, MSD, Atheneum Partners. Travel expanses: Lilly, Daiichi-Sankyo, Amgen, Prof. Dr. med. Hans-Peter Sinn. Advisory board: Exact Sciences, Daiichi Sankyo. Lecture: AstraZeneca. Trial Funding: AstraZeneca. Prof. Dr. med. Christine Solbach. Lecture: DiaLog Service GmbH, Jörg Eickeler, Pfizer, MedConcept, Medicultus, GBG, Dt. Röntgengesellschaft, BVF Akademie, LÄK Hessen Akademie, Meet the Expert Academy. Advisory board: MSD, Roche. Prof. Dr. med. Erich-Franz Solomayer. Roche, Amgen, Celgen, Tesaro, Astra Zeneca, Pfizer, Storz, Erbe, Gedeon Richter, Eisai, Medac, MSD, Vifor, Teva, Ethikon, Johnson Johnson, Daiichi-Sankyo, Gilead, Exact Sciences, GSK, Pierre Fabre. Prof. Dr. med. Elmar Stickeler. Advisory boards: Gilead, Iomedico, Lilly, MSD, Seagen Lecture: Pfizer, Bsh Düsseldorf, Gilead, Iomedico, PharmaMar, Onkowissen, Roche. Prof. Dr. med. Christoph Thomssen. Compensation for advisory boards, lectures or publications. Amgen, AstraZeneca, Aurikamed, Daiichi-Sankyo, Forum Sanitas, Gilead, Jörg Eickeler, Hexal, Lilly, Medupdate, MSD, Nanostring, Novartis, Onkowissen, Pfizer, Roche, Seagen, Vifor Prof. Dr. med. Michael Untch. M.U. has received honoraria for lectures and consulting or advisory role from AstraZeneca, Art tempi, Amgen, Daiji Sankyo, Lilly, Roche, Pfizer, MSD Oncology, Pierre Fabre, Sanofi-Aventis, Myriad, Seagen, Novartis, Gilead, Stemline, Genzyme, Agendia, Onkowissen, Eisai, All honoraria and fees to the employer/institution. Prof. Dr. Isabell Witzel. Lecture: Daiichi Sankyo, Pfizer, Roche, MSD, Lilly, Seagen, AstraZeneca, Gilead. Other: Onkowissen Prof. Dr. med. Achim Wöckel. Advisory board: Amgen, AstraZeneca, Aurikamed, Celgene, Eisai, Lilly, Novartis, Pfizer, Roche, Tesaro, Sirtex, MSD, Genomic Health, Pierre Fabre, Clovis, Organon. PD. Dr. Rachel Würstlein. Agendia, Amgen, Aristo, Astra Zeneca, Aurikamed, Celgene, Clinsol, Clovis Oncology, Daiichi-Sankyo, Eisai, Exact Sciences, FOMF, Gilead, Glaxo Smith Kline, Hexal, Lilly, MCI, medconcept, Medstrom Medical, MSD, Mundipharma, Mylan, Nanostring, Novartis, Odonate, Paxman, Palleos, Pfizer, Pierre Fabre, PINK, Pomme Med, PumaBiotechnolgogy, Riemser, Roche, Sandoz/Hexal, Sanofi Genzyme, Seattle Genetics/Seagen, Stemline, Tesaro Bio, Teva, Veracyte, Viatris Prof. Dr. med. Volkmar Müller. V.M. received speaker honoraria from Amgen, Astra Zeneca, Daiichi-Sankyo, Eisai, Pfizer, MSD, Novartis, Roche, Teva, Seattle Genetics, Genomic Health, Hexal, Roche, Pierre Fabre, ClinSol, Daiichi-Sankyo, Eisai, Lilly, Tesaro, Seattle Genetics and Nektar. Institutional research support from Novartis, Roche, Seattle Genetics, Genentech. Travel grants: Roche, Pfizer, Daiichi Sankyo. Prof. Dr. med. Wolfgang Janni. Lecture: Amgen, AstraZeneca, Daiichi Sankyo, Lilly, MSD, Novartis, Pfizer, Roche, Seagen, Gilead Science. Trial Funding: Amgen, AstraZeneca, Lilly, Novartis, Roche. Prof. Dr. med. Marc Thill. M.T. received personal fees for consulting from Agendia, Amgen, AstraZeneca, Aurikamed, Becton/Dickinson, Biom‘Up, ClearCut, Clovis, Daiichi Sankyo, Eisai, Exact Sciences, Gilead Science, Grünenthal, GSK, Lilly, MSD, Norgine, Neodynamics, Novartis, Onkowissen, Organon, Pfizer, pfm Medical, Pierre-Fabre, Roche, RTI Surgical, Seagen, Sirius Pintuition, Sysmex, for manuscript support from Amgen, ClearCut, Clovis, pfm medical, Roche, Servier, for travel expenses from Amgen, Art Tempi, AstraZeneca, Clearcut, Clovis, Connect Medica, Daiichi Sankyo, Eisai, Exact Sciences, Gilead, Hexal, I-Med-Institute, Lilly, MCI, Medtronic, MSD, Neodynamics, Norgine, Novartis, Pfizer, pfm Medical, Roche, RTI Surgical, Seagen, for congress support Amgen, AstraZeneca, Celgene, Daiichi Sanyko, Hexal, Neodynamics, Novartis, Pfizer, Roche, Sirius Medical, for lectures from Amgen, Art Tempi, AstraZeneca, Clovis, Connect Medica, Eisai, Exact Sciences, Gedeon Richter, Gilead Science, GSK, Hexal, I-Med-Institute, Jörg Eickeler, Laborarztpraxis Walther et al. Lilly, MCI, Medscape, MSD, Medtronic, Novartis, Onkowissen, Pfizer, pfm medical, Roche, Seagen, StreamedUp, Sysmex, Vifor, Viatris, for trial funding from Endomag, Exact Sciences and institutional fees from AstraZeneca, Biom’Up, Celgene, Clearcut, Neodynamics, Novartis, pfm medical, Roche, RTI Surgical., (© 2023 The Author(s). Published by S. Karger AG, Basel.)

The Breast Committee of the Arbeitsgemeinschaft Gynäkologische Onkologie (German Gynecological Oncology Group, AGO) presents the 2023 update of the evidence-based recommendations for the diagnosis and treatment of patients with locally advanced and metastatic breast cancer (mBC)., Competing Interests: The authors have the following conflicts of interest: Prof. Dr. Med. Marc Thill: MT received personal fees for consulting from Agendia, Amgen, AstraZeneca, Aurikamed, Becton/Dickinson, Biom‘Up, ClearCut, Clovis, Daiichi Sankyo, Eisai, Exact Sciences, Gilead Science, Grünenthal, GSK, Lilly, MSD, Norgine, NeoDynamics, Novartis, Onkowissen, Organon, Pfizer, pfm Medical, Pierre Fabre, Roche, RTI Surgical, Seagen, Sirius Pintuition, and Sysmex; for manuscript support from Amgen, ClearCut, Clovis, pfm medical, Roche, and Servier; for travel expenses from Amgen, Art Tempi, AstraZeneca, ClearCut, Clovis, ConnectMedica, Daiichi Sankyo, Eisai, Exact Sciences, Gilead, Hexal, I-Med-Institute, Lilly, MCI, Medtronic, MSD, NeoDynamics, Norgine, Novartis, Pfizer, pfm Medical, Roche, RTI Surgical, and Seagen; for congress support Amgen, AstraZeneca, Celgene, Daiichi Sankyo, Hexal, NeoDynamics, Novartis, Pfizer, Roche, and Sirius Medical; for lectures from Amgen, Art Tempi, AstraZeneca, Clovis, ConnectMedica, Eisai, Exact Sciences, Gedeon Richter, Gilead Science, GSK, Hexal, I-Med-Institute, Jörg Eickeler, Laborarztpraxis Walther, Lilly, MCI, Medscape, MSD, Medtronic, Novartis, Onkowissen, Pfizer, pfm medical, Roche, Seagen, STREAMED UP, Sysmex, Vifor, and Viatris; for trial funding from Endomag, Exact Sciences; and institutional fees from AstraZeneca, Biom’Up, Celgene, ClearCut, NeoDynamics, Novartis, pfm medical, Roche, and RTI Surgical. Prof. Dr. Med. Ute-Susann Albert, lectures: Pfizer, Novartis, and AstraZeneca; advisory board: Daiichi Sankyo. PD Dr. Malgorzata Banys-Paluchowski: M.B. has received honoraria for lectures and advisory from Roche, Novartis, Pfizer, pfm, Eli Lilly, Onkowissen, Seagen, AstraZeneca, Eisai, Amgen, Samsung, Canon, MSD, GSK, Daiichi Sankyo, Gilead, Sirius Pintuition, Pierre Fabre, and Exact Sciences; study support from Endomag, Mammotome, Merit Medical, Gilead, Hologic, and Exact Sciences; and travel/congress support from Eli Lilly, Exact Sciences, Pierre Fabre, Pfizer, Daiichi Sankyo, and Roche. Dr. Med. Ingo Bauerfeind, honoraria for lectures: Pfizer, Roche, and Seagen. Prof. Dr. Med. Jens-Uwe Blohmer, honoraria for advisory boards and lectures: AstraZeneca, Daiichi Sankyo, Eisai, Gilead, Lilly, MSD, Novartis, Pfizer, Roche, and Seagen. Prof. Dr. Med. Wilfried Budach, lecture: Merck, BMS, Jörg Eickeler Veranstaltungen, medpublico GmbH, and BVDST. Prof. Dr. Med. Peter Dall, honoraria for lectures and advisory boards: Novartis, Pierre Fabre, Gilead, MSD, Daiichi Sankyo, Lilly, AstraZeneca, Pfizer, and Roche. Prof. Dr. Nina Ditsch, advisory boards and speakers bureaus advisory boards and speakers bureaus: AstraZeneca, Aurikamed, BGGF, Daiichi Sankyo, Elsevier Verlag, ESO, Exact Sciences, Gilead, GSK, if-Kongress, KelCon, Leopoldina Schweinfurt, Lilly, Lukon, Molecular Health, MSD, Novartis, Onkowissen, Pfizer, RG-Ärztefortbildungen, Roche, and Seagen. Prof. Dr. Med. Eva Maria Fallenberg, research grant: DFG; speaker honorarium: GE Healthcare, Bayer Healthcare, Guerbet, Siemens, BD, Roche, EUSOBI, ESOR, ESMO. Prof. Dr. Med. Peter A. Fasching, advisory board: Pfizer, Novartis, Roche, Daiichi Sankyo, Eisai, AstraZeneca, Lilly, MSD, Seagen, Agendia, Pierre Fabre, Sanofi-Aventis, and Gilead Science; lecture: Pfizer, Novartis, Roche, Daiichi Sankyo, Eisai, AstraZeneca, Lilly, MSD, Seagen, and Gilead Sciences; and other: Onkowissen, art tempi. Prof. Dr. Med. Tanja N. Fehm, Onkowissen. Prof. Dr. Med. Michael Friedrich, advisory board: Gilead Sciences; other honoraria: Roche and MSD. Prof. Dr. Med. Bernd Gerber, lecture honoraria: Roche, AstraZeneca, Seagen, Novartis, Pfizer, and MedConcept; and others: Pfizer. PD Dr. Med. Oleg Gluz, honoraria for lectures and/or consulting: Amgen, AstraZeneca, Daiichi Sankyo, Gilead Science, Lilly, MSD, Novartis, Pfizer, Roche, Seagen, Exact Sciences, and Agendia; and minority share holder: Westdeutsche Studiengruppe (WSG)mmc1. Prof. Dr. Med. Nadia Harbeck, honoraria for lectures and/or consulting: Amgen, AstraZeneca, Daiichi Sankyo, Gilead, Lilly, MSD, Novartis, Pierre Fabre, Pfizer, Roche, Sandoz, Sanofi, Seagen, Viatris, and Zuellig Pharma; minority share holder: Westdeutsche Studiengruppe (WSG). Prof. Dr. Med. Andreas Hartkopf, honoraria for consulting and speaking engagements from AstraZeneca, Agendia, Amgen, Clovis, Daiichi Sankyo, Eisai, Exact Science, Gilead, GSK, Hexal, Lilly, MSD, Novartis, Onkowissen, Pfizer, Roche, Pierre Fabre, Seagen, Stemline, and Verazyte. Prof. Dr. Med. Jörg Heil, none. Prof. Dr. Med. Jens Huober, trial funding: Novartis and Lilly; honoraria for lectures: Lilly, Novartis, Roche, Pfizer, AstraZeneca, MSD, Celgene; AbbVie, Seagen, Gilead, and Daiichi; honoraria for consulting/advisory board: Lilly, Novartis, Roche, Pfizer, AstraZeneca, MSD, AbbVie, Daiichi, and Gilead; and travel grants: Roche, Pfizer, Daiichi, and Gilead. Prof. Dr. Med. Christian Jackisch, advisory board: AstraZeneca, Novartis, Lilly, Gilead, Exact Sciences, Pfizer, Roche, GSK, Pierre Fabre, Roche, and Seagen; lecture: Art tempi, AstraZeneca, Lilly, Novartis, Roche, Amgen, Pierre Fabre, Exact Sciences, MSD, Gyn Update, and STREAMED UP. Prof. Dr. Med. Cornelia Kolberg-Liedtke, advisory board: SeaGen, Exact Sciences, Pfizer, Novartis, AstraZeneca, Lilly, SeaGen, Daiichi Sankyo, Agendia, Gilead, and Onkowissen; and lecture: Novartis Ireland, NOGGO, CECOG, PINK, Pfizer, Roche, AstraZeneca, Carl Zeiss Meditec, Lilly, SeaGen, and Daiichi Sankyo; other: Gilead Science and POMME; stockholding: Phaon Scientific and Theraclion SA; and trial Funding: Gilead Science. Prof. Dr. Med. Hans-Heinrich Kreipe, advisory board: Lilly; lecture: AstraZeneca, Roche, Daiichi Sankyo, and Pfizer. PD Dr. David Krug, lecture: Merck Sharp and Dohme, Onkowissen, and Pfizer; research funding: Merck KGaA; and advisory board: Gilead. Prof. Dr. med. Thorsten Kühn, advisory board: Sysmex and NeoDynamics; trial funding: Merit Medical, Endomag, and Mammotome; and lecture: Pfizer. Prof. Dr. Med. Sherko Kümmel, lecture: Roche, Lilly, Exact Sciences, Novartis, Amgen, Daiichi Sankyo, AstraZeneca, Somatex, MSD, Pfizer, pfm medical, Seagen, Gilead Science, and Agendia; other honoraria: Roche, Daiichi Sankyo, and Sonoscape; and advisory board: Lilly, MSD, and Roche. Prof. Dr. Med. Sibylle Loibl, board, advisory board, institutional: AbbVie, Amgen, AstraZeneca, BMS, Celgene, DSI, EirGenix, GSK, Gilead Science, Lilly, Merck, Novartis, Olema, Pfizer, Pierre Fabre, Relay Therapeutics, Puma, Roche, Samsung, Sanofi, and Seagen; invited speaker, institutional: AstraZeneca, DSI, Gilead, Novartis, Pfizer, Pierre Fabre, Roche, and Seagen; invited speaker, personal: Medscape and Stemline-Menarini; trial funding/others: AstraZeneca, AbbVie, Celgene, Daiichi Sankyo, Greenwich Life Sciences, Immunomedics/Gilead, Molecular Health, Novartis, Pfizer, Roche, Seagen, VM Scope Gmbp. Prof. Dr. Med. Diana Lüftner, lecture: Lilly, Roche, MSD, Onkowissen, Novartis, Pfizer, Daiichi Sankyo, Gilead, AstraZeneca, Loreal, and high4md; advisory board: Lilly, Advisory board: Lilly, Roche, MSD, Novartis, Pfizer, Daiichi Sankyo, Gilead, and AstraZeneca; and other: Novartis. Prof. Dr. Med. Michael Patrick Lux: M.P.L. has participated on advisory boards for AstraZeneca, Lilly, MSD, Novartis, Pfizer, Eisai, Gilead, Exact Sciences, Pierre Fabre, Grünenthal, Daiichi Sankyo, PharmaMar, Roche, SamanTree, Sysmex, and Hexal; and has received honoraria for lectures from MSD, Lilly, Roche, Novartis, Pfizer, Exact Sciences, Daiichi Sankyo, Grünenthal, pfm, Gilead, AstraZeneca, and Eisai. Prof. Dr. Med. Nicolai Maass, advisory board: Amgen, AstraZeneca, Clovis, Daiichi Sankyo, GSK, Lilly, MSD, Novartis, Pierre Fabre, Pfizer, Roche, and Seagen; and lecture: AstraZeneca, Daiichi Sankyo, GSK, Lilly, Novartis, Pfizer, and Roche. Prof. Dr. Med. Christoph Mundhenke, advisory board: AstraZeneca, Pfizer, Daiichi Sankyo, Seagen, and Novartis; and lecture: Pfizer and Novartis. Prof. Dr. Med. Toralf Reimer; trial funding: German Cancer Aid and Else Kroener-Fresenius-Stiftung; advisory board: MSD, Novartis, and Myriad; and lecture: Pfizer, Novartis, Roche, and AstraZeneca. Prof. Dr. Med. Kerstin Rhiem, lecture: AstraZeneca, Amgen, and Roche. Prof. Dr. Med. Achim Rody, advisory board: AstraZeneca, Novartis, Roche, Exact Sciences, Pierre Fabre, Lilly, Seagen, Amgen, and MSD; lecture: Pfizer, Celgene, and Eisai; and trial funding: Eisai. Prof. Dr. Med. Marcus Schmidt: MS reports personal fees from AstraZeneca, BioNTech, Daiichi Sankyo, Eisai, Lilly, MSD, Novartis, Pantarhei Bioscience, Pfizer, Pierre Fabre, Roche, and SeaGen; his institution has received research funding from AstraZeneca, BioNTech, Eisai, Genentech, German Breast Group, Novartis, Palleos, Pantarhei Bioscience, Pierre Fabre, and SeaGen. In addition, he has a patent for EP 2390370 B1 and a patent for EP 2951317 B1 issued. Prof. Dr. Med. Andreas Schneeweiss, lecture: Amgen, AstraZeneca, Aurikamed, Clinsol, ConnectMedica, Gilead Science, GSK, I-Med, Lilly, MSD, NanoString, Novartis, Onkowissen, Promedicis, Pfizer, Pierre Fabre, Roche, Seagen, and STREAMED UP; and other: Thieme. Prof. Dr. Med. Florian Schütz, lecture: Amgen, AstraZeneca, Daiichi Sankyo, Eisai, Exact Sciences, Gilead, Pfizer, MSD, Novartis, Onkowissen, and Roche Pharma; and advisory board: Lilly, MSD, and Atheneum Partners; and travel expenses: Lilly, Daiichi Sankyo, and Amgen. Prof. Dr. Med. Hans-Peter Sinn, advisory board: Exact Sciences and Daiichi Sankyo; lecture: AstraZeneca; and trial Funding: AstraZeneca. Prof. Dr. Med. Christine Solbach, lecture: DiaLog Service GmbH, Jörg Eickeler, Pfizer, MedConcept, Medicultus, GBG, Dt. Röntgengesellschaft, BVF Akademie, LÄK Hessen Akademie, Meet the Expert Academy; advisory board: MSD and Roche. Prof. Dr. Med. Erich-Franz Solomayer, Roche, Amgen, Celgen, Tesaro, AstraZeneca, Pfizer, Storz, Erbe, Gedeon Richter, Eisai, Medac, MSD, Vifor, Teva, Ethikon, Johnson & Johnson, Daiichi Sankyo, Gilead, Exact Sciences, GSK, and Pierre Fabre. Prof. Dr. Med. Elmar Stickeler, advisory boards: Gilead, Iomedico, Lilly, MSD, and Seagen; and lecture: Pfizer, Bsh Düsseldorf, Gilead, Iomedico, PharmaMar, Onkowissen, and Roche. Prof. Dr. Med. Christoph Thomssen, compensation for advisory boards, lectures or publications: Amgen, AstraZeneca, Aurikamed, Daiichi Sankyo, Forum Sanitas, Gilead, Jörg Eickeler, Hexal, Lilly, Medupdate, MSD, NanoString, Novartis, Onkowissen, Pfizer, Roche, Seagen, and Vifor. Prof. Dr. Med. Michael Untch: M. U. has received honoraria for lectures and consulting or advisory role from AstraZeneca, Art tempi, Amgen, Daiichi Sankyo, Lilly, Roche, Pfizer, MSD Oncology, Pierre Fabre, Sanofi-Aventis, Myriad, Seagen, Novartis, Gilead, Stemline, Genzyme, Agendia, Onkowissen, Eisai; all honoraria and fees to the employer/institution. Prof. Dr. Isabell Witzel, lecture: Daiichi Sankyo, Pfizer, Roche, MSD, Lilly, Seagen, AstraZeneca, and Gilead; other: Onkowissen. Prof. Dr. Med. Achim Wöckel; advisory board: Amgen, AstraZeneca, Aurikamed, Celgene, Eisai, Lilly, Novartis, Pfizer, Roche, Tesaro, Sirtex, MSD, Genomic Health, Pierre Fabre, Clovis, and Organon. PD. Dr. Rachel Würstlein, Agendia, Amgen, Aristo, AstraZeneca, Aurikamed, Celgene, Clinsol, Clovis Oncology, Daiichi Sankyo, Eisai, Exact Sciences, FOMF, Gilead, Glaxo Smith Kline, Hexal, Lilly, MCI, medconcept, Medstrom Medical, MSD, Mundipharma, Mylan, NanoString, Novartis, Odonate, Paxman, Palleos, Pfizer, Pierre Fabre, PINK, Pomme-med, Puma Biotechnology, Riemser, Roche, Sandoz/Hexal, Sanofi Genzyme, Seattle Genetics/Seagen, Stemline, Tesaro Bio, Teva, Veracyte, and Viatris. Prof. Dr. Med. Volkmar Müller: VM received speaker honoraria from Amgen, AstraZeneca, Daiichi Sankyo, Eisai, Pfizer, MSD, Novartis, Roche, Teva, Seattle Genetics, Genomic Health, Hexal, Roche, Pierre Fabre, Clinsol, Daiichi Sankyo, Eisai, Lilly, Tesaro, Seattle Genetics, and Nektar; institutional research support from Novartis, Roche, Seattle Genetics, and Genentech; and travel grants: Roche, Pfizer, and Daiichi Sankyo. Prof. Dr. Med. Wolfgang Janni, lecture: Amgen, AstraZeneca, Daiichi Sankyo, Lilly, MSD, Novartis, Pfizer, Roche, Seagen, and Gilead Science; trial Funding: Amgen, AstraZeneca, Lilly, Novartis, and Roche. Prof. Dr. Tjoung-Won Park-Simon, honoraria for lectures and/or consulting: Roche, AstraZeneca, GSK, Pfizer, Lilly, MSD, Exact Sciences, Daiichi Sankyo, Seagen, Novartis, Gilead Science, NCO, Onkowissen, Exact Sciences, and Seagen; and travel compensation: Roche, AstraZeneca, and Pfizer., (© 2023 S. Karger AG, Basel.)

Background: In the PAOLA-1/ENGOT-ov25 primary analysis, maintenance olaparib plus bevacizumab demonstrated a significant progression-free survival (PFS) benefit in newly diagnosed advanced ovarian cancer patients in clinical response after first-line platinum-based chemotherapy plus bevacizumab, irrespective of surgical status. Prespecified, exploratory analyses by molecular biomarker status showed substantial benefit in patients with a BRCA1/BRCA2 mutation (BRCAm) or homologous recombination deficiency (HRD; BRCAm and/or genomic instability). We report the prespecified final overall survival (OS) analysis, including analyses by HRD status., Patients and Methods: Patients were randomized 2 : 1 to olaparib (300 mg twice daily; up to 24 months) plus bevacizumab (15 mg/kg every 3 weeks; 15 months total) or placebo plus bevacizumab. Analysis of OS, a key secondary endpoint in hierarchical testing, was planned for ∼60% maturity or 3 years after the primary analysis., Results: After median follow-up of 61.7 and 61.9 months in the olaparib and placebo arms, respectively, median OS was 56.5 versus 51.6 months in the intention-to-treat population [hazard ratio (HR) 0.92, 95% confidence interval (CI) 0.76-1.12; P = 0.4118]. Subsequent poly(ADP-ribose) polymerase inhibitor therapy was received by 105 (19.6%) olaparib patients versus 123 (45.7%) placebo patients. In the HRD-positive population, OS was longer with olaparib plus bevacizumab (HR 0.62, 95% CI 0.45-0.85; 5-year OS rate, 65.5% versus 48.4%); at 5 years, updated PFS also showed a higher proportion of olaparib plus bevacizumab patients without relapse (HR 0.41, 95% CI 0.32-0.54; 5-year PFS rate, 46.1% versus 19.2%). Myelodysplastic syndrome, acute myeloid leukemia, aplastic anemia, and new primary malignancy incidence remained low and balanced between arms., Conclusions: Olaparib plus bevacizumab provided clinically meaningful OS improvement for first-line patients with HRD-positive ovarian cancer. These prespecified exploratory analyses demonstrated improvement despite a high proportion of patients in the placebo arm receiving poly(ADP-ribose) polymerase inhibitors after progression, confirming the combination as one of the standards of care in this setting with the potential to enhance cure., Competing Interests: Disclosure IRC reports honoraria (personal) from AbbVie, Agenus, Advaxis, Bristol Myers Squibb (BMS), PharmaMar, Genmab, Pfizer, AstraZeneca, Roche, GlaxoSmithKline (GSK), Merck Sharp & Dohme (MSD), Deciphera, Mersana, Merck Sereno, Novartis, Amgen, Tesaro, and Clovis; honoraria (institution) from GSK, MSD, Roche, and BMS; advisory/consulting fees from AbbVie, Agenus, Advaxis, BMS, PharmaMar, Genmab, Pfizer, AstraZeneca, Roche/Genentech, GSK, MSD, Deciphera, Mersana, Merck Sereno, Novartis, Amgen, Tesaro, and Clovis; research grant/funding (self) from MSD, Roche, and BMS; research grant/funding (institution) from MSD, Roche, BMS, Novartis, AstraZeneca, and Merck Sereno; and travel support from Roche, AstraZeneca, and GSK. AL reports grants from AstraZeneca and Sanofi; consulting fees from Seattle Genetics; honoraria/reimbursement and advisory board fees from AstraZeneca; advisory board fees or continuing medical education from Ability Pharma, Biocad, Clovis Oncology, GSK, Medscape, Merck Serono, MSD, TouchCongress, and Zentalis; support for attending meetings and/or travel from AstraZeneca, Clovis Oncology, GSK, and Roche; and participation on a data safety monitoring board or advisory board for ARIEL4 and TROPHIMMUNE. SP reports honoraria from AstraZeneca, Roche, MSD, Pfizer, Tesaro, Clovis Oncology, GSK, and PharmaMar; and research funding (institution) from Roche, MSD, AstraZeneca, and Pfizer. AGM reports advisory/consultancy fees (personal) from Alkermes, Amgen, AstraZeneca, Clovis Oncology, Eisai, Genmab, GSK, Hedera Dx, Illumina, ImmunoGen, MSD, Macrogenics, Mersana, Novartis, Oncoinvent, PharmaMar, Roche, Regeneron, Sotio, and Sutro; speaker bureau fees (personal) from AstraZeneca, Roche, GSK, MSD, Novocure, Takeda, Zai Lab, and Clovis; research grant/funding (institution) from Roche, Novartis, GSK, and Aravive; and steering committee member (personal) for MSD. CM reports honoraria/consulting fees (personal) from Roche, Novartis, Amgen, MSD, PharmaMar, AstraZeneca, GSK, and Seagen; participation on an advisory board from Roche, Novartis, Amgen, MSD, PharmaMar, AstraZeneca, GSK, and Seagen; and travel expenses from Roche and AstraZeneca. SN reports honoraria (self) from AstraZeneca, Chugai, Mochida, MSD, Takeda, and Terumo; and research grant (self) from AstraZeneca. IV reports consulting fees from Agenus, Akesobio, AstraZeneca, BMS, Deciphera Pharmaceuticals, Eisai, Elevar Therapeutics, F. Hoffmann-La Roche, Genmab, GSK, Immunogen, Jazzpharma, Karyopharm, Mersana, MSD, Novocure, Novartis, Oncoinvent, OncXerna, Sanofi, Seagen, Sotio, Verastem Oncology, and Zentalis; contracted research funding (via KULeuven) from Oncoinvent AS; corporate sponsored research funding from Amgen and Roche; and accommodation and travel expenses from Karyopharm. NC reports research grants from AstraZeneca, PharmaMar, and Roche; honoraria for lectures from AstraZeneca, Tesaro, Novartis, Clovis Oncology, MSD, GSK, and Eisai; honoraria for advisory boards from Roche, PharmaMar, AstraZeneca, Clovis Oncology, MSD, GSK, Tesaro, Pfizer, BIOCAD, ImmunoGen, Mersana Therapeutics, Eisai, and OncXerna Therapeutics; and is a steering committee member on ESMO clinical guidelines and a scientific committee chair for Acto Onlus. JM reports honoraria from AstraZeneca and GSK. FS reports honoraria from AstraZeneca, GSK Tesaro, MSD, Sandoz (Novartis), and Clovis Oncology; and institutional financial support from Roche, GSK Tesaro, AstraZeneca, Immunogen, MSD, Incyte, and Agenus. JS reports grants or contracts from Roche Pharma, AstraZeneca, Bayer, Clovis, GSK, Lilly, Tesaro, consulting fees from Tesaro, Merck, Pfizer, PharmaMar, Clovis Oncology, AstraZeneca, Roche Pharma, GSK, MSD, Eisai, Novocure, Oncoinvent, payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Tesaro, GSK, PharmaMar, AstraZeneca, Clovis, Bayer, Roche, PharmaMar, Vifor Pharma, Hexal AG, Novartis Pharma. DL reports consultancy fees (personal) from AstraZeneca, Clovis Oncology, Genmab, GSK, Immunogen, MSD, PharmaMar, Novartis, and Seagen; membership on an advisory board (personal) from AstraZeneca, Clovis Oncology, Corcept, Genmab, GSK, Immunogen, MSD, Oncoinvest, PharmaMar, Seagen, and Sutro; research funding (institutional) from AstraZeneca, Clovis Oncology, Genmab, GSK, Immunogen, Incyte, MSD, Novartis, PharmaMar, Roche, and Seagen; and travel support from Roche, PharmaMar, AstraZeneca, Clovis Oncology, and GSK. EMGA reports consulting fees from AstraZeneca–MSD, Clovis Oncology, GSK–Tesaro, PharmaMar, and Roche; speaker bureau/expert testimony honorarium from AstraZeneca–MSD, PharmaMar, Roche, GSK–Tesaro, and Clovis Oncology; and travel support from Roche, GSK–Tesaro, and Baxter. GB reports consulting or advisory board roles for AstraZeneca, Roche, and GSK; and has received funding for medical conferences from AstraZeneca, Roche, and GSK. CLP reports advisory/consultancy honoraria from Pfizer, AstraZeneca, Roche, and Daiichi–Sanko; and other travel/accommodation/medical congress expenses from Roche, Novartis, Pfizer, Pierre Fabre, and MSD. PB reports honoraria from Roche, AstraZeneca, and GSK; and congress and travel support from GSK and PharmaMar. AL reports advisory board fees from AstraZeneca, MSD, and Tesaro; speaker honoraria from Clovis Oncology and Roche; and participation in a medical congress for Novartis, Pfizer, MSD, Lilly, and Roche. AB reports honoraria for lectures and advisory boards from AstraZeneca, Roche, and Tesaro. JM reports advisory board fees (personal) from Daiichi Sankyo, Gilead, and Eli Lilly; and non-financial traveling facilities from Pfizer. AEB reports advisory board fees from AstraZeneca, MSD, and GSK; speaker honoraria from AstraZeneca and Olympus; and participation in a medical congress for PharmaMar and AstraZeneca. MR reports advisory board fees (personal) from AstraZeneca, GSK, and Immunocore; advisory board fees and research grant (personal/institution) from MSD; and research grant (institution) from BMS. TWPS reports honoraria (advisory role, expert testimony and lectures, participation in clinical trials, other financial relationships, e.g. travel) from AstraZeneca, Daiichi-Sankyo, Exact Sciences, Gilead, GSK, Lilly, MSD, NCO, Novartis, Pfizer, Roche, and Seagen. CD reports participation on a data safety monitoring board or advisory board for MSD, Eisai, and AstraZeneca. DD reports consulting or advisory roles (personal) for AstraZeneca, GSK/Tesaro, Roche, Eisai Germany, and MSD Oncology; travel expenses from AstraZeneca; and honoraria from Roche, AstraZeneca, GSK/Tesaro, MSD, Intuitive Surgical, and KLS Martin. BY reports consulting fees (personal) from MSD, AstraZeneca, GSK–Tesaro, Bayer, Roche–Genentech, ECS Progastrin, Novartis, LEK, Amgen, Clovis Oncology, Merck Serono, BMS, SEAGEN, and Myriad. EPL reports lecture fees, speaker’s bureau fees, and travel support from AstraZeneca, Tesaro, and Roche; lecture fees from Clovis Oncology, Incyte, and Pfizer; and is employed by ARCAGY Research. PH reports honoraria from AstraZeneca, Roche, Clovis Oncology, Stryker, MSD Oncology, Zai Lab, Lilly, Sotio, Eisai, and GSK; consulting/advisory roles from AstraZeneca, Roche, Tesaro, Merck, GSK, Clovis Oncology, and Immunogen; and research funding (institution) from AstraZeneca, Roche, Genmab, GSK, Immunogen, and Clovis Oncology. All other authors have declared no conflicts of interest., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Breast cancer (BC) patients with a germline CHEK2 c.1100delC variant have an increased risk of contralateral BC (CBC) and worse BC-specific survival (BCSS) compared to non-carriers., Aim: To assessed the associations of CHEK2 c.1100delC, radiotherapy, and systemic treatment with CBC risk and BCSS., Methods: Analyses were based on 82,701 women diagnosed with a first primary invasive BC including 963 CHEK2 c.1100delC carriers; median follow-up was 9.1 years. Differential associations with treatment by CHEK2 c.1100delC status were tested by including interaction terms in a multivariable Cox regression model. A multi-state model was used for further insight into the relation between CHEK2 c.1100delC status, treatment, CBC risk and death., Results: There was no evidence for differential associations of therapy with CBC risk by CHEK2 c.1100delC status. The strongest association with reduced CBC risk was observed for the combination of chemotherapy and endocrine therapy [HR (95% CI): 0.66 (0.55-0.78)]. No association was observed with radiotherapy. Results from the multi-state model showed shorter BCSS for CHEK2 c.1100delC carriers versus non-carriers also after accounting for CBC occurrence [HR (95% CI): 1.30 (1.09-1.56)]., Conclusion: Systemic therapy was associated with reduced CBC risk irrespective of CHEK2 c.1100delC status. Moreover, CHEK2 c.1100delC carriers had shorter BCSS, which appears not to be fully explained by their CBC risk., (© 2023 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Background: Up to 30% of metastatic breast cancer (BC) patients develop brain metastases (BM). Prognosis of patients with BM is poor and long-term survival is rare. Identification of factors associated with long-term survival is important for improving treatment modalities., Patients and Methods: A total of 2889 patients of the national registry for BM in BC (BMBC) were available for this analysis. Long-term survival was defined as overall survival (OS) in the upper third of the failure curve resulting in a cut-off of 15 months. A total of 887 patients were categorized as long-term survivors., Results: Long-term survivors compared to other patients were younger at BC and BM diagnosis (median 48 versus 54 years and 53 versus 59 years), more often had HER2-positive tumors (59.1% versus 36.3%), less frequently luminal-like (29.1% versus 35.7%) or triple-negative breast cancer (TNBC) (11.9% versus 28.1%), showed better Eastern Cooperative Oncology Group (ECOG) performance status (PS) at the time of BM diagnosis (ECOG 0-1, 76.9% versus 51.0%), higher pathological complete remission rates after neoadjuvant chemotherapy (21.6% versus 13.7%) and lower number of BM (n = 1, BM 40.9% versus 25.4%; n = 2-3, BM 26.5% versus 26.7%; n ≥4, BM 32.6% versus 47.9%) (P < 0.001). Long-term survivors had leptomeningeal metastases (10.4% versus 17.5%) and extracranial metastases (ECM, 73.6% versus 82.5%) less frequently, and asymptomatic BM more often at the time of BM diagnosis (26.5% versus 20.1%), (P < 0.001). Median OS in long-term survivors was about two times higher than the cut-off of 15 months: 30.9 months [interquartile range (IQR) 30.3] overall, 33.9 months (IQR 37.1) in HER2-positive, 26.9 months (IQR 22.0) in luminal-like and 26.5 months (IQR 18.2) in TNBC patients., Conclusions: In our analysis, long-term survival of BC patients with BM was associated with better ECOG PS, younger age, HER2-positive subtype, lower number of BM and less extended visceral metastases. Patients with these clinical features might be more eligible for extended local brain and systemic treatment., Competing Interests: Disclosure IW received speaker’s honoraria from Astra Zeneca, Merck, Pfizer, Roche, Daiichi-Sankyo, Seagen, Gilead and Novartis. KL received speaker’s honoraria from Roche, Novartis, Pfizer, Exact Sciences, MSD, Eisai, Lilly, Seagen, AstraZeneca and Daiichy Sankyo. MS has received personal fees from AstraZeneca, BioNTech, Daiichi-Sankyo, Eisai, Lilly, MSD, Novartis, Pantarhei Bioscience, Pfizer, Pierre Fabre, Roche and Seagen. His institution has received research funding from AstraZeneca, BioNTech, Eisai, Genentech, German Breast Group, Novartis, Palleos, Pantarhei Bioscience, Pierre Fabre and Seagen. In addition, he has a patent for EP 2390370 B1 and a patent for EP 2951317 B1 issued. SL reports grants, non-financial support and other from Daiichi-Sankyo, during the conduct of the study; grants and other from Abbvie, other from Amgen, grants and other from AstraZeneca, other from BMS, grants and other from Celgene, other from Eirgenix, other from Eisai Europe Ltd, other from GSK, grants, non-financial support and other from Immunomedics/Gilead, other from Lilly, other from Merck, grants from Molecular Health, grants, non-financial support and other from Novartis, grants, non-financial support and other from Pfizer, other from Pierre Fabre, other from Relay Therapeutics, grants, non-financial support and other from Roche, other from Sanofi, non-financial support and other from Seagen, other from Olema Pharmaceutics, outside the submitted work; In addition, SL has a patent EP14153692.0 pending, a patent EP21152186.9 pending, a patent EP15702464.7 issued, a patent EP19808852.8 pending and a patent Digital Ki67 Evaluator with royalties paid. CD reports advisory role for MSD Oncology, Daiichi-Sankyo, Molecular Health, AstraZeneca, Roche and Lilly; CD received research funding from Myriad Genetics, Roche and German Breast Group; CD owns following patents: VMScope digital pathology software, Patent WO2020109570A1, Patent WO2015114146A1, Patent WO2010076322A1. MT received personal fees from Agendia, Amgen, Art tempi, AstraZeneca, Aurikamed, Celgene, Daiichi-Sankyo, Eisai, Exact Sciences, Gilead Science, Grünenthal, GSK, Hexal, Lilly, MSD, Novartis, Onkowissen, Organon, Pfizer, Pierre Fabre, Roche, Seagen, Servier, Streamd Up!, Viatris, Vifor, trial funding from Exact Science and institutional trial honoraria from AstraZeneca, Celgene, Novartis, Roche. VM received speaker honoraria from Amgen, Astra Zeneca, Daiichi-Sankyo, Eisai, GSK, Pfizer, MSD, Medac, Novartis, Roche, Teva, Seagen, Onkowissen, high5 Oncology, Medscape, Gilead and Pierre Fabre; consultancy honoraria from Hexal, Roche, Pierre Fabre, Amgen, ClinSol, Novartis, MSD, Daiichi-Sankyo, Eisai, Lilly, Sanofi, Seagen and Gilead; Institutional research support from Novartis, Roche, Seagen, Genentech; travel grants: Roche, Pfizer, Daiichi-Sankyo, Gilead. RW received support for advisory, consultancy, speaker and travel grants from Agendia, Amgen, Aristo, AstraZeneca, Boeringer Ingelheim, Carl Zeiss, Celgene, Clinsol, Clovis Oncology, Daiichi-Sankyo, Eisai, Exact Sciences, Genomic Health, Gilead, 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, Stemline, Tesaro Bio, Teva, Veracyte and Viatris. TD received Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Novartis, IOMEDICO and participated on a Data Safety Monitoring Board or Advisory Board for Novartis, IOMEDICO. All other authors have declared no conflicts of interest., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Evidence linking coding germline variants in breast cancer (BC)-susceptibility genes other than BRCA1, BRCA2, and CHEK2 with contralateral breast cancer (CBC) risk and breast cancer-specific survival (BCSS) is scarce. The aim of this study was to assess the association of protein-truncating variants (PTVs) and rare missense variants (MSVs) in nine known (ATM, BARD1, BRCA1, BRCA2, CHEK2, PALB2, RAD51C, RAD51D, and TP53) and 25 suspected BC-susceptibility genes with CBC risk and BCSS. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated with Cox regression models. Analyses included 34,401 women of European ancestry diagnosed with BC, including 676 CBCs and 3,449 BC deaths; the median follow-up was 10.9 years. Subtype analyses were based on estrogen receptor (ER) status of the first BC. Combined PTVs and pathogenic/likely pathogenic MSVs in BRCA1, BRCA2, and TP53 and PTVs in CHEK2 and PALB2 were associated with increased CBC risk [HRs (95% CIs): 2.88 (1.70-4.87), 2.31 (1.39-3.85), 8.29 (2.53-27.21), 2.25 (1.55-3.27), and 2.67 (1.33-5.35), respectively]. The strongest evidence of association with BCSS was for PTVs and pathogenic/likely pathogenic MSVs in BRCA2 (ER-positive BC) and TP53 and PTVs in CHEK2 [HRs (95% CIs): 1.53 (1.13-2.07), 2.08 (0.95-4.57), and 1.39 (1.13-1.72), respectively, after adjusting for tumor characteristics and treatment]. HRs were essentially unchanged when censoring for CBC, suggesting that these associations are not completely explained by increased CBC risk, tumor characteristics, or treatment. There was limited evidence of associations of PTVs and/or rare MSVs with CBC risk or BCSS for the 25 suspected BC genes. The CBC findings are relevant to treatment decisions, follow-up, and screening after BC diagnosis., Competing Interests: Declaration of interests B.D. is a stockholder of Roche, Vaccitech and EQRx. P.A.F. conducts research funded by Amgen, Novartis, and Pfizer outside the submitted work. He received honoraria from Roche, Novartis, and Pfizer outside the submitted work. D.F.E. is an associate editor at The American Journal of Human Genetics (AJHG)., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose: To compare standard versus extended duration of bevacizumab treatment in combination with front-line chemotherapy in women with newly diagnosed stage IIB-IV ovarian cancer., Methods: In this multicenter, open-label, randomized phase III trial (ClinicalTrials.gov identifier: NCT01462890), patients with newly diagnosed International Federation of Gynecology and Obstetrics stage IIB-IV epithelial ovarian, fallopian tube, or peritoneal cancer underwent primary cytoreductive surgery followed by six cycles of chemotherapy (paclitaxel 175 mg/m 2 plus carboplatin area under the curve 5 once every 3 weeks) and bevacizumab (15 mg/kg once every 3 weeks). Patients were randomly assigned 1:1 to receive bevacizumab for either 15 or 30 months, stratified by International Federation of Gynecology and Obstetrics stage/residual tumor. The primary end point was investigator-assessed progression-free survival (PFS) according to RECIST version 1.1. Secondary end points included overall survival (OS), safety, and tolerability., Results: Between November 11, 2011, and August 6, 2013, 927 women were randomly assigned. There was no difference in PFS between treatment arms (hazard ratio, 0.99; 95% CI, 0.85 to 1.15; unstratified log-rank P = .90). Median PFS was 24.2 versus 26.0 months with standard versus extended duration of bevacizumab, respectively; restricted mean PFS was 39.5 versus 39.3 months, respectively. There was no OS difference between treatment arms (hazard ratio, 1.04; 95% CI, 0.87 to 1.23; P = .68). Serious/nonserious adverse events of special interest occurred in 29% versus 34% of patients in the standard versus experimental arms, respectively, and were consistent with the known safety profile of standard bevacizumab., Conclusion: Longer treatment duration with bevacizumab for up to 30 months did not improve PFS or OS in patients with primary epithelial ovarian, fallopian tube, or peritoneal cancer. A bevacizumab treatment duration of 15 months remains the standard of care.

Purpose: The identification of a robust IHC marker to predict the response to antiangiogenic bevacizumab in ovarian cancer is of high clinical interest. VEGF-A, the molecular target of bevacizumab, is expressed as multiple isoforms with pro- or antiangiogenic properties, of which VEGF-A165b is the most dominant antiangiogenic isoform. The balance of VEGF-A isoforms is closely related to the angiogenic capacity of a tumor and may define its vulnerability to antiangiogenic therapy. We investigated whether the expression of VEGF-A165b could be related to the effect of bevacizumab in advanced ovarian cancer patients., Experimental Design: Formalin-fixed paraffin-embedded tissues from 413 patients of the ICON7 multicenter phase III trial, treated with standard platinum-based chemotherapy with or without bevacizumab, were probed for VEGF-A165b expression by IHC., Results: In patients with low VEGF-A165b expression, the addition of bevacizumab to standard platinum-based chemotherapy significantly improved progression-free (HR: 0.727; 95% CI, 0.538-0.984; P = 0.039) and overall survival (HR: 0.662; 95% CI, 0.458-0.958; P = 0.029). Multivariate analysis showed that the addition of bevacizumab in low VEGF-A165b-expressing patients conferred significant improvements in progression-free survival (HR: 0.610; 95% CI, 0.446-0.834; P = 0.002) and overall survival (HR: 0.527; 95% CI, 0.359-0.775; P = 0.001), independently from established risk factors., Conclusions: We demonstrate for the first time that bevacizumab may differentially improve the prognosis of advanced ovarian cancer patients with low expression of VEGF-A165b, an antiangiogenic VEGF-A splice variant. We envision that this novel biomarker could be implemented into routine diagnostics and may have direct clinical implications for guiding bevacizumab-related treatment decisions in advanced ovarian cancer patients., (©2022 American Association for Cancer Research.)

Background: In the SOLO2 trial (ENGOT Ov-21; NCT01874353), maintenance olaparib in patients with platinum-sensitive relapsed ovarian cancer (PSROC) and BRCA mutation significantly improved progression-free survival (PFS) and prolonged overall survival (OS). Following disease progression on olaparib, efficacy of subsequent chemotherapy remains unknown., Patients and Methods: We conducted a post-hoc hypothesis-generating analysis of SOLO2 data to determine the efficacy of different chemotherapy regimens following RECIST disease progression in patients who received olaparib or placebo. We evaluated time to second progression (TTSP) calculated from the date of RECIST progression to the next progression/death., Results: The study population comprised 147 patients who received chemotherapy as their first subsequent treatment after RECIST progression. Of these, 69 (47%) and 78 (53%) were originally randomized to placebo and olaparib arms, respectively. In the placebo-treated cohort, 27/69 and 42/69 received non-platinum and platinum-based chemotherapy, respectively, compared with 24/78 and 54/78, respectively, in the olaparib-treated cohort. Among patients treated with chemotherapy (N = 147), TTSP was significantly longer in the placebo than in the olaparib arm: 12.1 versus 6.9 months [hazard ratio (HR) 2.17, 95% confidence interval (CI) 1.47-3.19]. Similar result was obtained on multivariable analysis adjusting for prognostic factors at RECIST progression (HR 2.13, 95% CI 1.41-3.22). Among patients treated with platinum-based chemotherapy (n = 96), TTSP was significantly longer in the placebo arm: 14.3 versus 7.0 months (HR 2.89, 95% CI 1.73-4.82). Conversely, among patients treated with non-platinum-based chemotherapy (n = 51), the TTSP was comparable in the placebo and olaparib arms: 8.3 versus 6.0 months (HR 1.58, 95% CI 0.86-2.90)., Conclusions: Following progression from maintenance olaparib in the recurrent setting, the efficacy of platinum-based subsequent chemotherapy seems to be reduced in BRCA1/2-mutated patients with PSROC compared to patients not previously receiving poly (ADP-ribose) polymerase inhibitors (PARPi). The optimal strategy for patients who relapse after PARPi is an area of ongoing research., Competing Interests: Disclosure JSF reports personal fees from Roche Genentech, personal fees and non-financial support from Seattle Genetics, Novartis, Pfizer, Lilly, Novartis, GSK, Clovis oncology, AstraZeneca, Daiichi Sankyo, Gilead, MSD, Pierre Fabre, and Amgen, outside the submitted work. PP reports non-financial support from GSK, AstraZeneca, Clovis Oncology outside the submitted work. JAL reports personal fees from Pfizer, AstraZeneca, GSK, MSD, Clovis Oncology, Eisai, Bristol Myers Squibb, Artios Pharma, VBL Therapeutics, Neopharm, outside the submitted work. RTP reports personal fees from AbbVie, AstraZeneca, Eisai, Genentech / Roche, GSK Inc., Merck & Co, Sutro Biopharma, Vascular Biogenics Ltd, outside the submitted work. SP reports personal fees from, AstraZeneca, MSD; ROCHE, Clovis, GSK, Pfizer, PharmaMar, outside the submitted work. NC reports personal fees from AstraZeneca, Esai, Genentech, GSK, Merck, Pfizer, Regeneron pharmaceutical, outside the submitted work. TWPS reports personal fee from AstraZeneca, Tesaro, GSK, outside the submitted work. GSS has received grant from Agendia, AstraZeneca, Merck, Novartis, Roche, Seagen, outside the submitted work. CKL reports personal fee from AstraZeneca, Amgen, Takeda, Boehringer Ingelheim, Pfizer, Yuhan, Merck KGA, Roche, MSD, outside the submitted work. EPL reports grants and personal fees from AstraZeneca, Merck, GSK, Roche, Incyte, ARCAGY Research, outside the submitted work. All other authors have declared no conflicts of interest., (Copyright © 2022. Published by Elsevier Ltd.)

The recommendations of the AGO Breast Committee on the surgical therapy of breast cancer were last updated in March 2022 (www.ago-online.de). Since surgical therapy is one of several partial steps in the treatment of breast cancer, extensive diagnostic and oncological expertise of a breast surgeon and good interdisciplinary cooperation with diagnostic radiologists is of great importance. The most important changes concern localization techniques, resection margins, axillary management in the neoadjuvant setting and the evaluation of the meshes in reconstructive surgery. Based on meta-analyses of randomized studies, the level of recommendation of an intraoperative breast ultrasound for the localization of non-palpable lesions was elevated to "++". Thus, the technique is considered to be equivalent to wire localization, provided that it is a lesion which can be well represented by sonography, the surgeon has extensive experience in breast ultrasound and has access to a suitable ultrasound device during the operation. In invasive breast cancer, the aim is to reach negative resection margins ("no tumor on ink"), regardless of whether an extensive intraductal component is present or not. Oncoplastic operations can also replace a mastectomy in selected cases due to the large number of existing techniques, and are equivalent to segmental resection in terms of oncological safety at comparable rates of complications. Sentinel node excision is recommended for patients with cN0 status receiving neoadjuvant chemotherapy after completion of chemotherapy. Minimally invasive biopsy is recommended for initially suspect lymph nodes. After neoadjuvant chemotherapy, patients with initially 1 - 3 suspicious lymph nodes and a good response (ycN0) can receive the targeted axillary dissection and the axillary dissection as equivalent options., Competing Interests: Conflict of Interest/Interessenkonflikt Maggie Banys-Paluchowski received fees for lectures and consultancy activities from Roche, Novartis, Pfizer, pfm, Eli Lilly, Onkowissen, Seagen, AstraZeneca, Eisai, AstraZeneca, Amgen, Samsung, MSD, GSK, Daiichi Sankyo, Gilead, Sirius Pintuition, Pierre Fabre and study support from EndoMag, Mammotome, MeritMedical. Marcus Schmidt reports that he received personal fees for lectures and consulting activities from AstraZeneca, BioNTech, Daiichi Sankyo, Eisai, Lilly, MSD, Novartis, Pantarhei Bioscience, Pfizer, Roche and SeaGen, which are not related to this publication. Jens Huober: Research support: Celgene, Novartis, Hexal, Lilly. Lecture activity: Lilly, Novartis, Roche, Pfizer, AstraZeneca, MSD, Celgene; Eisai, Abbvie, Seagen, Gilead. Consultancy: Lilly, Novartis, Roche, Pfizer, Hexal, AstraZeneca, MSD, Celgene, Abbvie. Travel expenses: Roche, Pfizer, Novartis, Celgene, Daiichi Sankyo. Peter Dall: Lecture fees: Novartis, Pfizer, AstraZeneca, Roche, Lilly. Ad Boards: Novartis, Seagen, Daiichi Sankyo, AstraZeneca, Roche, Gilead. David Krug: honoraria from Merck Sharp & Dohme and Pfizer as well as research funding from Merck KGaA. Other authors do not indicate any conflicts of interest./ Maggie Banys-Paluchowski erhielt Honorare für Vorträge und beratende Tätigkeiten von Roche, Novartis, Pfizer, pfm, Eli Lilly, Onkowissen, Seagen, AstraZeneca, Eisai, AstraZeneca, Amgen, Samsung, MSD, GSK, Daiichi Sankyo, Gilead, Sirius Pintuition, Pierre Fabre und Studienunterstützung von EndoMag, Mammotome, MeritMedical. Marcus Schmidt berichtet, persönliche Honorare für Vorträge und Beratungstätigkeiten von AstraZeneca, BioNTech, Daiichi Sankyo, Eisai, Lilly, MSD, Novartis, Pantarhei Bioscience, Pfizer, Roche und SeaGen erhalten zu haben, die nicht im Zusammenhang mit der vorliegenden Publikation stehen. Jens Huober: Forschungsunterstützung: Celgene, Novartis, Hexal, Lilly. Vortragstätigkeit: Lilly, Novartis, Roche, Pfizer, AstraZeneca, MSD, Celgene; Eisai, Abbvie, Seagen, Gilead. Beratertätigkeit: Lilly, Novartis, Roche, Pfizer, Hexal, AstraZeneca, MSD, Celgene, Abbvie. Reisekosten: Roche, Pfizer, Novartis, Celgene, Daiichi Sankyo. Peter Dall: Vortragshonorare: Novartis, Pfizer, AstraZeneca, Roche, Lilly. Ad-Boards: Novartis, Seagen, Daiichi Sankyo, AstraZeneca, Roche, Gilead. David Krug: honoraria from Merck Sharp & Dohme and Pfizer as well as research funding from Merck KGaA. Weitere AutorInnen geben keine Interessenkonflikte an., (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/ ).)