Association between risk-reducing surgeries and survival in young BRCA carriers with breast cancer: an international cohort study
- PMID: 40347973
- DOI: 10.1016/S1470-2045(25)00152-4
Association between risk-reducing surgeries and survival in young BRCA carriers with breast cancer: an international cohort study
Abstract
Background: Little evidence exists on the effect of risk-reducing surgeries in young BRCA carriers with a previous history of breast cancer. We investigated the association between risk-reducing mastectomy (RRM) or risk-reducing salpingo-oophorectomy (RRSO), or both procedures, with survival outcomes in a large global cohort of young BRCA carriers with previous breast cancer.
Methods: The BRCA BCY Collaboration is an international, hospital-based, retrospective cohort study, conducted at 109 centres in five continents, including women harbouring germline BRCA1, BRCA2, or both, pathogenic or likely pathogenic variants and diagnosed with stage I-III invasive breast cancer at the age of 40 years or younger between Jan 1, 2000, and Dec 31, 2020. The primary objectives of the present analysis were to determine the association between RRM or RRSO and overall survival in young BRCA carriers with breast cancer. The primary endpoint was overall survival. This study is registered with ClinicalTrials.gov, NCT03673306.
Findings: Between Jan 1, 2000 and Dec 31, 2020, 5290 patients were included, of whom 3361 (63·5%) patients were BRCA1 pathogenic variant carriers, 2708 (51·2%) had node-negative, and 2421 (45·8%) hormone receptor-positive breast cancer. Of 5290 patients, 2910 (55·0%) underwent RRM, 2782 (52·6%) underwent RRSO. After a median follow-up of 8·2 years (IQR 4·7-12·8), RRM was associated with significantly better overall survival compared with no RRM (adjusted HR [aHR] 0·65, 95% CI 0·53-0·78; 20-year restricted mean overall survival time 17·89 years [95% CI 17·61-18·17] with RRM vs 16·65 years [16·38-16·92] without RRM). RRSO was also associated with significantly better overall survival compared with no RRSO (aHR 0·58, 95% CI 0·48-0·71; 20-year restricted mean overall survival time 17·73 years [95% CI 17·43-18·03] with RRSO vs 16·67 years [16·38-16·96] without RRSO).
Interpretation: In this global cohort of BRCA carriers with previous breast cancer diagnosis at a young age, RRM and RRSO were both associated with a significant improvement in overall survival. These findings provide evidence for a tailored counselling of a unique and high-risk patient population on cancer risk management strategies.
Funding: Italian Association for Cancer Research.
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Conflict of interest statement
Declaration of interests EB reports speakers fees from Eli Lilly and research funding (to their institution) from Gilead, outside the submitted work. ASo reports consulting or advisory roles for Eli Lilly, Novartis, Roche, and Stemline; travel, accommodations, and expenses from Roche and Pfitzer; speakers bureau at Roche, Novartis, Stemline, Progenetics, Gilead, and MSD; and grant support from Novartis, Roche, and Gilead, outside the submitted work. EA reports speakers honoraria from Eli Lilly, AstraZeneca, Bayer, and Abscint; advisory role for AstraZeneca; research grant (to their institution) from Gilead; and meeting or travel grants from Eli Lilly, Daiichi Sankyo, AstraZeneca, Menarini, and Abscint, outside the submitted work. MAF reports honoraria for lectures from Novartis; fiduciary role (unpaid) on the LACOG Digital Health Steering Committee, SBOC Survivorship Committee, and American Society of Clinical Oncology Guidelines Committee; and grant support from Gilead sciences and Resilience, outside the submitted work. RB-M reports honoraria for lectures from AstraZeneca, Roche, and Pfizer; and support for attending meetings from Pfizer, AstraZeneca, and Gilead, outside the submitted work. AK reports honoraria for speakers from AstraZeneca Hong Kong, Chongqing Medical Technology, Roche Hong Kong, AstraZeneca Taiwan, and Merch Sharp & Dohme (Asia); support for attending meetings from Roche Hong Kong, AstraZeneca Hong Kong; and receipt of equipment from Roche Hong Kong, Merch Sharp & Dohme, AstraZeneca, Gilead Sciences, Olema Pharmaceuticals, and IceCure Medical, outside the submitted work. KP reports honoraria for consultations, lectures, training, and clinical trials and payment of conferences fees from AstraZeneca, Novartis, and Eli Lilly; payment for expert testimony from Novartis, AstraZeneca, and MSD; support for attending meetings from Roche, AstraZeneca, and Novartis; participation on boards for Novartis and AstraZeneca; and fiduciary roles for the Polish Society of Clinical Oncology and Breast Cancer Group in the European Organisation for Research and Treatment of Cancer, outside the submitted work. JBal reports speaker honoraria and research (to their institution) from AstraZeneca; grant support from Breast Cancer Research Foundation, USA (BCRF23–203 and BCRF24–203); grant support from Instituto de Salud Carlos III, Spain (ISCIII PI23–01047); support for attending meetings from AstraZeneca and Eli Lilly; and a pending European patent (request submitted), outside the submitted work. ASm reports grant support from Gilead; consulting or advisory roles with Roche, MSD, and J&J; and a patent PCT/EP2022/069583, outside the submitted work. HCFM reports grant support from AstraZeneca, Daiichi-Sanko, Roche-Genentech, Sermonix, Seattle Genetics, and Pfizer, outside the submitted work. AT reports consulting or advisory roles with Lilly, Novartis, Pfizer, MSD, AstraZeneca, Daiichi Sankyo, Gilead, and Menarini Stemline; honoraria for consultations, lectures, training, and clinical trials and payment of conferences fees from Lilly, Novartis, Pfizer, MSD, AstraZeneca, Daiichi Sankyo, Gilead, and Menarini Stemline; support for attending meetings from AstraZeneca, Daiichi Sankyo, and Gilead; and participation on boards for Lilly, Novartis, Pfizer, MSD, AstraZeneca, Daiichi Sankyo, Gilead, and Menarini Stemline, outside the submitted work. CR-J reports honoraria for consultations, lectures, training, and clinical trials and payment of conferences fees from Theramex, Organon, and Astellas; support for attending meetings from Gédéon Richter; and participation on boards from Bayer, Gédéon Richter, and Astellas, outside the submitted work. AF reports honoraria for consultations, lectures, training, and clinical trials and payment of conferences fees from AstraZeneca and MDS; participation on boards for AstraZeneca; fiduciary roles as an honorary president and scientific referent of aBRCAdabra ETS, and Italian advocacy of BRCA carriers, outside the submitted work. SP-S reports consulting or advisory roles with Roche, Summit Therapeutics, Lilly, Novartis, Stemline, Pfizer, Medison, Exact Sciences, AstraZeneca, Gilead, and MSD; honoraria for consultations, lectures, training, and clinical trials and payment of conferences fees from Roche, Lilly, Novartis, Stemline, Pfizer, Medison, Exact Sciences, AstraZeneca, Gilead, and MSD; support for attending meetings from Roche, Gilead, and Pfizer; participation on board for AstraZeneca; and a fiduciary role as subject editor for the European Society for Medical Oncology (ESMO) Clinical Practice Guidelines Committee, outside the submitted work. PM reports support for attending meetings from AstraZeneca and Novartis, outside the submitted work. WC reports grant support from Cancer Council Victoria Grant in Aid; and honoraria for consultations, lectures, training, and clinical trials and payment of conferences fees from Eisai, outside the submitted work. SMW reports an advisory role for AstraZeneca; honoraria for consultations, lectures, training, and clinical trials and payment of conferences fees from Merck; and grant support from Cancer Research Society, outside the submitted work. CV reports advisory role for Eli Lilly, Novartis, AstraZeneca, Pfizer, Menarini Stemline, and Daiichi Sankyo; and speaker honoraria from Eli Lilly, Menarini Stemline, MSD, Novartis, Pfizer, Istituto Gentili, Accademia Nazionale di Medicina, Novartis, and Daiichi Sankyo outside the submitted work. MVD reports grant support from Roche (to their institution); consulting fees from Novartis, Eli Lilly, Seagen, Exact Science, Pfizer, Daiichi Sankyo, Gilead, MSD, AstraZeneca, and Roche; honoraria from Exact Sciences, Daiichi Sankyo, Novartis, Roche, Eli Lilly, and AstraZeneca; travel support from Eli Lilly, Roche, Gilead, and Daiichi Sankyo; participation on a Data Safety Monitoring Board or Advisory Board for Novartis, Eli Lilly, Pfizer, Daiichi Sankyo, Gilead, MSD, and AstraZeneca; and being listed as co-inventor in HER2DX patent applications, outside the summited work. AM reports consulting or advisory roles with Roche, Veracyte, and AstraZeneca; honoraria for consultations, lectures, training, or clinical trials and payment of conference fees from Seagen; and grant support from MSD, AstraZeneca, Novartis, and Veracyte, outside the submitted work. DCG reports advisory roles for Bayer, Merck KGaA, and Bristol Myers Squibb; speaker honoraria from Amgen, Merck KGaA, Bristol Myers Squibb, and Nobel; travel grants from MSD, Astellas, Bristol Myers Squibb, Amgen, Roche, Eczacıbaşı, and GSK, outside the submitted work. SEH reports advisory roles for AstraZeneca and Merck; honoraria for consultations, lectures, training, or clinical trials and payment of conferences fees from Lumicell; and grant support from the National Institutes of Health (NIH), Breast Cancer Research Foundation, and PCORI, outside the submitted work. LDM reports honoraria for consultations, lectures, training, or clinical trials and payment of conferences fees from AstraZeneca and MSD; and support for attending meetings from MSD, outside the submitted work. FP reports honoraria for advisory boards, activities as a speaker, and travel and research grants from Amgen, AstraZeneca, Daiichi Sankyo, Celgene, Eisai, Eli Lilly, Exact Sciences, Gilead, Ipsen, Italfarmaco, Menarini, MSD, Novartis, Pierre Fabre, Pfizer, Roche, Seagen, Takeda, and Viatris; and research funding from AstraZeneca, Eisai, and Roche, outside the submitted work. ZK reports honoraria for talks and educational materials from AstraZeneca and Pfizer, outside the submitted work. PAM reports speaker honoraria from AstraZeneca and Pfizer; consulting fees from Gilead, GSK, Novartis, and Pfizer; travel or meeting grants from Gilead, GSK, Immedica, and Pfizer; and participation on data safety monitoring or advisory board for GSK, outside the submitted work. GW reports honoraria for consultations, lectures, training, or clinical trials and payment of conferences fees from Merck, Daiichi Sankyo, Bristol-Myers Squibb, Roche, Pfizer, AstraZeneca, MSD, and Novartis; grant support from Novartis, Roche/Genentech, AstraZeneca/MedImmune, Lilly, GlaxoSmithKline, Novartis, Pfizer, Bristol-Myers Squibb Brazil, Roche, MSD, Merck, Bayer, Janssen, Astellas, Libbs, and Takeda; and support for attending meetings from AstraZeneca, outside the submitted work. HAAJ reports honoraria from AstraZeneca and Roche, outside submitted work. SR reports grant funding from Pfizer/Conquer Cancer, NIH, US Department of Defense, and the Centers for Disease Control and Prevention, outside the submitted work. LB reports speaker honoraria from Pfizer and patent PCT/EP2012/065661, outside the submitted work. MLa reports advisory role for Roche, Lilly, Novartis, AstraZeneca, Pfizer, Seagen, Gilead, MSD, Exact Sciences, Pierre Fabre, and Menarini; speaker honoraria from Roche, Lilly, Novartis, Pfizer, Sandoz, Libbs, Daiichi Sankyo, Takeda, Menarini, and AstraZeneca; travel grants from Gilead, Daiichi Sankyo, and Roche; and research funding (to their institution) from Gilead, outside the submitted work. All other authors declare no competing interests.
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