BACKGROUND: The effect of risk-reducing salpingo-oophorectomy (RRSO) on breast cancer risk for BRCA1 and BRCA2 mutation carriers is uncertain. Retrospective analyses have suggested a protective effect but may be substantially biased. Prospective studies have had limited power, particularly for BRCA2 mutation carriers. Further, previous studies have not considered the effect of RRSO in the context of natural menopause. METHODS: A multi-centre prospective cohort of 2272 BRCA1 and 1605 BRCA2 mutation carriers was followed for a mean of 5.4 and 4.9 years, respectively; 426 women developed incident breast cancer. RRSO was modelled as a time-dependent covariate in Cox regression, and its effect assessed in premenopausal and postmenopausal women. RESULTS: There was no association between RRSO and breast cancer for BRCA1 (HR = 1.23; 95% CI 0.94-1.61) or BRCA2 (HR = 0.88; 95% CI 0.62-1.24) mutation carriers. For BRCA2 mutation carriers, HRs were 0.68 (95% CI 0.40-1.15) and 1.07 (95% CI 0.69-1.64) for RRSO carried out before or after age 45 years, respectively. The HR for BRCA2 mutation carriers decreased with increasing time since RRSO (HR = 0.51; 95% CI 0.26-0.99 for 5 years or longer after RRSO). Estimates for premenopausal women were similar. CONCLUSION: We found no evidence that RRSO reduces breast cancer risk for BRCA1 mutation carriers. A potentially beneficial effect for BRCA2 mutation carriers was observed, particularly after 5 years following RRSO. These results may inform counselling and management of carriers with respect to RRSO.

Academic Department of Medical Genetics National Institute for Health Research Cambridge Biomedical Research Centre University of Cambridge Cambridge UK

Cancer Epidemiology Division Cancer Council Victoria Melbourne Victoria Australia

Center for Familial Breast and Ovarian Cancer Center for Integrated Oncology Medical Faculty University Hospital Cologne Cologne Germany

Center for Molecular Medicine Cologne University of Cologne Cologne Germany

Centre Catherine de Sienne Service d'Oncologie Médicale Nantes France

Centre for Cancer Genetic Epidemiology Department of Oncology Strangeways Research Laboratory Worts Causeway University of Cambridge Cambridge CBI 8RN UK

Centre for Cancer Genetic Epidemiology Department of Public Health and Primary Care Strangeways Research Laboratory Worts Causeway University of Cambridge Cambridge CBI 8RN UK

Centre for Epidemiology and Biostatistics Melbourne School of Population and Global Health The University of Melbourne Melbourne VIC 3010 Australia

Centre Hospitalier Service Régional d'Oncologie Génétique Poitou Charentes Niort France

Clinical Genetics Guy's and St Thomas' NHS Foundation Trust London UK

DASC Oncogénétique Clinique Institut Paoli Calmettes Marseille France

Département de Médecine Oncologique Gustave Roussy Hôpital Universitaire Villejuif France

Department of Cancer Epidemiology and Genetics Masaryk Memorial Cancer Institute Zluty kopec 7 65653 Brno Czech Republic

Department of Clinical Genetics Amsterdam UMC Vrije Universiteit Amsterdam Amsterdam Netherlands

Department of Clinical Genetics Fox Chase Cancer Center Philadelphia PA USA

Department of Clinical Genetics Rigshospitalet Copenhagen University Hospital Copenhagen Denmark

Department of Clinical Genetics Royal Devon and Exeter Hospital Exeter UK

Department of Dermatology University of Utah School of Medicine 30 North 1900 East SOM 4B454 Salt Lake City UT 841232 USA

Department of Epidemiology Columbia University New York NY USA

Department of Epidemiology Netherlands Cancer Institute P O Box 90203 1006 BE Amsterdam The Netherlands

Department of Genetics and Pathology Pomeranian Medical University Unii Lubelskiej 1 Szczecin Poland

Department of Genetics University Medical Center Utrecht Utrecht The Netherlands

Department of Gynaecological Oncology University Medical Center Groningen University of Groningen Groningen The Netherlands

Department of Gynecology and Obstetrics Medical Faculty and University Hospital Carl Gustav Carus Technische Universität Dresden Dresden Germany

Department of Medical Oncology Family Center Clinic Erasmus MC Cancer Institute Rotterdam The Netherlands

Department of Medical Oncology Peter MacCallum Cancer Centre Locked Bag 1 A'Beckett St East Melbourne Victoria 8006 Australia

Department of Medicine and Stanford Cancer Institute Stanford University School of Medicine Stanford CA USA

Department of Medicine Huntsman Cancer Institute University of Utah Health Sciences Center Salt Lake City UT USA

Department of Molecular Genetics National Institute of Oncology Budapest Hungary

Department of Molecular Genetics University of Toronto Toronto Ontario Canada

Department of OB GYN and Comprehensive Cancer Center Medical University of Vienna Waehringer Guertel 18 20 A 1090 Vienna Austria

Department of Oncology Lund University Hospital Lund Sweden

Department of Surgical Oncology Erasmus MC Cancer Institute Rotterdam The Netherlands

Departments of Pediatrics and Medicine Columbia University Medical Center New York NY USA

Genomic Medicine Manchester Academic Health Sciences Centre Division of Evolution and Genomic Sciences Manchester University Central Manchester University Hospitals NHS Foundation Trust Manchester UK

Genomics Center Centre Hospitalier Universitaire de Québec Université Laval Research Center 2705 Laurier Boulevard Quebec City Quebec Canada

German Cancer Consortium Heidelberg Germany

Herbert Irving Comprehensive Cancer Center Columbia University Medical Center New York NY USA

Human Genetics Group and Genotyping Unit CEGEN Human Cancer Genetics Programme Spanish National Cancer Research Centre Madrid Spain

Independent Laboratory of Molecular Biology and Genetic Diagnostics Pomeranian Medical University Unii Lubelskiej 1 Szczecin Poland

INSERM U900 Paris France

Institut Curie Paris France

Institut Curie Service de Génétique Paris France

Institute for Medical Informatics Statistics and Epidemiology University of Leipzig Leipzig Germany

Institute of Genetic Medicine Centre for Life Newcastle Upon Tyne Hospitals NHS Trust Newcastle upon Tyne UK

Lunenfeld Tanenbaum Research Institute Sinai Health System Toronto Ontario Canada

Mines Paris Tech Fontainebleau France

Molecular Oncology Laboratory Hospital Clinico San Carlos IdISSC CIBERONC Madrid Spain

National Center for Tumor Diseases Partner Site Dresden Dresden Germany

Oncogenetics Team The Institute of Cancer Research and Royal Marsden NHS Foundation Trust London UK

Precision Medicine School of Clinical Sciences at Monash Health Monash University Clayton Victoria Australia

PSL Research University Paris France

Sheffield Clinical Genetics Service Sheffield Children's Hospital Sheffield UK

The Department of Oncology and Pathology Karolinska Institute 171 76 Stockholm Sweden

The Sir Peter MacCallum Department of Oncology University of Melbourne Parkville Australia

Unité d'Oncogénétique CHU Arnaud de Villeneuve Montpellier France

University of Southampton Faculty of Medicine Southampton University Hospitals NHS Trust Southampton UK

Yorkshire Regional Genetics Service Chapel Allerton Hospital and University of Leeds Leeds UK

Breast Cancer Res. 2020 Feb 26;22(1):25. doi: 10.1186/s13058-020-01259-w PubMed

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Correction to: Risk-reducing salpingo-oophorectomy, natural menopause, and breast cancer risk: an international prospective cohort of BRCA1 and BRCA2 mutation carriers