Breast Cancer Research (Jan 2020)
Risk-reducing salpingo-oophorectomy, natural menopause, and breast cancer risk: an international prospective cohort of BRCA1 and BRCA2 mutation carriers
- Nasim Mavaddat,
- Antonis C. Antoniou,
- Thea M. Mooij,
- Maartje J. Hooning,
- Bernadette A. Heemskerk-Gerritsen,
- GENEPSO,
- Catherine Noguès,
- Marion Gauthier-Villars,
- Olivier Caron,
- Paul Gesta,
- Pascal Pujol,
- Alain Lortholary,
- EMBRACE,
- Daniel Barrowdale,
- Debra Frost,
- D. Gareth Evans,
- Louise Izatt,
- Julian Adlard,
- Ros Eeles,
- Carole Brewer,
- Marc Tischkowitz,
- Alex Henderson,
- Jackie Cook,
- Diana Eccles,
- HEBON,
- Klaartje van Engelen,
- Marian J. E. Mourits,
- Margreet G. E. M. Ausems,
- Linetta B. Koppert,
- John L. Hopper,
- Esther M. John,
- Wendy K. Chung,
- Irene L. Andrulis,
- Mary B. Daly,
- Saundra S. Buys,
- kConFab Investigators,
- Javier Benitez,
- Trinidad Caldes,
- Anna Jakubowska,
- Jacques Simard,
- Christian F. Singer,
- Yen Tan,
- Edith Olah,
- Marie Navratilova,
- Lenka Foretova,
- Anne-Marie Gerdes,
- Marie-José Roos-Blom,
- Flora E. Van Leeuwen,
- Brita Arver,
- Håkan Olsson,
- Rita K. Schmutzler,
- Christoph Engel,
- Karin Kast,
- Kelly-Anne Phillips,
- Mary Beth Terry,
- Roger L. Milne,
- David E. Goldgar,
- Matti A. Rookus,
- Nadine Andrieu,
- Douglas F. Easton,
- on behalf of IBCCS,
- kConFab,
- BCFR
Affiliations
- Nasim Mavaddat
- Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, Strangeways Research Laboratory, Worts Causeway, University of Cambridge
- Antonis C. Antoniou
- Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, Strangeways Research Laboratory, Worts Causeway, University of Cambridge
- Thea M. Mooij
- Department of Epidemiology, Netherlands Cancer Institute
- Maartje J. Hooning
- Department of Medical Oncology, Family Center Clinic, Erasmus MC Cancer Institute
- Bernadette A. Heemskerk-Gerritsen
- Department of Medical Oncology, Family Center Clinic, Erasmus MC Cancer Institute
- GENEPSO
- DASC, Oncogénétique Clinique, Institut Paoli-Calmettes
- Catherine Noguès
- DASC, Oncogénétique Clinique, Institut Paoli-Calmettes
- Marion Gauthier-Villars
- Institut Curie, Service de Génétique
- Olivier Caron
- Département de Médecine Oncologique, Gustave Roussy Hôpital Universitaire
- Paul Gesta
- Centre Hospitalier, Service Régional d’Oncologie Génétique Poitou-Charentes
- Pascal Pujol
- Unité d’Oncogénétique, CHU Arnaud de Villeneuve
- Alain Lortholary
- Centre Catherine de Sienne, Service d’Oncologie Médicale
- EMBRACE
- Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, Strangeways Research Laboratory, Worts Causeway, University of Cambridge
- Daniel Barrowdale
- Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, Strangeways Research Laboratory, Worts Causeway, University of Cambridge
- Debra Frost
- Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, Strangeways Research Laboratory, Worts Causeway, University of Cambridge
- D. Gareth Evans
- Genomic Medicine, Manchester Academic Health Sciences Centre, Division of Evolution and Genomic Sciences, Manchester University, Central Manchester, University Hospitals NHS Foundation Trust
- Louise Izatt
- Clinical Genetics, Guy’s and St Thomas’ NHS Foundation Trust
- Julian Adlard
- Yorkshire Regional Genetics Service, Chapel Allerton Hospital and University of Leeds
- Ros Eeles
- Oncogenetics Team, The Institute of Cancer Research and Royal Marsden NHS Foundation Trust
- Carole Brewer
- Department of Clinical Genetics, Royal Devon & Exeter Hospital
- Marc Tischkowitz
- Academic Department of Medical Genetics, National Institute for Health Research Cambridge Biomedical Research Centre, University of Cambridge
- Alex Henderson
- Institute of Genetic Medicine, Centre for Life, Newcastle Upon Tyne Hospitals NHS Trust
- Jackie Cook
- Sheffield Clinical Genetics Service, Sheffield Children’s Hospital
- Diana Eccles
- University of Southampton Faculty of Medicine, Southampton University Hospitals NHS Trust
- HEBON
- The Hereditary Breast and Ovarian Cancer Research Group Netherlands (HEBON), Coordinating Center: Netherlands Cancer Institute
- Klaartje van Engelen
- Department of Clinical Genetics, Amsterdam UMC, Vrije Universiteit Amsterdam
- Marian J. E. Mourits
- Department of Gynaecological Oncology, University Medical Center Groningen, University of Groningen
- Margreet G. E. M. Ausems
- Department of Genetics, University Medical Center Utrecht
- Linetta B. Koppert
- Department of Surgical Oncology, Erasmus MC Cancer Institute
- John L. Hopper
- Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne
- Esther M. John
- Department of Medicine and Stanford Cancer Institute, Stanford University School of Medicine
- Wendy K. Chung
- Departments of Pediatrics and Medicine, Columbia University Medical Center
- Irene L. Andrulis
- Department of Molecular Genetics, University of Toronto
- Mary B. Daly
- Department of Clinical Genetics, Fox Chase Cancer Center
- Saundra S. Buys
- Department of Medicine, Huntsman Cancer Institute, University of Utah Health Sciences Center
- kConFab Investigators
- Research Department, Peter MacCallum Cancer Centre
- Javier Benitez
- Human Genetics Group and Genotyping Unit, CEGEN, Human Cancer Genetics Programme, Spanish National Cancer Research Centre (CNIO)
- Trinidad Caldes
- Molecular Oncology Laboratory, Hospital Clinico San Carlos, IdISSC, CIBERONC (ISCIII)
- Anna Jakubowska
- Department of Genetics and Pathology, Pomeranian Medical University
- Jacques Simard
- Genomics Center, Centre Hospitalier Universitaire de Québec, Université Laval Research Center
- Christian F. Singer
- Department of OB/GYN and Comprehensive Cancer Center, Medical University of Vienna
- Yen Tan
- Department of OB/GYN and Comprehensive Cancer Center, Medical University of Vienna
- Edith Olah
- Department of Molecular Genetics, National Institute of Oncology
- Marie Navratilova
- Department of Cancer Epidemiology and Genetics, Masaryk Memorial Cancer Institute
- Lenka Foretova
- Department of Cancer Epidemiology and Genetics, Masaryk Memorial Cancer Institute
- Anne-Marie Gerdes
- Department of Clinical Genetics, Rigshospitalet, Copenhagen University Hospital
- Marie-José Roos-Blom
- Department of Epidemiology, Netherlands Cancer Institute
- Flora E. Van Leeuwen
- Department of Epidemiology, Netherlands Cancer Institute
- Brita Arver
- The Department of Oncology and Pathology, Karolinska Institute
- Håkan Olsson
- Department of Oncology, Lund University Hospital
- Rita K. Schmutzler
- Center for Familial Breast and Ovarian Cancer, Center for Integrated Oncology (CIO), Medical Faculty, University Hospital Cologne
- Christoph Engel
- Institute for Medical Informatics, Statistics and Epidemiology, University of Leipzig
- Karin Kast
- Department of Gynecology and Obstetrics, Medical Faculty and University Hospital Carl Gustav Carus, Technische Universität Dresden
- Kelly-Anne Phillips
- Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne
- Mary Beth Terry
- Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center
- Roger L. Milne
- Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne
- David E. Goldgar
- Department of Dermatology, University of Utah School of Medicine
- Matti A. Rookus
- Department of Epidemiology, Netherlands Cancer Institute
- Nadine Andrieu
- INSERM, U900
- Douglas F. Easton
- Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, Strangeways Research Laboratory, Worts Causeway, University of Cambridge
- on behalf of IBCCS
- kConFab
- BCFR
- DOI
- https://doi.org/10.1186/s13058-020-1247-4
- Journal volume & issue
-
Vol. 22,
no. 1
pp. 1 – 11
Abstract
Abstract 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.
Keywords
