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Breast Cancer Res. 2020 Jan 16;22(1):8. doi: 10.1186/s13058-020-1247-4.

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

Author information

1
Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, Strangeways Research Laboratory, Worts Causeway, University of Cambridge, Cambridge, CBI 8RN, UK. nm274@medschl.cam.ac.uk.
2
Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, Strangeways Research Laboratory, Worts Causeway, University of Cambridge, Cambridge, CBI 8RN, UK.
3
Department of Epidemiology, Netherlands Cancer Institute, P.O. Box 90203, 1006 BE, Amsterdam, The Netherlands.
4
Department of Medical Oncology, Family Center Clinic, Erasmus MC Cancer Institute, Rotterdam, The Netherlands.
5
DASC, Oncogénétique Clinique, Institut Paoli-Calmettes, Marseille, France.
6
Institut Curie, Service de Génétique, Paris, France.
7
Département de Médecine Oncologique, Gustave Roussy Hôpital Universitaire, Villejuif, France.
8
Centre Hospitalier, Service Régional d'Oncologie Génétique Poitou-Charentes, Niort, France.
9
Unité d'Oncogénétique, CHU Arnaud de Villeneuve, Montpellier, France.
10
Centre Catherine de Sienne, Service d'Oncologie Médicale, Nantes, France.
11
Genomic Medicine, Manchester Academic Health Sciences Centre, Division of Evolution and Genomic Sciences, Manchester University, Central Manchester, University Hospitals NHS Foundation Trust, Manchester, UK.
12
Clinical Genetics, Guy's and St Thomas' NHS Foundation Trust, London, UK.
13
Yorkshire Regional Genetics Service, Chapel Allerton Hospital and University of Leeds, Leeds, UK.
14
Oncogenetics Team, The Institute of Cancer Research and Royal Marsden NHS Foundation Trust, London, UK.
15
Department of Clinical Genetics, Royal Devon & Exeter Hospital, Exeter, UK.
16
Academic Department of Medical Genetics, National Institute for Health Research Cambridge Biomedical Research Centre, University of Cambridge, Cambridge, UK.
17
Institute of Genetic Medicine, Centre for Life, Newcastle Upon Tyne Hospitals NHS Trust, Newcastle upon Tyne, UK.
18
Sheffield Clinical Genetics Service, Sheffield Children's Hospital, Sheffield, UK.
19
University of Southampton Faculty of Medicine, Southampton University Hospitals NHS Trust, Southampton, UK.
20
Department of Clinical Genetics, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, Netherlands.
21
Department of Gynaecological Oncology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
22
Department of Genetics, University Medical Center Utrecht, Utrecht, The Netherlands.
23
Department of Surgical Oncology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands.
24
Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, VIC, 3010, Australia.
25
Department of Medicine and Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA, USA.
26
Departments of Pediatrics and Medicine, Columbia University Medical Center, New York, NY, USA.
27
Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center, New York, NY, USA.
28
Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada.
29
Lunenfeld-Tanenbaum Research Institute, Sinai Health System, Toronto, Ontario, Canada.
30
Department of Clinical Genetics, Fox Chase Cancer Center, Philadelphia, PA, USA.
31
Department of Medicine, Huntsman Cancer Institute, University of Utah Health Sciences Center, Salt Lake City, UT, USA.
32
Human Genetics Group and Genotyping Unit, CEGEN, Human Cancer Genetics Programme, Spanish National Cancer Research Centre (CNIO), Madrid, Spain.
33
Molecular Oncology Laboratory, Hospital Clinico San Carlos, IdISSC, CIBERONC (ISCIII), Madrid, Spain.
34
Department of Genetics and Pathology, Pomeranian Medical University, Unii Lubelskiej 1, Szczecin, Poland.
35
Independent Laboratory of Molecular Biology and Genetic Diagnostics, Pomeranian Medical University, Unii Lubelskiej 1, Szczecin, Poland.
36
Genomics Center, Centre Hospitalier Universitaire de Québec, Université Laval Research Center, 2705 Laurier Boulevard, Quebec City, Quebec, Canada.
37
Department of OB/GYN and Comprehensive Cancer Center, Medical University of Vienna, Waehringer Guertel 18-20, A 1090, Vienna, Austria.
38
Department of Molecular Genetics, National Institute of Oncology, Budapest, Hungary.
39
Department of Cancer Epidemiology and Genetics, Masaryk Memorial Cancer Institute, Zluty kopec 7, 65653, Brno, Czech Republic.
40
Department of Clinical Genetics, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.
41
The Department of Oncology and Pathology, Karolinska Institute, 171 76, Stockholm, Sweden.
42
Department of Oncology, Lund University Hospital, Lund, Sweden.
43
Center for Familial Breast and Ovarian Cancer, Center for Integrated Oncology (CIO), Medical Faculty, University Hospital Cologne, Cologne, Germany.
44
Center for Molecular Medicine Cologne (CMMC), University of Cologne, Cologne, Germany.
45
Institute for Medical Informatics, Statistics and Epidemiology, University of Leipzig, Leipzig, Germany.
46
Department of Gynecology and Obstetrics, Medical Faculty and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.
47
National Center for Tumor Diseases (NCT), Partner Site Dresden, Dresden, Germany.
48
German Cancer Consortium (DKTK), Dresden and German Cancer Research Center (DKFZ), Heidelberg, Germany.
49
The Sir Peter MacCallum Department of Oncology, University of Melbourne, Parkville, Australia.
50
Department of Medical Oncology Peter MacCallum Cancer Centre, Locked Bag 1, A'Beckett St, East Melbourne, Victoria, 8006, Australia.
51
Department of Epidemiology, Columbia University, New York, NY, USA.
52
Cancer Epidemiology Division, Cancer Council Victoria, Melbourne, Victoria, Australia.
53
Precision Medicine, School of Clinical Sciences at Monash Health, Monash University, Clayton, Victoria, Australia.
54
Department of Dermatology, University of Utah School of Medicine, 30 North 1900 East, SOM 4B454, Salt Lake City, UT, 841232, USA.
55
INSERM, U900, Paris, France.
56
Institut Curie, Paris, France.
57
Mines Paris Tech, Fontainebleau, France.
58
PSL Research University, Paris, France.
59
Centre for Cancer Genetic Epidemiology, Department of Oncology, Strangeways Research Laboratory, Worts Causeway, University of Cambridge, Cambridge, CBI 8RN, UK.

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:

BRCA1; BRCA2; Breast cancer; Mutation; Risk-reducing salpingo-oophorectomy

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