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Risk-reducing salpingo-oophorectomy, natural menopause, and breast cancer risk: an international prospective cohort of BRCA1 and BRCA2 mutation carriers
N. Mavaddat, AC. Antoniou, TM. Mooij, MJ. Hooning, BA. Heemskerk-Gerritsen, GENEPSO, C. Noguès, M. Gauthier-Villars, O. Caron, P. Gesta, P. Pujol, A. Lortholary, EMBRACE, D. Barrowdale, D. Frost, DG. Evans, L. Izatt, J. Adlard, R. Eeles, C....
Language English Country Great Britain
Document type Journal Article, Multicenter Study, Research Support, N.I.H., Intramural, Research Support, Non-U.S. Gov't
Grant support
C12292/A11174
Cancer Research UK - United Kingdom
R01 CA159868
NCI NIH HHS - United States
C1287/23382
Cancer Research UK - United Kingdom
GPH-129344
CIHR - Canada
C1287/A17523
Cancer Research UK - United Kingdom
C1287/A16563
Cancer Research UK - United Kingdom
C12292/A20861
Cancer Research UK - United Kingdom
UL1 TR001863
NCATS NIH HHS - United States
UM1 CA164920
NCI NIH HHS - United States
NLK
BioMedCentral
from 1999-12-01
BioMedCentral Open Access
from 1999
Directory of Open Access Journals
from 2000
Free Medical Journals
from 1999 to 2 years ago
PubMed Central
from 1999
Europe PubMed Central
from 1999
ProQuest Central
from 2015-01-01
Open Access Digital Library
from 1999-07-01
Open Access Digital Library
from 1999-01-01
Open Access Digital Library
from 2000-01-01
Health & Medicine (ProQuest)
from 2015-01-01
ROAD: Directory of Open Access Scholarly Resources
from 1999
Springer Nature OA/Free Journals
from 1999-12-01
- MeSH
- Risk Reduction Behavior MeSH
- Adult MeSH
- Incidence MeSH
- Cohort Studies MeSH
- Middle Aged MeSH
- Humans MeSH
- Menopause MeSH
- International Agencies MeSH
- Mutation * MeSH
- Breast Neoplasms epidemiology genetics pathology surgery MeSH
- Prospective Studies MeSH
- BRCA1 Protein genetics MeSH
- BRCA2 Protein genetics MeSH
- Salpingo-oophorectomy methods MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Multicenter Study MeSH
- Research Support, Non-U.S. Gov't MeSH
- Research Support, N.I.H., Intramural MeSH
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.
Centre Catherine de Sienne Service d'Oncologie Médicale Nantes France
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 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 Genetics University Medical Center Utrecht Utrecht The Netherlands
Department of Molecular Genetics National Institute of Oncology Budapest Hungary
Department of Oncology Lund University Hospital Lund Sweden
Department of Surgical Oncology Erasmus MC Cancer Institute Rotterdam The Netherlands
Institut Curie Service de Génétique Paris France
Institute for Medical Informatics Statistics and Epidemiology University of Leipzig Leipzig Germany
Molecular Oncology Laboratory Hospital Clinico San Carlos IdISSC CIBERONC Madrid Spain
Oncogenetics Team The Institute of Cancer Research and Royal Marsden NHS Foundation Trust London UK
Sheffield Clinical Genetics Service Sheffield Children's Hospital Sheffield UK
Unité d'Oncogénétique CHU Arnaud de Villeneuve Montpellier France
Yorkshire Regional Genetics Service Chapel Allerton Hospital and University of Leeds Leeds UK
References provided by Crossref.org
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