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J Natl Cancer Inst. 2016 Sep 6;109(1). pii: djw177. doi: 10.1093/jnci/djw177. Print 2017 Jan.

Bilateral Oophorectomy and Breast Cancer Risk in BRCA1 and BRCA2 Mutation Carriers.

Author information

1
Women's College Research Institute, Women's College Hospital, Toronto, ON, Canada.
2
International Hereditary Cancer Center, Department of Genetics and Pathology, Pomeranian Medical University, Szczecin, Poland.
3
Department of Obstetrics and Gynecology and Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria.
4
Department for Medical Genetics, Inherited Cancer Research Group, and Department of Tumor Biology, Institute of Cancer Research, Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway.
5
Department of Preventive Medicine and Public Health, Creighton University School of Medicine, Omaha, NE, USA.
6
Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Toronto, ON, Canada.
7
Gynecology Oncology, Cedars Sinai Medical Center, Los Angeles, CA, USA.
8
Program in Cancer Genetics, Department of Oncology and Human Genetics, McGill University, Montréal, QC, Canada.
9
Department of Population Sciences, Beckman Research Institute of City of Hope, Duarte, CA, USA.
10
Division of Human Genetics, The Ohio State University Medical Center, Comprehensive Cancer Center, Columbus, OH, USA.
11
Beth Israel Deaconess Medical Center, Boston, MA, USA.
12
City of Hope National Medical Center, Duarte, CA, USA.
13
Toronto-Sunnybrook Regional Cancer Center, Toronto, ON, Canada.
14
Faculty of Nursing, University of Toronto, ON, Canada.
15
Genomic Medicine Institute and Center for Personalized Genetic Healthcare, Cleveland Clinic, Cleveland, OH, USA.
16
Moffitt Cancer Center, Departments of Cancer Epidemiology, Biostatistics, Anatomic Pathology, and Experimental Therapeutics, Tampa, FL, USA.
17
Genomic Medicine, Manchester Academic Health Science Centre, University of Manchester, Manchester, UK.

Abstract

Background:

Whether oophorectomy reduces breast cancer risk among BRCA mutation carriers is a matter of debate. We undertook a prospective analysis of bilateral oophorectomy and breast cancer risk in BRCA mutation carriers.

Methods:

Subjects had no history of cancer, had both breasts intact, and had information on oophorectomy status (n = 3722). Women were followed until breast cancer diagnosis, prophylactic bilateral mastectomy, or death. A Cox regression model was used to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) of breast cancer associated with oophorectomy (coded as a time-dependent variable). All statistical tests were two-sided.

Results:

Over a mean follow-up of 5.6 years, 350 new breast cancers were diagnosed. Among women with a BRCA1 or BRCA2 mutation, oophorectomy was not associated with breast cancer risk compared with women who did not undergo an oophorectomy. The age-adjusted hazard ratio associated with oophorectomy was 0.96 (95% CI = 0.73 to 1.26, P = 76) for BRCA1 and was 0.65 (95% CI = 0.37 to 1.16, P = 14) for BRCA2 mutation carriers. In stratified analyses, the effect of oophorectomy was statistically significant for breast cancer in BRCA2 mutation carriers diagnosed prior to age 50 years (age-adjusted HR = 0.18, 95% CI = 0.05 to 0.63, P = 007). Oophorectomy was not associated with risk of breast cancer prior to age 50 years among BRCA1 mutation carriers (age-adjusted HR = 0.79, 95% CI = 0.55 to 1.13, P = 51).

Conclusions:

Findings from this large prospective study support a role of oophorectomy for the prevention of premenopausal breast cancer in BRCA2, but not BRCA1 mutation carriers. These findings warrant further evaluation.

Comment in

PMID:
27601060
DOI:
10.1093/jnci/djw177
[Indexed for MEDLINE]

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