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JAMA Oncol. 2018 Aug 1;4(8):1059-1065. doi: 10.1001/jamaoncol.2018.0211.

Hormone Replacement Therapy After Oophorectomy and Breast Cancer Risk Among BRCA1 Mutation Carriers.

Author information

Women's College Research Institute, Women's College Hospital, Toronto, Ontario, Canada.
Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada.
International Hereditary Cancer Center, Department of Genetics and Pathology, Pomeranian Medical University, Szczecin, Poland.
Gynecology Oncology, Cedars Sinai Medical Center, Los Angeles, California.
Beth Israel Deaconess Medical Center, Boston, Massachusetts.
Inherited Cancer Research Group, The Norwegian Radium Hospital, Department for Medical Genetics, Department of Tumor Biology, Institute of Cancer Research, The Norwegian Radium Hospital; Oslo University Hospital, Oslo, Norway.
Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Toronto, Ontario, Canada.
Department of Preventive Medicine and Public Health, Creighton University School of Medicine, Omaha, Nebraska.
Division of Human Genetics, the Ohio State University Medical Center, Comprehensive Cancer Center, Columbus.
Toronto-Sunnybrook Regional Cancer Center, Toronto, Ontario, Canada.
Department of Obstetrics and Gynecology and Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria.
Program in Cancer Genetics, Department of Oncology and Human Genetics, McGill University, Montréal, Quebec, Canada.



Prophylactic bilateral salpingo-oophorectomy is recommended for BRCA1 mutation carriers to prevent ovarian cancer. Whether or not hormone replacement therapy (HRT) initiated after oophorectomy is associated with an increased risk of breast cancer has not been evaluated in a prospective study.


To determine the association between HRT use and BRCA1-associated breast cancer.

Design, Setting, and Participants:

A prospective, longitudinal cohort study of BRCA1 and BRCA2 mutation carriers from 80 participating centers in 17 countries was conducted between 1995 and 2017 with a mean follow-up of 7.6 years. Participants had sought genetic testing for a BRCA1 or BRCA2 mutation because of a personal or family history of breast and/or ovarian cancer. Carriers of BRCA1 mutation with no personal medical history of cancer who underwent bilateral oophorectomy following enrollment were eligible for the cohort study.


A follow-up questionnaire was administered every 2 years to obtain detailed information on HRT use. A left-truncated Cox proportional hazard analysis was used to estimate the hazard ratios (HRs) and 95% CIs associated with the initiation of HRT use postoophorectomy.

Main Outcomes and Measures:

Incident breast cancer.


A total of 872 BRCA1 mutation carriers with a mean postoophorectomy follow-up period of 7.6 years (range, 0.4-22.1) were included in this study. Mean (SD) age of participants was 43.4 (8.5) years. Among these, 92 (10.6%) incident breast cancers were diagnosed. Overall, HRT use after oophorectomy was not associated with an increased risk of breast cancer. The HR was 0.97 (95% CI, 0.62-1.52; P = .89) for ever use of any type of HRT vs no use; however, the effects of estrogen alone and combination hormonal therapy were different. After 10 years of follow-up, the cumulative incidence of breast cancer among women who used estrogen-alone HRT was 12% compared with 22% among women who used estrogen plus progesterone HRT (absolute difference, 10%; log rank P = .04).

Conclusions and Relevance:

These findings suggest that use of estrogen after oophorectomy does not increase the risk of breast cancer among women with a BRCA1 mutation and should reassure BRCA1 mutation carriers considering preventive surgery that HRT is safe. The possible adverse effect of progesterone-containing HRT warrants further study.

[Available on 2019-04-19]

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