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Hormone Replacement Therapy and Breast Cancer Risk After Oophorectomy in BRCA1-Mutation Carriers

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Key Points

  • No difference in risk of breast cancer was observed between hormone replacement therapy users and nonusers.
  • Use of estrogen plus progesterone was associated with higher risk vs use of estrogen-alone hormone replacement therapy. 

In a study reported in JAMA Oncology, Kotsopoulos et al found that use of hormone replacement therapy overall did not increase risk of breast cancer among BRCA1-mutation carriers after prophylactic bilateral salpingo-oophorectomy; however, use of estrogen-progesterone hormone replacement therapy appeared to be associated with increased risk vs estrogen alone.

Study Details

A prospective, longitudinal cohort study of BRCA1- and BRCA2-mutation carriers from 80 centers in 17 countries was conducted between 1995 and 2017 with a mean follow-up of 7.6 years. Participants had undergone genetic testing for BRCA1 or BRCA2 mutation on the basis of personal or family history of breast or ovarian cancer.

The current study included a total of 872 BRCA1-mutation carriers with no personal history of cancer with a mean postoophorectomy follow-up of 7.6 years. Patients had a mean age of 43.4 years. Questionnaires were administered every 2 years for information on hormone replacement therapy use.

Breast Cancer Risk

Among the 872 patients, 377 used hormone replacement therapy after oophorectomy, with a mean duration of hormone replacement therapy use of 3.9 years (range = 0.5–19 years); 259 (69%) used estrogen alone, 66 (18%) used estrogen plus progesterone, 40 (11%) used progesterone alone, and 80 (21%) used another formulation.

Overall, 92 patients (10.6%) had a diagnosis of incident breast cancer, with no significant difference in rates between hormone replacement therapy users vs nonusers (10.3% vs 10.7%, hazard ratio [HR] = 0.97, P = .89, on multivariate analysis). However, the 10-year cumulative incidence of breast cancer was higher among women who used estrogen plus progesterone vs those using estrogen-alone hormone replacement therapy (22% vs 12%, P = .04). This effect was stronger among women who underwent oophorectomy before age 45 years (24% vs 9%, P = .009). On multivariate analysis, hazard ratios were 0.73 (95% confidence interval [CI] = 0.41–1.32) for estrogen alone, 1.31 (95% CI = 0.66–2.57) for estrogen plus progesterone, and 1.29 (95% CI= 0.63–2.67) for other formulations.

The investigators concluded, “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 [hormone replacement therapy] is safe. The possible adverse effect of progesterone-containing [hormone replacement therapy] warrants further study.”

The study was supported by the Canadian Cancer Society Research Institute, Nebraska Department of Health and Human Services, and Liz’s Legacy fund.

Steven A. Narod, MD, of Women’s College Research Institute, Women’s College Hospital, Toronto, is the corresponding author for the JAMA Oncology article. 

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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