Hormone Therapy After Oophorectomy and Breast Cancer Risk in Women With BRCA Pathogenic Variant

Risk-reducing bilateral salpingo-oophorectomy is recommended to substantially lower ovarian cancer risk in women carrying BRCA1 or BRCA2 pathogenic variant (PV). The use of hormone replacement therapy (HRT) after risk-reducing bilateral oophorectomy (RRBO), although generally recommended, remains debated due to concerns about its possible role in breast cancer (BC) risk.

To assess the possible association between HRT use and BC incidence after RRBO in women harboring a limited range of germline BRCA PVs.

This retrospective multicenter cohort study was conducted at 3 medical centers, including both referral and primary care facilities, in Israel. Cancer-free women (aged ≥18 years) with BRCA1 PV or BRCA2 PV, with no prior mastectomy, who underwent RRBO between January 1, 2000, and December 31, 2024, and who had at least 1 year of follow-up after RRBO were included.

HRT use after RRBO.

First diagnosis or incidence of invasive BC. BC diagnoses were ascertained through pathology reports and diagnostic codes used in the electronic health records; some were confirmed via participant interviews. HRT use was assessed through medical records, pharmacy dispensing data, clinic visits, and telephone interviews. Cox proportional hazards regression models, with HRT modeled as a time-varying covariate, evaluated the associations with BC risk while adjusting for potential confounders.

A total of 919 women (mean [SD] age at RRBO, 47.6 [8.9] years) were included, of whom 496 had BRCA1 PV and 423 had BRCA2 PV. During a mean (SD) follow-up of 8.8 (6.2) years, 144 women (16%) were diagnosed with invasive BC. Overall, 381 participants (42%) had ever used and 538 (58%) had never used HRT following RRBO. Ever use of HRT was not associated with increased BC risk (combined estrogen-progestin: hazard ratio [HR], 1.06 [95% CI, 0.67-1.68]; estrogen only: HR, 0.89 [95% CI, 0.48-1.63]). In duration of use analyses, each year of estrogen-only HRT was associated with a reduction in BC risk overall (HR, 0.90; 95% CI, 0.81-0.99) and a reduction among participants with BRCA1 PV (HR, 0.87; 95% CI, 0.77-0.98).

In this cohort study of women with BRCA PV who received HRT after RRBO, estrogen-only HRT was not associated with an increased risk of BC and was associated with a lower risk of BC among women with BRCA1 PV. Combined estrogen-progestin HRT was not associated with BC risk modification.