Research Summary

Study: HRT After Oophorectomy Did Not Raise Breast Cancer Risk in BRCA Carriers

Edited by:
Ashton L. Stahl

Key Highlights

  • In 919 women with BRCA1 or BRCA2 pathogenic variants, hormone replacement therapy after risk-reducing bilateral oophorectomy was not associated with an increased risk of invasive breast cancer.
  • Estrogen-only HRT was associated with a lower breast cancer risk per year of use overall and among women with BRCA1 pathogenic variants.
  • Combined estrogen-progestin HRT was not associated with breast cancer risk modification in the overall cohort.
  • Prior levonorgestrel-releasing intrauterine device use was associated with increased breast cancer risk, particularly in women with BRCA1 pathogenic variants.

According to a retrospective multicenter cohort study published in JAMA Network Open, women with BRCA1 and BRCA2 pathogenic variants who used hormone replacement therapy after a risk-reducing bilateral oophorectomy did not show a higher risk of invasive breast cancer. The analysis also found that estrogen-only therapy was associated with a lower breast cancer risk per year of use, particularly among women with BRCA1 pathogenic variants.

The study included cancer-free women aged 18 years or older with BRCA1 or BRCA2 pathogenic or likely pathogenic variants who underwent a risk-reducing bilateral oophorectomy between January 1, 2000, and December 31, 2024, at 3 medical centers in Israel. Women with prior cancer, a prior mastectomy, or who had less than 1 year of follow-up were excluded. HRT exposure after surgery was determined using medical records, pharmacy dispensing data, clinic documentation, and telephone interviews. Investigators used Cox proportional hazards models, with HRT treated as a time-varying covariate, to assess associations with invasive breast cancer risk after adjustment for prespecified confounders.

Study Findings

Among the 2,017 identified women, 919 met eligibility criteria, including 496 with BRCA1 pathogenic variants and 423 with BRCA2 pathogenic variants. The mean age at oophorectomy was 47.6 years, and the mean follow-up was 8.8 years. Only 381 women (42%) had ever used HRT after surgery, and 538 (58%) had never used it. During follow-up, 144 women (16%) developed invasive breast cancer. Among HRT users, the mean treatment duration was 5.09 years; 68% used combined estrogen-progestin therapy and 31% used estrogen-only therapy.

In multivariable analyses, ever use of HRT was not associated with increased breast cancer risk, either for combined estrogen-progestin therapy (hazard ratio [HR], 1.06; 95% CI, 0.67-1.68) or estrogen-only therapy (HR, 0.89; 95% CI, 0.48-1.63). In duration analyses, each year of estrogen-only HRT was associated with lower breast cancer risk overall (HR, 0.90; 95% CI, 0.81-0.99) and among women with BRCA1 pathogenic variants (HR, 0.87; 95% CI, 0.77-0.98). Combined estrogen-progestin HRT was not significantly associated with breast cancer risk overall. Prior levonorgestrel-releasing intrauterine device use was associated with increased risk overall (HR, 1.69; 95% CI, 1.09-2.61) and in the BRCA1 subgroup (HR, 2.00; 95% CI, 1.18-3.36).

Clinical Implications

According to the study authors, the findings suggest that estrogen-only HRT after a risk-reducing bilateral oophorectomy does not increase breast cancer risk and may be associated with a lower risk in women with BRCA1 pathogenic variants, while combined estrogen-progestin HRT was not consistently associated with risk modification. The authors stated that the results support multidisciplinary counseling and individualized decision-making regarding HRT and contraceptive choices in women with BRCA1 or BRCA2 pathogenic variants.

The authors noted several limitations, including the observational design, which may introduce residual confounding, and potential recall bias in self-reported exposure data. They also reported that missing data led to the exclusion of some participants, potentially introducing selection bias.

Expert Commentary

“Estrogen-only HRT after the surgical procedure was not associated with an increased risk of BC and was associated with a reduced risk in women with BRCA1 PV. Combined estrogen-progestin HRT was not consistently associated with BC risk modification,” the researchers concluded.

Reference: Regev-Sadeh S, Michaelson-Cohen R, Madorksy-Feldman D, et al. Hormone therapy after oophorectomy and breast cancer risk in women with BRCA pathogenic variant. JAMA Netw Open. 2026;9(4):e265648. doi:10.1001/jamanetworkopen.2026.5648