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Hormone Therapy After Oophorectomy and Breast Cancer Risk in Women With BRCA Pathogenic Variant
Shira Regev-Sadeh1,2,3, Rachel Michaelson-Cohen4,5,6, Dana Madorksy-Feldman7
1Department of Obstetrics and Gynecology, Carmel Medical Center, Haifa, Israel.
JAMA Network Open
|April 8, 2026
Summary
Hormone replacement therapy (HRT) use after risk-reducing bilateral salpingo-oophorectomy (RRBO) in women with BRCA pathogenic variants (PV) showed no increased breast cancer (BC) risk. Estrogen-only HRT was associated with a reduced BC risk in BRCA1 PV carriers.
Area of Science:
- Oncology
- Genetics
- Endocrinology
Background:
- Risk-reducing bilateral salpingo-oophorectomy (RRBO) is recommended for women with BRCA1 or BRCA2 pathogenic variants (PV) to lower ovarian cancer risk.
- Hormone replacement therapy (HRT) use post-RRBO is debated due to potential breast cancer (BC) risk concerns.
Purpose of the Study:
- To investigate the association between HRT use and BC incidence in women with BRCA PV after RRBO.
Main Methods:
- Retrospective cohort study at 3 Israeli medical centers.
- Included cancer-free women (≥18 years) with BRCA1/BRCA2 PV who underwent RRBO.
- Assessed HRT use and BC incidence using medical records, pharmacy data, and interviews.
- Analyzed data using Cox proportional hazards regression models.
Main Results:
- 919 women with BRCA PV underwent RRBO; 144 (16%) developed invasive BC during 8.8 years of follow-up.
- Ever HRT use was not associated with increased BC risk (combined estrogen-progestin: HR 1.06; estrogen-only: HR 0.89).
- Each year of estrogen-only HRT was linked to reduced BC risk (HR 0.90 overall, HR 0.87 in BRCA1 PV carriers).
Conclusions:
- Estrogen-only HRT post-RRBO in women with BRCA PV is not linked to increased BC risk.
- Estrogen-only HRT showed a reduced BC risk specifically in BRCA1 PV carriers.
- Combined estrogen-progestin HRT did not modify BC risk in this cohort.
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