Study Suggests Estrogen-Only HRT May Lower Breast Cancer Risk in Women with BRCA1: reveals Research

Navigating Hormone Therapy Choices After Oophorectomy

For women carrying BRCA1 or BRCA2 pathogenic variants, the decision to undergo risk-reducing bilateral salpingo-oophorectomy (RRBO) can be life-changing, significantly lowering the risk of ovarian cancer. However, the onset of early menopause brings its own challenges—hot flashes, bone loss, and cardiovascular risks—making hormone replacement therapy (HRT) an appealing but controversial option. A new large-scale study published in JAMA Network Open now sheds important light on the safety of HRT for this high-risk population.

What Did the Study Investigate?

Researchers conducted a retrospective multicenter cohort study involving 919 women with BRCA1 or BRCA2 variants in Israel. All participants had undergone RRBO between 2000 and 2024, were cancer-free at the time, and had at least one year of follow-up. The study’s primary focus: Does HRT after RRBO increase the risk of breast cancer in this vulnerable group?

Key Findings: Estrogen-Only HRT Stands Out

After an average follow-up of nearly nine years, the study found that 16% of the participants were diagnosed with invasive breast cancer. Importantly:

Estrogen-only HRT was NOT linked to an increased breast cancer risk.

In women with BRCA1 variants, each year of estrogen-only HRT was actually associated with a 13% reduction in breast cancer risk.

Combined estrogen-progestin HRT did not significantly affect breast cancer risk in either BRCA1 or BRCA2 carriers.

These findings are especially reassuring for women with BRCA1 who might need HRT after early menopause.

The Subtleties: Not All Hormones Are Equal

Why the difference? The study highlights that BRCA1-related breast cancers are often triple-negative and may be more susceptible to progestin-driven pathways that promote tumor growth. Estrogen-only therapy bypasses this risk and might even provide a protective effect. For BRCA2 carriers, neither estrogen-only nor combined therapy made a statistically significant difference in breast cancer risk.

Additionally, the research found that previous use of progestin-only contraceptives (like the levonorgestrel-releasing IUD) was associated with a higher breast cancer risk in women with BRCA1 variants.

Personalized Care Is Critical

The study’s authors urge individualized, multidisciplinary counseling for women with BRCA mutations considering HRT after RRBO. Estrogen-only therapy appears to be a safer option for those with BRCA1, but combined therapy should be approached cautiously, especially for long-term use in younger women.

Takeaways for Patients and Clinicians

Estrogen-only HRT after RRBO may lower breast cancer risk in BRCA1 carriers.

No significant increase in breast cancer risk was linked to HRT in BRCA2 carriers.

Combined HRT did not modify breast cancer risk but warrants close consideration.

Prior use of progestin-only IUDs may elevate breast cancer risk in BRCA1 carriers.

Decision-making should be highly personalized and multidisciplinary.

Citation:

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 Network Open. 2026;9(4):e265648. doi:10.1001/jamanetworkopen.2026.5648