Estrogen-Only HRT After RRBO Linked to Lower Breast Cancer Risk in BRCA1 Carriers

Estrogen-only hormone replacement therapy after risk-reducing bilateral oophorectomy lowered the risk for breast cancer in women with a BRCA1 pathogenic variant. In a cohort of women with BRCA1 or BRCA2 pathogenic variants who underwent RRBO between 2000 and 2024 at three sites in Israel, fewer women who ever used HRT had incident invasive breast cancer compared with those who never used HRT.

Women with BRCA1 or BRCA2 PVs who underwent RRBO between 2000 and 2024 were evaluated for incident invasive breast cancer on the basis of HRT use. The women who ever used HRT (n=381) and never used HRT (n=538) were mean ages 43.5 and 50.4 years at RRBO, and 58% and 51% had a BRCA1 PV.

In the HRT cohort, HRT was initiated a median 0.78 months after RRBO, 68% used combined estrogen-progestin, and the median duration of use was 5.09 years. During an average follow-up of 8.8 years, fewer women who ever used HRT had incident breast cancer compared with those who never used HRT (11% vs 19%; P =.002).

Risk for breast cancer was lower among women with a BRCA2 PV relative to those with a BRCA1 PV (hazard ratio [HR], 0.46; P <.001). Compared with women who never used HRT, risk for breast cancer was lower with every additional year of estrogen-only HRT use (HR, 0.90; P =.04). This trend was driven by women who carried a BRCA1 PV (HR, 0.87; P =.02).

The findings were published in JAMA Network Open. The study may have included immortal time bias, as HRT was not initiated immediately after RRBO. The investigators said that in this cohort study of women harboring BRCA PV after RRBO, estrogen-only HRT after the surgical procedure was not associated with an increased risk of breast cancer and was associated with a reduced risk in women with BRCA1 PV.