Menopausal hormone therapy and the risk of breast cancer in women with a pathogenic variant in BRCA1 or BRCA2

BACKGROUND: Women with a pathogenic variant in BRCA1 or BRCA2 are at high risk of developing ovarian cancer and often recommended to undergo bilateral salpingo-oophorectomy at an early age resulting in surgical menopause. Menopausal hormone therapy (MHT) is an effective way to mitigate the adverse outcomes of early menopause; however, the safety of MHT on breast cancer risk in this population has not been established. METHODS: We conducted a prospective matched analysis of MHT use following menopause and breast cancer risk in BRCA carriers. Women who initiated MHT were matched one-to-one with women who had not initiated MHT by gene, year of birth, and age at menopause, resulting in 676 matched pairs. MHT use collected by questionnaire included formulation and mode of administration. RESULTS: After a mean of 5.6 years there were 87 incident breast cancer cases in the 676 exposed women (12·9%) and 128 cases in the 676 unexposed women (18·9%) (P = 0·002). Compared to their unexposed matched controls, women who used estrogen alone (E) experienced a significantly decreased risk of breast cancer (HR = 0·37; 95%: CI 0·24-0·57). There was no protective or adverse effect associated with the use of E plus progestogen (E + P) (HR = 0·94; 95%CI 0·54-1·63). CONCLUSIONS: Our findings suggest there is no significant increase in the risk of breast cancer in BRCA carriers with the use of MHT and that E alone might be protective.