Use of Systemic Hormone Therapy in BRCA Mutation Carriers

Susan Domchek, MD; Andrew M. Kaunitz, MD, FACOG, NCMP


Menopause. 2016;23(9):1026-1027. 

In This Article

Abstract and Introduction


As more women are being counseled and tested, clinicians increasingly encounter women with identified BRCA1 and BRCA2 gene mutations. Existing, albeit limited, data indicate that risks of breast cancer are not increased with use of systemic hormone therapy by menopausal BRCA mutation carriers with intact breasts. Young mutation carriers with or without intact breasts should not defer or avoid risk-reducing (and lifesaving) bilateral salpingo-oophorectomy because of concerns that subsequent use of systemic hormone therapy will elevate breast cancer risk.


As more BRCA mutation carriers are being identified, clinicians increasingly encounter patients with such mutations seeking advice regarding the use of systemic hormone therapy (HT). In BRCA1 carriers, the estimated cumulative risks of breast and ovarian cancer by age 70 range from 60% to 65% and 39% to 59%, respectively, and these risks range from 45% to 55% and 11% to 17%, respectively, in women who harbor BRCA2 mutations.[1,2] When performed in premenopausal women, bilateral salpingo-oophorectomy (BSO) reduces ovarian, fallopian tube, and peritoneal cancer risks by 72% to 80% and breast cancer risks by 46% to 48%.[3,4] Women mutation carriers with no personal history of breast or ovarian cancer (known as previvors in the BRCA community) should be encouraged to complete childbearing and undergo risk-reducing BSO by age 35 to 40 years. Women who carry a BRCA1 mutation have an estimated 4% risk of being diagnosed with ovarian cancer clinically or at the time of surgery before age 40. This risk increases to 14.2% if such women defer BSO until age 50.[4]

Without use of systemic HT, young surgically menopausal women in observational studies appear to have an elevated risk for cognitive impairment or dementia.[5] In addition, vasomotor symptoms are often more severe, and risks for osteoporosis and cardiovascular disease may be elevated in women with early menopause who are not treated with HT. Accordingly, in the absence of contraindications, use of systemic HT should be considered for women with early menopause and generally should be continued at least until the normal age of menopause.[6] However, mutation carriers may delay or avoid risk-reducing (and lifesaving) BSO because of concerns regarding the safety of systemic HT.[7]