Menopausal Hormone Therapy and Risk for Breast Cancer in BRCA1 Mutation Carriers

Andrew M. Kaunitz, MD


May 17, 2018

Hello. I am Andrew Kaunitz, professor and associate chair in the Department of Obstetrics and Gynecology at the University of Florida College of Medicine in Jacksonville.

Women with BRCA mutations have high lifetime risks for breast and ovarian cancer.[1] Prophylactic salpingo-oophorectomy reduces future risk for ovarian cancer in such women. However, they may be reluctant to use menopausal hormone therapy (HT) following oophorectomy due to concerns that HT might elevate breast cancer risk.

In a recent publication in JAMA Oncology,[2] investigators reported findings from an international cohort study which prospectively followed women with BRCA1 mutations, intact breasts, and no history of breast cancer following oophorectomy.

Among almost 900 BRCA1 carriers, more than 40% used HT after oophorectomy. The mean duration of HT use following risk-reducing gynecologic surgery was almost 4 years. More than two thirds of the women took estrogen therapy alone, and almost one fifth used estrogen plus progestogen (EPT). Women who used HT were younger at the time of oophorectomy (mean age, 43 years) compared with 48 years for mutation carriers who did not use HT postoperatively.

During follow-up, invasive breast cancer was diagnosed in 10%-11% of women in the overall cohort, whether or not HT was used. With respect to the type of HT used, the estimated 10-year risk for breast cancer was 12% with estrogen therapy alone, and 22% (significantly higher) with EPT. This difference was even more striking among women who underwent risk-reducing oophorectomy before age 45 years.[2]

Given their high lifetime risk for ovarian cancer, BRCA carriers who have completed childbearing are encouraged to proceed with risk-reducing gynecologic surgery. However, young women who undergo oophorectomy without HT face severe vasomotor symptoms along with elevated risks for osteoporosis, cardiovascular disease, and cognitive decline.

The substantial reduction in breast cancer risk associated with estrogen-only therapy suggests that in BRCA1 carriers with intact breasts who have completed childbearing, hysterectomy (which eliminates the need for progestogen therapy) should be incorporated into risk-reducing gynecologic surgery.

A last point is that the findings of this important study in high-risk women parallel the results of the large randomized Women's Health Initiative trial,[3] which was performed in the general population of menopausal women. That trial also found that while EPT modestly elevates risk for breast cancer, estrogen therapy reduces the risk.

Thank you for the honor of your time. I am Andrew Kaunitz.


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