Post-Oophorectomy Hormone Replacement Therapy Safe for BRCA1/2 Mutation Carriers

Women who present with BRCA1 and BRCA2 mutation face an increased risk of breast and ovarian cancer.

Susan M. Domchek, MD

Women who present with BRCA1 and BRCA2 mutation face an increased risk of breast and ovarian cancer. Although risk-reducing salpingo-oophorectomy (RRSO) can significantly reduce cancer risk, BRCA1/2 mutation carriers aged <40 years can be understandably reluctant to experience the significant menopausal symptoms and other health problems associated with ovary removal.

Hormone replacement therapy (HRT) can effectively mitigate many of the side effects of early menopause for RRSO candidates; however, there has been concern among the lay public that HRT can increase the risk of breast cancer. Research presented on Monday at the ASCO conference in Chicago conclusively demonstrated that HRT is not only safe following RRSO, it may decrease the risk of breast cancer.

“We know that oophorectomy is a good thing for BRCA 1 and 2 mutation carriers,” said Susan M. Domchek, MD, director of the Cancer Risk Evaluation Program at the University of Pennsylvania’s Abramson Cancer Center in Philadelphia and lead author of the study, in an interview with “But we’re having young women undergo oophorectomy, and their question is if they can safely take hormone replacement therapy after their oophorectomy in order to make the whole procedure more palatable.”

Domchek and her colleagues conducted a prospective study of 1299 BRCA1/2 (n = 795/504, respectively) mutation carriers from the Prevention and Observation of Surgical Endpoints (PROSE) consortium database. The cohort was divided into those who had taken HRT and those who had not.

The researchers reported that women who underwent RRSO had a lower risk of breast cancer than those who did not, with 14% of the women who took HRT after surgery developing breast cancer compared with 12% of the women who did not take HRT after surgery. The difference was not statistically significant, according to the researchers.

Domchek said that women who have BRCA1/2 mutations and who have had their ovaries removed while they are quite young should discuss HRT with their referring physician and oncologist, and it should be considered as an option for treating menopausal symptoms.

Study data have shown definitively that oophorectomy reduces ovarian and breast cancer incidence in these women and reduces their mortality due to those cancers. But Domchek noted that it is also important to pay attention to the role that hormone depletion following preventive oophorectomy plays in women’s future health.

“It is unfortunate to have women choose not to have an oophorectomy, or wait too long, because they are worried about menopausal symptoms and are told they can’t take HRT,” she said. “Our data say that is not the case—these drugs do not increase their risk of breast cancer.”

Domchek SM, Friebel T, Neuhausen SL, et al. Is hormone replacement therapy (HRT) following risk-reducing salpingo-oophorectomy (RRSO) in BRCA1 (B1)- and BRCA2 (B2)-mutation carriers associated with an increased risk of breast cancer? J Clin Oncol. 29:2011 (suppl; abstract 1501).