Study Suggests No Increased Breast Cancer Risk with Hormone Replacement Therapy after Risk-reducing Salpingo-oophorectomy

Hormone replacement therapy (HRT) does not increase the risk of breast cancer in women with BRCA1 or BRCA2 mutations who have undergone risk-reducing salpingo-oophorectomy (RRSO), suggest results of a prospective, observational study presented at the Cancer Prevention and Epidemiology Oral Abstract Session.

In this analysis of 1,299 BRCA1- or BRCA2-mutation carriers from the Prevention and Observation of Surgical Endpoints (PROSE) study group (Abstract 1501), there was no significant difference in the incidence of breast cancer in women who underwent RRSO and received HRT compared with those who underwent RRSO and did not receive HRT, after a mean follow up of 3 to 5 years.

The analysis included women enrolled at centers in the United States and Europe who had a deleterious BRCA1 or BRCA2 mutation with at least one ovary, no breast or ovarian cancer, no bilateral mastectomy prior to oophorectomy, and at least 6 months of follow up. The mean age of eligible participants was 37.7; 61% had a BRCA1 mutation and 39% had a BRCA2 mutation. One-quarter of participants (321 women) had undergone RRSO, and 45% of those individuals (144 women) subsequently used HRT.

Participants were stratified for age and treatment center and followed until the date of breast cancer diagnosis or censored upon mastectomy, ovarian cancer, death, or date of last contact.

In the entire evaluable population, 22% developed breast cancer and 13% developed breast cancer after RRSO, confirming the benefit of RRSO for breast cancer prevention. Among the 321 women who had undergone RRSO, the incidence of breast cancer was 14% in those receiving HRT (20 of 144 women) and 12% in those who never received HRT (22 of 177 women), a nonsignificant difference.

These data reflect a 44% reduction in the risk of breast cancer among women who underwent RRSO with no HRT compared with those who did not receive RRSO nor HRT (hazard ratio [HR]: 0.56; 95% CI [0.34, 0.93]).

Among women who underwent RRSO and who received subsequent HRT, the risk of breast cancer was reduced by 57% compared with no RRSO (HR: 0.43; 95% CI [0.26, 0.72]). This trend held true in both BRCA1 and BRCA2 carriers.

This may give some comfort to women considering mutational testing because of family background, suggested Susan M. Domchek, MD, of Abramson Cancer Center of the University of Pennsylvania. She explained that the prospect of undergoing surgically induced menopause without the benefit of HRT to relieve symptoms may deter some patients’ relatives from seeking testing.

“These data suggest that short-term HRT can be considered for BRCA1/2-mutation carriers undergoing early RRSO for ovarian and breast cancer risk reduction,” Dr. Domchek concluded.

A preliminary analysis by HRT type — available in 113 women — suggested that the type of HRT did not affect breast cancer risk, as neither combination HRT nor estrogenonly HRT increased the risk of breast cancer. However, the small patient numbers precluded definitive conclusions.

Discussant Lynn C. Hartmann, MD, of Mayo Clinic, urged caution in interpreting the results of observational trials such as this, as significant bias can be introduced. For example, physicians may be less likely to prescribe HRT to women whom they consider at risk of early breast cancer, which may alter the outcomes.

Dr. Hartmann suggested that a randomized trial would be needed to provide more conclusive answers.