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Hormone Therapy: Safe for BRCA1 Mutation Carriers?

Reassuring findings from a case-control study: Surprisingly, protection against breast cancer is a possible outcome.

Although women with BRCA1 mutations have a lifetime risk for breast cancer of 60% to 80%, this risk can be lowered substantially by prophylactic oophorectomy before menopause. Unfortunately, surgical castration can be associated with severe, sometimes disabling, vasomotor symptoms. However, concerns that hormone therapy might increase risk for breast cancer have led to uncertainty about whether BRCA mutation carriers who suffer from vasomotor symptoms after menopause or oophorectomy should use HT.

In a case-control study conducted in a population of postmenopausal BRCA1 mutation carriers at 55 centers in nine countries, investigators enrolled women who had reached menopause without diagnoses of breast cancer or other malignancies. Women who had undergone prophylactic mastectomies or who had received tamoxifen chemoprophylaxis were excluded. Cases (breast cancer diagnosed after menopause) and controls (no such diagnoses) were matched by birth year, age at menopause, and type of menopause (surgical or spontaneous). Risk for breast cancer was evaluated in 236 matched case-control pairs.

A higher proportion of controls than cases had used HT (29% vs. 20%; P=0.02; adjusted odds ratio, 0.58). ORs did not vary substantially between women who had experienced surgical or spontaneous menopause, by duration of HT use, or according to use of estrogen-only versus estrogen–progesterone HT.

Comment: Most U.S. women with known BRCA mutations now undergo prophylactic bilateral oophorectomy at the completion of childbearing. Following surgery, such women often face a dilemma: live with bothersome vasomotor symptoms or take HT with consequent anxiety about possible excess risk for breast cancer. This important study found no evidence of higher breast cancer risk with HT use in BRCA1 mutation carriers — and provided a surprising suggestion that HT can be protective. Although more research, particularly in BRCA2 mutation carriers, would be welcome, these results allow us to reassure women with BRCA1 mutations that use of menopausal HT is not contraindicated.

— Andrew M. Kaunitz, MD

Published in Journal Watch Women's Health October 23, 2008

Citation(s):

Eisen A et al. Hormone therapy and the risk of breast cancer in BRCA1 mutation carriers. J Natl Cancer Inst 2008 Oct 1; 100:1361.

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