Estrogen HRT Post-Oophorectomy Doesn’t Increase BRCA1 Carrier BC Risk

Women harboring BRCA1 germline mutations have an estimated 44% lifetime risk for developing ovarian cancer. Bilateral salpingo-oophorectomy is the most effective prophylactic measure to reduce the risk of ovarian cancer in these women. However, this surgical intervention is associated with early menopause and long-term consequences of abrupt ovarian hormonal withdrawal.  Hormone replacement therapy (HRT) is often prescribed to mitigate adverse effects of early menopause, but data from the Woman’s Health Initiative randomized controlled study raised the concern that HRT may be associated with an increased risk of breast cancer and cardiovascular disease. A recent, prospective, longitudinal, cohort study investigated the association between HRT and breast cancer risk in BRCA1 mutation carriers who underwent oophorectomy.

Of the 872 BRCA1 mutation carriers enrolled in this study, 377 (43%) used HRT post-oophorectomy and 495 (57%) did not. With a mean follow-up of 7.6 years post-oophorectomy, 10.6% of patients developed breast cancer, with an annual breast cancer risk of 1.4%. There was no difference in the incidence of breast cancer between patients who received HRT and those who did not (10.3% vs 10.7%; P = .86). However, patients who received HRT with estrogen alone had lower incidence of breast cancer than patients who received combined HRT of estrogen and progesterone (12% vs 22%; P = .04). This association was stronger in women who underwent oophorectomy prior to age 45. In these patients, each year of estrogen HRT was associated with a statistically significant 18% reduction in breast cancer risk, while each year of progesterone-containing HRT was associated with a nonsignificant 14% increase in breast cancer risk. There was no association between HRT use and breast cancer among women who underwent oophorectomy after age 45.

The investigators concluded that use of estrogen alone, following prophylactic oophorectomy, does not increase the risk of breast cancer in women with BRCA1 mutations and can be considered a safe treatment. The potential link between progesterone-containing regimens and breast cancer should be investigated further, particularly in women under the age of 45.

JAMA Oncol. 2018 April 19 [Epub ahead of print].

Clinical Opinion Poll

What frontline therapy would you recommend for a 49 y/o woman diagnosed with low tumor burden metastatic ALK+ NSCLC (lung and liver metastases, normal brain MRI, PS0)?