Letrozole to prevent breast cancer in postmenopausal women with BRCA1/2 mutations (LIBER study).

BACKGROUND: Women carrying a germline BRCA1 or BRCA2 mutation (gBRCAm) have a 70 % lifetime risk of breast cancer (BC). Aromatase inhibitors (AI) decrease BC incidence in high-risk populations but have not been specifically assessed in gBRCAm carriers. METHODS: LIBER was a randomized, double-blind, placebo-controlled, phase III trial. Post-menopausal women aged between 40 and 70 years carrying a gBRCAm were randomly allocated either 5 years of letrozole (2.5 mg/day) or placebo. Women with prior BC in remission for more than 5 years ago were eligible to assess the risk of second BC. Randomization was stratified by type of gBRCAm (BRCA1 versus BRCA2), previous bilateral oophorectomy, and prior BC. The primary endpoint was the 5-year incidence of invasive BC. Safety and quality of life were analyzed. RESULTS: Between 2008 and 2013, 170 women were randomized: 86 to placebo and 84 to letrozole. At 5 years, treatment adherence was 73.5 % with placebo and 76.7 % with letrozole. After a median follow-up of 72.7 months (95 % CI 71.5-78.5), the 5-year incidence of invasive BC was 13.1 % with placebo and 7.8 % with letrozole: hazard ratio, 0.70 (95 % CI 0.29-1.66), p = 0.416. Safety events and quality of life did not statistically differ in the arm. CONCLUSION: Due to the underpowered nature of the trial and the observed trend, it cannot be ruled out that using AI to prevent invasive breast cancer could be effective for BRCA1/2 carriers overall, or for specific subgroups within a larger sample size. Further randomised controlled trials are needed to determine the potential benefits of AI for gBRCA1/2m carriers.