Incidence of invasive breast cancer following 8 years of raloxifene therapy in postmenopausal women with osteoporosis: Results from the Continuing Outcomes Relevant to Evista (CORE) trial

Abstract

1000 Background: Raloxifene (RLX) is approved for prevention and treatment of postmenopausal osteoporosis. Breast cancer incidence was a secondary outcome of the Multiple Outcomes of Raloxifene (MORE) trial; compared to placebo, invasive breast cancer (IBC) incidence was reduced 72% in postmenopausal women with osteoporosis receiving RLX for 4 yrs. Methods: The primary aim of CORE, a 4-yr double-blind follow-up to MORE, was to examine the effect of long-term (8 yrs) therapy with RLX on incidence of IBC by continuing observation of women randomized in MORE. Time to first IBC was the primary endpoint and time to first estrogen-receptor (ER) positive IBC was a secondary outcome. All MORE participants were eligible for CORE. CORE participants randomized to placebo in MORE continued to receive placebo in CORE. Those randomized to RLX 60mg/d or 120 mg/d during MORE received RLX 60 mg/d in CORE. Comparisons between the two therapy groups were made using a Cox proportional hazards model and a log-rank test. Results: The primary analysis dataset for CORE included 5213 MORE participants (RLX 60 mg/d, n=3510; placebo, n=1703). For the CORE primary analysis, there were 61 cases of adjudicated breast cancer (31 [0.9%] RLX, 30 [1.8%] placebo) and 52 were IBC (24 [0.7%] RLX, 28 [1.6%] placebo). Compared to placebo, a 59% reduction in IBC incidence was reported in the RLX group (hazard ratio [HR] 0.41, 95% CI 0.24, 0.71; p < 0.001). ER status was determined for 46 IBC cases. Compared to placebo, incidence of invasive ER-positive breast cancer was also decreased in the RLX group (HR 0.34, 95% CI 0.18, 0.66; p < 0.001). The incidence of ER-negative breast cancer was not altered by RLX therapy (HR 1.13, 95% CI 0.29, 4.35). Conclusions: When combined with the statistically significant reduction in incidence of IBC observed in the MORE trial, the CORE results provide additional evidence that the incidence of invasive breast cancer, specifically ER-positive invasive breast cancer, continues to be significantly reduced in postmenopausal women with osteoporosis through 8 years of therapy with raloxifene. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Eli Lilly & Co. Eli Lilly & Co.; Neothermia, Inc. Eli Lilly & Co.; Neothermia, Inc. Eli Lilly & Co. Eli Lilly & Co.; Pfizer; Organon; NIH; DaCosta Fund for Prevention of Breast Cancer; Merck Eli Lilly & Co. Eli Lilly & Co.