MORE Trial

The effect of raloxifene hydrochloride on the incidence of breast cancer was assessed as a secondary safety endpoint in a randomized, placebo-controlled, double-blind, multinational osteoporosis treatment trial in postmenopausal women [ see Clinical Studies ( 14.1) ]. After 4 years, raloxifene hydrochloride, 60 mg administered once daily, reduced the incidence of all breast cancers by 62%, compared with placebo (HR 0.38, 95% CI 0.22 to 0.67). Raloxifene hydrochloride reduced the incidence of invasive breast cancer by 71%, compared with placebo (ARR 3.1 per 1000 women-years); this was primarily due to an 80% reduction in the incidence of ER-positive invasive breast cancer in the raloxifene hydrochloride group compared with placebo. Table 7 presents efficacy and selected safety outcomes .

CORE Trial

The effect of raloxifene hydrochloride on the incidence of invasive breast cancer was evaluated for 4 additional years in a follow-up study conducted in a subset of postmenopausal women originally enrolled in the MORE osteoporosis treatment trial. Women were not re-randomized; the treatment assignment from the osteoporosis treatment trial was carried forward to this study. Raloxifene hydrochloride, 60 mg administered once daily, reduced the incidence of invasive breast cancer by 56%, compared with placebo (ARR 3.0 per 1000 women-years); this was primarily due to a 63% reduction in the incidence of ER-positive invasive breast cancer in the raloxifene hydrochloride group compared with placebo. There was no reduction in the incidence of ER-negative breast cancer. In the osteoporosis treatment trial and the follow-up study, there was no difference in incidence of noninvasive breast cancer between the raloxifene hydrochloride and placebo groups. Table 7 presents efficacy and selected safety outcomes .

In a subset of postmenopausal women followed for up to 8 years from randomization in MORE to the end of CORE, raloxifene hydrochloride, 60 mg administered once daily, reduced the incidence of invasive breast cancer by 60% in women assigned raloxifene hydrochloride (N = 1355) compared with placebo (N = 1286) (HR 0.40, 95% CI 0.21, 0.77; ARR 1.95 per 1000 women-years); this was primarily due to a 65% reduction in the incidence of ER-positive invasive breast cancer in the raloxifene hydrochloride group compared with placebo .

RUTH Trial

The effect of raloxifene hydrochloride on the incidence of invasive breast cancer was assessed in a randomized, placebo-controlled, double-blind, multinational study in 10,101 postmenopausal women at increased risk of coronary events. Women in this study had a median age of 67.6 years (range 55 to 92) and were followed for a median of 5.6 years (range 0.01 to 7.1). Eighty-four percent were White, 9.8% of women reported a first-degree relative with a history of breast cancer, and 41.4% of the women had a 5-year predicted risk of invasive breast cancer ≥ 1.66%, based on the modified Gail model.

Raloxifene hydrochloride, 60 mg administered once daily, reduced the incidence of invasive breast cancer by 44% compared with placebo [absolute risk reduction (ARR) 1.2 per 1000 women-years]; this was primarily due to a 55% reduction in estrogen receptor (ER)-positive invasive breast cancer in the raloxifene hydrochloride group compared with placebo (ARR 1.2 per 1000 women-years). There was no reduction in ER-negative invasive breast cancer. Table 8 presents efficacy and selected safety outcomes. 

The effect of raloxifene hydrochloride in reducing the incidence of invasive breast cancer was consistent among women above or below age 65 or with a 5-year predicted invasive breast cancer risk, based on the modified Gail model, < 1.66%, or ≥ 1.66%.