Overall, 2572 women were assigned to 120 mg/day raloxifene, 2557 to 60 mg/day raloxifene and 2576 to placebo. There were no significant differences at baseline between the characteristics of women in each group. Median length of follow up was 40 months (standard deviation 3 years) and a total of 1152 (22%) and 652 (25%) women had withdrawn from the raloxifene and placebo arms, respectively, by 36 months.
A total of 54 new cases of breast cancer (invasive and non-invasive types combined) were diagnosed in study participants; 22 in the 5129 women assigned to raloxifene and 32 in the 2576 assigned to placebo (relative risk [RR], 0.35; 95% confidence interval [CI], 0.21-0.58). A total of 40 new cases of invasive breast cancer were diagnosed; 13 in those assigned to raloxifene and 27 in those assigned to placebo (RR, 0.24; 95% CI, 0.13-0.44). Raloxifene was associated with a significantly lower risk of ER positive invasive breast cancer (RR, 0.10; 95% CI, 0.04-0.24) but did not have the same effect on ER negative disease (RR, 0.88; 95% CI, 0.26-3.00). Effects were similar according to dose of raloxifene.
There were 49 cases of thromboembolic disease in the raloxifene arm of the trial and 8 cases in the placebo arm (RR, 3.1; 95% CI, 1.5-6.2). In women who had undergone ultrasound examination, raloxifene treatment was associated with an increased endometrial thickness compared to placebo (P < 0.01). No overall increase in the risk of endometrial cancer was seen, although the numbers involved were small. Hot flushes (flashes), influenza-like syndromes, endometrial cavity fluid, peripheral edema, leg cramps and diabetes were all reported significantly more frequently in the raloxifene compared to the placebo group. Hypertension, hypercholesterolamia, hematuria and bradycardia were all reported significantly less frequently in the raloxifene group. Overall mortality did not differ between the placebo (1.0%) and combined raloxifene group (0.8%).