Abstract
Raloxifene is a selective estrogen receptor modulator (SERM) that has estrogenic effects on bone, blood clotting, and lipid metabolism and antiestrogenic effects on the breast and endometrium. The Multiple Outcomes of Raloxifene Evaluation study, a multicenter, randomized, double-blind trial, assessed the effects of raloxifene in 7705 postmenopausal women aged ≤80 years (average age, 66.5 years) who had osteoporosis (defined as vertebral fractures or a T score at least 2.5 SDs below the mean for young healthy women at the femoral neck or spine). Nearly all participants were white. None had a history of breast cancer or were taking estrogen. They received raloxifene in tablet form in a daily dose of 60 or 120 mg or placebo tablets and were followed for a median of 40 months. Roughly two-thirds of women in the study were assigned to receive raloxifene. Nearly 1800 women had transvaginal ultrasonography.Breast cancer was found in four women during follow-up. The relative risk (RR) of invasive breast cancer in raloxifene-treated women was 0.24. When all confirmed breast cancers were included, the RR was 0.35. Comparable effects were achieved with the two doses of raloxifene. Only the risk of estrogen receptor–positive cancer was lowered. Side effects seen more frequently in treated women included hot flashes, flu-like symptoms, fluid in the endometrial cavity, peripheral edema, and leg cramps. Deep venous thrombosis and pulmonary embolism also were more frequent in treated women, as was new or worsening diabetes. In contrast, hypertension, hypercholesterolemia, hematuria, and bradycardia were more frequent in placebo recipients. Endometrial thickness tended to increase slightly over time in raloxifene-treated women and to decrease in the placebo group. Two women in each group developed endometrial carcinoma. Raloxifene treatment for osteoporosis seems to lower the risk that breast cancer will develop in postmenopausal women.JAMA 1999;281:2189–2197