Context: Raloxifene hydrochloride is a selective estrogen receptor modulator that has antiestrogenic effects on breast and endometrial tissue and estrogenic effects on bone, lipid metabolism, and blood clotting.

Objective: To determine whether women taking raloxifene have a lower risk of invasive breast cancer.

Design and setting: The Multiple Outcomes of Raloxifene Evaluation (MORE), a multicenter, randomized, double-blind trial, in which women taking raloxifene or placebo were followed up for a median of 40 months (SD, 3 years), from 1994 through 1998, at 180 clinical centers composed of community settings and medical practices in 25 countries, mainly in the United States and Europe.

Participants: A total of 7705 postmenopausal women, younger than 81 (mean age, 66.5) years, with osteoporosis, defined by the presence of vertebral fractures or a femoral neck or spine T-score of at least 2.5 SDs below the mean for young healthy women. Almost all participants (96%) were white. Women who had a history of breast cancer or who were taking estrogen were excluded.

Intervention: Raloxifene, 60 mg, 2 tablets daily; or raloxifene, 60 mg, 1 tablet daily and 1 placebo tablet; or 2 placebo tablets.

Main outcome measures: New cases of breast cancer, confirmed by histopathology. Transvaginal ultrasonography was used to assess the endometrial effects of raloxifene in 1781 women. Deep vein thrombosis or pulmonary embolism were determined by chart review.

Results: Thirteen cases of breast cancer were confirmed among the 5129 women assigned to raloxifene vs 27 among the 2576 women assigned to placebo (relative risk [RR], 0.24; 95% confidence interval [CI], 0.13-0.44; P<.001 to prevent case of breast cancer women would need be treated. raloxifene decreased the risk estrogen receptor-positive by ci but not receptor-negative invasive increased venous thromboembolic disease did increase endometrial>

Conclusion: Among postmenopausal women with osteoporosis, the risk of invasive breast cancer was decreased by 76% during 3 years of treatment with raloxifene.