Background: Trials demonstrate the efficacy of medications to reduce the risk for invasive breast cancer.
Purpose: To summarize benefits and harms of tamoxifen citrate, raloxifene, and tibolone to reduce the risk for primary breast cancer.
Data Sources: MEDLINE and Cochrane databases from inception to January 2009, Web of Science, trial registries, and manufacturer information.
Study Selection: Predefined eligibility criteria were used to select articles. English-language reports of randomized, controlled trials (RCTs) for benefits and RCTs and observational studies for harms were included.
Data Extraction: Two reviewers assessed study data, quality, and applicability.
Data Synthesis: Seven placebo-controlled RCTs and 1 head-to-head trial provide results for main outcomes. Tamoxifen (risk ratio, 0.70 [95% CI, 0.59 to 0.82]; 4 trials), raloxifene (risk ratio, 0.44 [CI, 0.27 to 0.71]; 2 trials), and tibolone (risk ratio, 0.32 [CI, 0.13 to 0.80]; 1 trial) reduce risk for invasive breast cancer compared with placebo by 7 to 10 per 1000 women per year. Tamoxifen and raloxifene reduce estrogen receptorâ€“positive breast cancer but not estrogen receptorâ€“negative breast cancer, noninvasive breast cancer, or mortality. All medications reduce fractures. Tamoxifen (risk ratio, 1.93 [CI, 1.41 to 2.64]; 4 trials) and raloxifene (risk ratio, 1.60 [CI, 1.15 to 2.23]; 2 trials) increase thromboembolic events by 4 to 7 per 1000 women per year; raloxifene causes fewer events than tamoxifen. Tamoxifen increases risk for endometrial cancer (risk ratio, 2.13 [CI, 1.36 to 3.32]; 3 trials) compared with placebo by 4 per 1000 women per year and causes cataracts compared with raloxifene. Tibolone causes strokes in older women.
Limitations: Bias, trial heterogeneity, and a dearth of head-to-head trials limit this review. Data are lacking on doses, duration, and timing of the medications; long-term effects; and nonwhite and premenopausal women.
Conclusion: Three medications reduce risk for primary breast cancer but increase risk for thromboembolic events (tamoxifen, raloxifene), endometrial cancer (tamoxifen), or stroke (tibolone).
Primary Funding Source: Agency for Healthcare Research and Quality.