A systematic review carried out on behalf of the US Agency for Healthcare Research and Quality (AHRQ) concludes that tamoxifen, raloxifene, and tibolone can reduce the risk of primary breast cancer, however all are also associated with harms and the evidence has significant limitations.

All three of these drugs have been studied as prophylaxis against primary breast cancer, however the balance of risks and harms is uncertain. This systematic review was intended to summarise the evidence. The authors carried out a literature search to January 2009 for randomised controlled trials for evidence of efficacy and including observational studies for harms. Primary outcome was reduction in breast cancer risk.

Only eight relevant controlled trials were located, seven placebo-controlled and one head to head. Analysis indicated that all three drugs reduced risk for invasive breast cancer compared with placebo: tamoxifen (risk ratio, 0.70; 95% CI, 0.59 to 0.82; 4 trials), raloxifene (risk ratio, 0.44; 95% CI, 0.27 to 0.71; 2 trials), and tibolone (risk ratio, 0.32; 95% CI, 0.13 to 0.80; 1 trial). The absolute reduction is around 7 to 10 per 1000 women per year. All drugs reduced fractures.

All drugs were associated with adverse events: tamoxifen and raloxifene increased the risk of thromboembolic events by 4 to 7 per 1000 women per year (tamoxifen > raloxifene), tamoxifen increased the risk of endometrial cancer by about 4 per 1000 women per year compared to placebo, and is associated with an increased risk of cataract compared to raloxifene. Tibolone is associated with increased risk of stroke in older women.

The authors conclude that the three drugs reduce the risk of breast cancer, but are associated with significant adverse effects. They comment that the data have significant limitations including bias, trial heterogeneity, and a dearth of head-to-head trials. Further trials are needed to clarify a number of areas.