Benefits
Tamoxifen is a selective estrogen receptor modulator (SERM), the first FDA-approved agent specifically for breast cancer risk reduction.
STAR trial (P-2), comparing tamoxifen directly against raloxifene, ~19,000 women, 5 years treatment, 81-month median follow-up: both drugs reduced invasive breast cancer risk substantially, with raloxifene retaining about 76% of tamoxifen's effectiveness (risk ratio 1.24 favoring tamoxifen). Vogel et al., Cancer Prev Res, 2010 Earlier placebo-controlled trials (over 25,000 women) found tamoxifen reduced breast cancer risk by roughly 40%.
Side Effects
The real reason tamoxifen didn't gain wide acceptance for prevention use, despite being first-to-market: it significantly increases endometrial cancer and thromboembolic (blood clot) risk compared to raloxifene. In the STAR trial specifically, raloxifene showed significantly lower endometrial cancer risk (RR 0.55, P=0.003), lower uterine hyperplasia (RR 0.19), and lower thromboembolic events (RR 0.75) than tamoxifen — see Raloxifene's page for the direct comparison. This is a real, clinically significant safety tradeoff, not a minor side-effect footnote.
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