Twenty-Year Follow-up of the Royal Marsden Randomized, Double-Blinded Tamoxifen Breast Cancer Prevention Trial

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Several clinical trials have reported an early reduction in breast cancer incidence in healthy women using tamoxifen to reduce their risk of breast cancer but have not reported longer follow-up data for the evaluation of breast cancer prevention. We report the blinded 20-year follow-up (median follow-up=13 years) of the Royal Marsden trial to identify any long-term prevention of breast cancer associated with tamoxifen treatment.


We randomly assigned 2494 healthy women to oral tamoxifen (20 mg/day) or placebo for 8 years. The primary outcome was occurrence of invasive breast cancer. A secondary planned analysis of estrogen receptor (ER)–positive invasive breast cancer was also done. Survival was assessed by use of a Cox proportional hazards model in both univariate and multivariable analyses. The durability of the treatment effect was assessed by use of a Cox regression analysis. All statistical tests were two-sided.


Among the 2471 eligible participants (1238 participants in the tamoxifen arm and 1233 participants in the placebo arm), 186 developed invasive breast cancer (82 on tamoxifen and 104 on placebo; hazard ratio [HR]=0.78, 95% confidence interval [CI]=0.58 to 1.04; P=.1). Of these 186 cancers, 139 were ER positive (53 on tamoxifen and 86 on placebo; HR=0.61, 95% CI=0.43 to 0.86; P=.005). The risk of ER-positive breast cancer was not statistically significantly lower in the tamoxifen arm than in the placebo arm during the 8-year treatment period (30 cancers in the tamoxifen arm and 39 in the placebo arm; HR=0.77, 95% CI=0.48 to 1.23; P=.3) but was statistically significantly lower in the posttreatment period (23 in the tamoxifen arm and 47 in the placebo arm; HR=0.48, 95% CI=0.29 to 0.79; P=.004). Fifty-four participants in each arm have died from any cause (HR=0.99, 95% CI=0.68 to 1.44; P=.95). The adverse event profiles for both arms were similar to those previously reported and occurred predominantly during the treatment period.


A statistically significant reduction in the incidence of ER-positive breast cancer was observed in the tamoxifen arm that occurred predominantly during the post treatment follow-up, indicating long-term prevention of estrogen-dependent breast cancer by tamoxifen.

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