Twenty-year follow-up of the Royal Marsden randomized, double-blinded tamoxifen breast cancer prevention trial

J Natl Cancer Inst. 2007 Feb 21;99(4):283-90. doi: 10.1093/jnci/djk050.

Abstract

Background: 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.

Methods: 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.

Results: 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.

Conclusions: 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.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Agents, Hormonal / administration & dosage
  • Antineoplastic Agents, Hormonal / therapeutic use*
  • Breast Neoplasms / chemistry
  • Breast Neoplasms / epidemiology*
  • Breast Neoplasms / mortality
  • Breast Neoplasms / prevention & control*
  • Carcinoma, Intraductal, Noninfiltrating / epidemiology
  • Carcinoma, Intraductal, Noninfiltrating / prevention & control
  • Confounding Factors, Epidemiologic
  • Disease-Free Survival
  • Double-Blind Method
  • Drug Administration Schedule
  • Estrogen Receptor Modulators / administration & dosage
  • Estrogen Receptor Modulators / therapeutic use*
  • Female
  • Follow-Up Studies
  • Humans
  • Incidence
  • Kaplan-Meier Estimate
  • Middle Aged
  • Multivariate Analysis
  • Proportional Hazards Models
  • Receptors, Estrogen / analysis*
  • Risk Assessment
  • Risk Factors
  • Tamoxifen / administration & dosage
  • Tamoxifen / therapeutic use*
  • Time Factors
  • United Kingdom / epidemiology

Substances

  • Antineoplastic Agents, Hormonal
  • Estrogen Receptor Modulators
  • Receptors, Estrogen
  • Tamoxifen