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© The Author 2007. Published by Oxford University Press.
ARTICLES |
Twenty-Year Follow-up of the Royal Marsden Randomized, Double-Blinded Tamoxifen Breast Cancer Prevention Trial
Affiliations of authors: Parkside Oncology Clinic, London, UK (TJP); Research and Development (SA), Breast Unit (AT, IES), and Academic Department of Biochemistry (MD), Royal Marsden Hospital, London, UK; Institute of Cancer Research, London, UK (TJP, IES, MD)
Correspondence to: Trevor J. Powles, CBE, PhD, FRCP, Parkside Oncology Clinic, 49 Parkside, Wimbledon, London SW19 5NB, UK (e-mail: hdummer{at}parkside-hospital.co.uk).
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.
| CONTEXT AND CAVEATS Prior knowledge Four randomized, placebo-controlled trials, including the Royal Marsden trial, tested tamoxifen against placebo in healthy women for the prevention of breast cancer. Initial reports from these trials were inconsistent. Early results of the Royal Marsden trial found no reduction in breast cancer between tamoxifen and placebo groups. Study design Placebo-controlled, double-blinded, randomized trial. Contribution At the median follow-up, the risk of invasive breast cancer was lower in the tamoxifen group than in the placebo group but not statistically significantly so. However, during the posttreatment period, the risk of ER-positive breast cancer was statistically significantly lower in the tamoxifen group than in the placebo group. Implications Tamoxifen treatment for 8 years appears to have a long-term preventative effect against ER-positive breast cancer. Limitations This study was a small, single-institution study. Participants were younger and had a stronger family history of breast cancer than those in other trials.
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Manuscript received November 16, 2006; revised December 20, 2006; accepted January 4, 2007.
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J Natl Cancer Inst 2007 99: 257.
J Natl Cancer Inst 2007 99: 257.
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