Twenty-year follow-up of the Royal Marsden randomized, double-blinded tamoxifen breast cancer prevention trial.
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.
Powles
Trevor J
TJ
Parkside Oncology Clinic, 49 Parkside, Wimbledon, London SW19 5NB, UK. hdummer@parkside-hospital.co.uk
Ashley
Sue
S
Tidy
Alwynne
A
Smith
Ian E
IE
Dowsett
Mitch
M
D000328:Adult; D000368:Aged; D018931:Antineoplastic Agents, Hormonal / Q000008:administration & dosage / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000737:chemistry / Q000453:epidemiology* / Q000401:mortality / Q000517:prevention & control*; D002285:Carcinoma, Intraductal, Noninfiltrating / Q000453:epidemiology / Q000517:prevention & control; D015986:Confounding Factors, Epidemiologic; D018572:Disease-Free Survival; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D020847:Estrogen Receptor Modulators / Q000008:administration & dosage / Q000627:therapeutic use*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D015994:Incidence; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D015999:Multivariate Analysis; D016016:Proportional Hazards Models; D011960:Receptors, Estrogen / Q000032:analysis*; D018570:Risk Assessment; D012307:Risk Factors; D013629:Tamoxifen / Q000008:administration & dosage / Q000627:therapeutic use*; D013997:Time Factors; D006113:United Kingdom / Q000453:epidemiology
D018931:Antineoplastic Agents, Hormonal; D020847:Estrogen Receptor Modulators; D011960:Receptors, Estrogen; D013629:Tamoxifen