Tamoxifen Chemoprevention Treatment and Time to First Diagnosis of Estrogen Receptor-Negative Breast Cancer

Background Tamoxifen's effect of reducing the risk of estrogen receptor (ER)-positive breast cancer is well established. Its effect on the time to first diagnosis of breast cancer has not been reported. We used information from the randomized, placebo-controlled Breast Cancer Prevention Trial (BCPT) to make that evaluation. Methods A total of 13388 women enrolled in BCPT, of whom 174 were diagnosed with ER-positive tumors and 69 were diagnosed with ER-negative tumors. A flexible semiparametric cure rate model was used to assess the effects of tamoxifen vs placebo treatment on the time to disease diagnosis. Multivariable logistic regression, adjusted for age and tumor size at diagnosis, was used to assess the association between the mammography detection rate and treatment with tamoxifen. All statistical tests were two-sided. Results The median times to diagnosis of ER- positive tumors were similar in both treatment groups (43 months for the placebo arm and 51 months for the treatment arm). Times to diagnosis of ER- negative tumors, however, differed between treatment groups, with median times to diagnosis of 36 months in the placebo arm vs 24 months in the tamoxifen arm (difference = 12 months, 95% confidence interval [CI] = 3 to 17 months, P = .037). ER- negative breast cancers in the tamoxifen arm were more likely than those in the placebo arm to be detected by mammography than by clinical breast examination alone after adjustment for age and tumor size, but the increase was only marginally statistically significant (odds ratio for mammography detection = 4.68, 95% CI = 0.86 to 25.32, P = .073). No differences were found in the mammography detection rates for ER- positive tumors by treatment arm. Conclusion Although tamoxifen treatment does not reduce the incidence of ER- negative breast cancer, it may have advanced detection of such tumors by approximately 1 year, compared with that in the placebo arm. The time to diagnosis of ER- positive breast cancer was similar in both treatment arms.