Contralateral Primary Tumors in Breast Cancer Patients in a Randomized Trial of Adjuvant Tamoxifen Therapy

Abstract

Prophylactic treatment with the anti-estrogen tamoxifen may reduce the risk of breast cancer because estrogens are thought to act as promotors in the pathogenesis of the disease. This article presents results on the incidence of contralateral new primary tumors among 1846 postmenopausal breast cancer patients included in a randomized trial of adjuvant tamoxifen therapy for 2 or 5 years after surgery versus no adjuvant endocrine therapy. The median follow-up was 7 years (range, 3–13 years). There was a significant reduction of contralateral breast cancer in the 931 patients in the tamoxifen group versus that in the 915 control patients (29 versus 47 cases, respectively; P =.03). The cumulative incidence at 10 years in the tamoxifen group and the control group was 5% and 8%, respectively. Analysis of the relative hazard of contralateral tumor over time showed that the benefit with tamoxifen therapy was greatest during the first 1–2 years, but there was a continued risk reduction during the entire follow-up period, i.e., more than 10 years after cessation of treatment. There was no significant difference in the number of contralateral cancers in the patients randomly assigned to 2 or 5 years of treatment, but the 95% confidence interval of the relative hazard was wide. The proportion of estrogen receptor-negative contralateral breast cancers was higher in the tamoxifen group than in the control group. There was no difference, however, between the two groups in recurrence-free survival time from the diagnosis of the contralateral cancer. The results support the initiation of controlled trials on the chemopreventive ability of tamoxifen therapy in previously healthy postmenopausal women at high risk of developing breast cancer. [J Natl Cancer Inst 83:1299–1306, 1991]