Delayed adjuvant tamoxifen:: Ten-year results of a collaborative randomized controlled trial in early breast cancer (TAM-02 trial)

Aim: Immediate adjuvant tamoxifen reduces disease recurrence and improves survival in patients with early breast cancer. However, is it too late to administer tamoxifen to patients who have already undergone treatment, but were unable to benefit from this adjuvant therapy? The French National Cancer Centers (FNCLCC) have investigated the efficacy of delayed tamoxifen administration in a randomized controlled trial. Patients and methods: From September 1986 to October 1989, women with primary breast cancer, who had undergone surgery, radiotherapy, and/or received adjuvant chemotherapy but not hormone therapy more than two years earlier, were randomized to receive either 30 mg/day tamoxifen or no treatment. The 10-year disease-free and overall survival rates of the two groups of patients and of various subgroups were determined according to the Kaplan-Meyer method and compared by the log-rank test. Results: This intention-to-treat analysis comprised 250 women in the tamoxifen group and 244 in the control group. Patient characteristics (age, T stage, number of positive nodes, receptor status, and interval since tumor treatment) were comparable in both groups. Delayed adjuvant tamoxifen significantly improved overall survival only in node-positive patients and in patients with estrogen receptor-positive (ER+) or progesterone receptor-positive (PR+) tumors. Disease-free survival, however, was significantly improved in the global population and in several patient subgroups (node-positive, ER+, PR+). Patients in whom the interval between primary treatment and delayed adjuvant tamoxifen was greater than five years also had significantly improved disease-free survival. Conclusions: Overall and disease-free survival results indicate that delayed adjuvant tamoxifen administration (30 mg/day) is justified in women with early breast cancer, even if this treatment is initiated two or more years after primary treatment.