Switching to Anastrozole Versus Continued Tamoxifen Treatment of Early Breast Cancer: Preliminary Results of the Italian Tamoxifen Anastrozole Trial

Purpose Tamoxifen, which is actually the gold standard adjuvant treatment in estrogen receptor–positive early breast cancer, is associated with an increased risk of endometrial cancer and other life-threatening events. Moreover, many women relapse during or after tamoxifen therapy because of the development of resistance. Therefore new approaches are required. Patients and Methods We conducted a prospective randomized trial to test the efficacy of switching postmenopausal patients who were already receiving tamoxifen to the aromatase inhibitor anastrozole. After 2 to 3 years of tamoxifen treatment, patients were randomly assigned either to receive anastrozole 1 mg/d or to continue receiving tamoxifen 20 mg/d, for a total duration of treatment of 5 years. Disease-free survival was the primary end point. Event-free survival, overall survival, and safety were secondary end points. Results Four hundred forty-eight patients were enrolled. All women had node-positive, estrogen receptor–positive tumors. At a median follow-up time of 36 months, 45 events had been reported in the tamoxifen group compared with 17 events in the anastrozole group (P = .0002). Disease-free and local recurrence-free survival were also significantly longer in the anastrozole group (hazard ratio [HR] = 0.35; 95% CI, 0.18 to 0.68; P = .001 and HR = 0.15; 95% CI, 0.03 to 0.65; P = .003, respectively). Overall, more adverse events were recorded in the anastrozole group compared with the tamoxifen group (203 v 150, respectively; P = .04). However, more events were life threatening or required hospitalization in the tamoxifen group than in the anastrozole group (33 of 150 events v 28 of 203 events, P = .04). Conclusion Switching to anastrozole after the first 2 to 3 years of treatment is well tolerated and significantly improves event-free and recurrence-free survival in postmenopausal patients with early breast cancer.