For disease-free postmenopausal women with
hormone-responsive
breast cancer, a risk for relapse remains following 5 years of adjuvant
therapy with
tamoxifen. Additional
therapy with
tamoxifen beyond 5 years is not indicated due to a demonstrated lack of efficacy beyond this time frame. Thus, there is a need for other endocrine
therapy options in the period beyond 5 years. The third-generation
aromatase inhibitors (
anastrozole,
letrozole, and
exemestane) have emerged as at least as effective and somewhat better tolerated alternatives to
tamoxifen. Three trials were initiated to evaluate the efficacy and tolerability of
aromatase inhibitors in the extended adjuvant setting. Among these, the large, double-blind, randomized, placebo-controlled MA.17 trial has already demonstrated a significant benefit of
letrozole when compared with placebo on disease-free survival in postmenopausal women previously treated for 4.5-6 years with
tamoxifen. A smaller open-label trial, the Austrian Breast and
Colorectal Cancer Study Group 6a has reported a significant benefit for
anastrozole on recurrence when used as extended adjuvant
therapy when compared with no treatment, and similar results have been seen with extended adjuvant
exemestane in the National Surgical Adjuvant Breast and Bowel Project B-33 trial. The results of these trials have important clinical implications for the future of extended adjuvant hormonal
therapy for
breast cancer.