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The third-generation aromatase inhibitor letrozole offers a promising approach to treating hormone-sensitive breast cancer for postmenopausal women, through potent and specific inhibition of estrogen synthesis. In neoadjuvant and first-line treatment, letrozole demonstrated superior efficacy compared with tamoxifen in randomized Phase III trials. Initial results of Breast InterGroup 1-98, a large ongoing randomized trial investigating primary adjuvant endocrine treatment with either letrozole or tamoxifen, have recently been presented. Patients treated with letrozole demonstrated a 19% improvement in disease-free survival and a significant reduced risk of distant recurrences, holding out the prospect of a survival advantage over tamoxifen treatment with further maturation of the trial. For patients who have already completed 5 years of tamoxifen, extended endocrine therapy with letrozole is a new therapeutic option based on the results of the MA-17 trial. The optimal use of aromatase inhibitors remains an open question, at least until results from randomized trials (BIG 1-98, TEAM) investigating the sequential use of an aromatase inhibitor and tamoxifen in comparison with continuous monotherapy become available.