The role of aromatase inhibitors in the adjuvant treatment of breast carcinoma: the M. D. Anderson Cancer Center evidence-based approach

Abstract

Background: The authors examined the published evidence on the use of aromatase inhibitors (AIs) in the adjuvant setting in postmenopausal, hormone receptor-positive patients, and they provide recommendations for clinical management in 3 different situations: newly diagnosed women, women who have already received tamoxifen for 2-3 years, and women who have completed 5-years of tamoxifen and are disease free.

Methods: All double-blind, randomized, prospective studies were reviewed. Data sources included the MEDLINE data base, reviews, editorials, and experts.

Results: The Arimidex, Tamoxifen Alone or in Combination (ATAC) trial, the Intergroup Exemestane Study (IES), and the MA-17 trial confirmed the superiority of AIs over tamoxifen in women with early-stage breast carcinoma, improving disease-free survival (DFS) considerably. In the ATAC trial, the 4-year DFS rate was 86.9% on anastrozole and 84.5% on tamoxifen (P = 0.03); in the IES, the 3-year DFS rate was 91.5% on exemestane and 86.8% on tamoxifen (P = 0.00005); and, in MA-17, the 4-year estimated DFS rate was 93% on letrozole and 87% on placebo (P < or = 0.001). All studies were limited because of the immaturity of data, particularly concerning long-term safety. A negative impact on bone health was observed in all three trials. However short-term side effects were acceptable. In addition, the studies demonstrated a significant reduction in the frequency of new primary tumors in the contralateral breast.

Conclusions: Current data support anastrozole as first-line adjuvant hormonal therapy, or a change to AIs after 2-3 years of tamoxifen, or the use of letrozole at the end of a 5-year course of tamoxifen as first-choice treatment options for the management of hormone receptor-positive breast carcinoma in postmenopausal women. Ongoing clinical trials should help to define the precise timing, duration, and sequencing of AI therapy, in addition to the long-term tolerability profile and potential differences between anastrozole, letrozole, and exemestane.