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The role of aromatase inhibitors in the adjuvant treatment of breast carcinoma
Author(s) -
Morandi Paolo,
Rouzier Roman,
Altundag Kadri,
Buzdar Aman U.,
Theriault Richard L.,
Hortobagyi Gabriel
Publication year - 2004
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/cncr.20522
Subject(s) - medicine , exemestane , anastrozole , tamoxifen , letrozole , oncology , breast cancer , adjuvant therapy , aromatase , gynecology , placebo , cancer , pathology , alternative medicine
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 ≤ 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. Cancer 2004. © 2004 American Cancer Society.