The role of aromatase inhibitors in the adjuvant treatment of breast carcinoma

The M. D. Anderson Cancer Center evidence-based approach

Authors

  • Paolo Morandi M.D.,

    1. Department of Breast Medical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas
    2. Department of Oncology, S. Bortolo Hospital, Vicenza, Italy
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  • Roman Rouzier M.D.,

    1. Department of Breast Medical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas
    2. Breast Cancer Unit, Institut Gustave Roussy, Villejuif Cedex, France
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  • Kadri Altundag M.D.,

    1. Department of Breast Medical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas
    2. Department of Medical Oncology, Hacettepe University, Faculty of Medicine, Ankara, Turkey
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  • Aman U. Buzdar M.D.,

    Corresponding author
    1. Department of Breast Medical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas
    • Department of Breast Medical Oncology, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Boulevard, Unit 424, Houston, TX 77030
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    • Fax: (713) 794-4385

  • Richard L. Theriault D.O.,

    1. Department of Breast Medical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas
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  • Gabriel Hortobagyi M.D.

    1. Department of Breast Medical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas
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  • The following faculty members participated in the development of this article: Banu Arun, M.D.; Daniel Booser, M.D.; Massimo Cristofanilli, M.D.; Francisco J. Esteva, M.D., Ph.D.; Ana M. Gonzalez-Angulo, M.D.; Sharon Giordano, M.D.; Marjorie Green, M.D.; Karin Gwyn, M.D.; Nuhad Ibrahim, M.D.; James L. Murray, M.D.; Lajos Pusztai, M.D., Ph.D.; Edgardo Rivera, M.D.; Eva Thomas, M.D.; Vicente Valero, M.D.; Ronald Walters, M.D. (Department of Breast Medical Oncology, University of Texas M. D. Anderson Cancer Center, Houston, Texas); Robert Bast, M.D. (Department of Gynecologic Oncology, University of Texas M. D. Anderson Cancer Center, Houston Texas); Therese Bevers, M.D.; Abenaa Brewster, M.D. (Department of Cancer Prevention, University of Texas M. D. Anderson Cancer Center, Houston, Texas); Thomas Buchholz, M.D.; Marsha McNeese, M.D.; Eric Strom, M.D. (Department of Radiation Oncology, University of Texas M. D. Anderson Cancer Center, Houston, Texas).

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.

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