The role of aromatase inhibitors in the adjuvant treatment of breast carcinoma: the M. D. Anderson Cancer Center evidence-based approach.
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.
Morandi
Paolo
P
Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston 77030, USA.
Rouzier
Roman
R
Altundag
Kadri
K
Buzdar
Aman U
AU
Theriault
Richard L
RL
Hortobagyi
Gabriel
G
D000077384:Anastrozole; D000730:Androstadienes / Q000008:administration & dosage / Q000627:therapeutic use*; D018931:Antineoplastic Agents, Hormonal / Q000008:administration & dosage / Q000627:therapeutic use*; D047072:Aromatase Inhibitors; D001943:Breast Neoplasms / Q000188:drug therapy*; D017024:Chemotherapy, Adjuvant; D018572:Disease-Free Survival; D004311:Double-Blind Method; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D019317:Evidence-Based Medicine; D005260:Female; D006801:Humans; D000077289:Letrozole; D009376:Neoplasms, Hormone-Dependent / Q000188:drug therapy; D009570:Nitriles / Q000008:administration & dosage / Q000627:therapeutic use*; D017698:Postmenopause; D011446:Prospective Studies; D013629:Tamoxifen / Q000008:administration & dosage; D014230:Triazoles / Q000008:administration & dosage / Q000627:therapeutic use*
D000730:Androstadienes; D018931:Antineoplastic Agents, Hormonal; D047072:Aromatase Inhibitors; D004791:Enzyme Inhibitors; D009570:Nitriles; D014230:Triazoles; D013629:Tamoxifen; D000077384:Anastrozole; D000077289:Letrozole; C056516:exemestane