Aromatase inhibitors in adjuvant therapy for hormone receptor positive breast cancer: A systematic review

BACKGROUND: A systematic review was undertaken to review the evidence for the use of third-generation aromatase inhibitors (anastrozole, letrozole and exemestane) as adjuvant therapy for post-menopausal women with early-stage, hormone receptor-positive breast cancer and to develop and support recommendations for their use, with regard to three areas: aromatase inhibitors compared to tamoxifen, aromatase inhibitors in sequence with tamoxifen for a total of five years, and aromatase inhibitors given after five years of tamoxifen therapy. METHODS: MEDLINE, EMBASE, American Society of Clinical Oncology and San Antonio Breast Cancer Symposium proceedings, and the Cochrane Library were searched to May 2007 for reports of randomized controlled trials that met the inclusion criteria. RESULTS: Nine randomized controlled trials and one meta-analysis of three of these trials were identified that reported efficacy data. Eight of these trials reported significantly improved disease-free survival in the arms that involved aromatase inhibitors. The meta-analysis reported significantly improved overall survival among all patients, as did one individual trial. One trial of five years letrozole or placebo after five years tamoxifen found improved overall survival among node-positive patients. CONCLUSIONS: Aromatase inhibitors provide an alternative to tamoxifen as adjuvant therapy for post-menopausal, hormone-receptor-positive breast cancer patients. The options include anastrozole and letrozole for five years, as well as anastrozole and exemestane following two to three years of tamoxifen, for a total five years of hormonal therapy. Five years of letrozole should be considered following five years of tamoxifen. Patients receiving aromatase inhibitors should be monitored for changes in bone mineral density and for cardiovascular disease risk factors and outcomes.