Towards optimal endocrine therapy for hormone-sensitive breast cancer: Initial versus sequential adjuvant aromatase inhibition

Patients with hormone-receptor-positive early breast cancer have a significant risk of recurrence despite the use of adjuvant tamoxifen. The third-generation aromatase inhibitors letrozole, anastrozole, and exemestane offer promise as alternative or additional therapy to tamoxifen. As extended adjuvant therapy following completion of 5 years of tamoxifen, letrozole further decreased the risk of recurrence compared with placebo. Compared with tamoxifen, both letrozole and anastrozole significantly reduced the risk of recurrence when used as initial adjuvant therapy, and in the short term both were better tolerated than tamoxifen. Anastrozole and exemestane both reduced the risk of relapse when started after 2-3 years of tamoxifen compared with continued tamoxifen treatment; the results of letrozole in this setting are expected in 2008. These data establish adjuvant aromatase inhibitors as effective alternatives to tamoxifen. Only limited data are currently available to inform the choice between an aromatase inhibitor as either initial adjuvant therapy or sequentially after tamoxifen. Future results from the Breast International Group (BIG) 1-98 trial will further clarify strategies for the adjuvant use of aromatase inhibitors. Here, we critically review the evidence for adjuvant use of aromatase inhibitors. Comparison is made between initial aromatase inhibition, switching, and extended adjuvant strategies. Practical recommendations are given for the endocrine treatment of post-menopausal breast cancer.