Aromatase inhibitors: changing the face of endocrine therapy for breast cancer

Tamoxifen has provided the mainstay of endocrine therapy for more than 20 years. However, the development of the third-generation aromatase inhibitors (AIs), anastrozole, letrozole and exemestane, has provided an alternative strategy for managing hormone-responsive breast cancer in postmenopausal women. The efficacy of the AIs as first- and second-line treatment for advanced disease has been demonstrated in several double-blind, randomised trials and they are now widely accepted in this setting. More recently evidence has emerged supporting the role of aromatase inhibitors in early breast cancer, either as 5 years of initial adjuvant therapy or following 2.5 or 5 years of tamoxifen as part of a switching strategy. Controversy remains over which is the optimal treatment strategy, due to a lack of trials directly comparing initial adjuvant therapy with switching. Nevertheless, the data indicate that the third-generation AIs provide superior recurrence benefits to tamoxifen in the adjuvant setting. In addition, the tolerability profiles of the AIs appear to be more acceptable than tamoxifen, with a reduction in serious adverse events such as endometrial cancer and thromboembolic events associated with the AIs compared with tamoxifen. Ongoing trials aim to clarify the role of the AIs in preoperative treatment and chemoprevention.