Aromatase inhibitors in the management of early breast cancer.

The adjuvant treatment of patients with endocrine-sensitive breast cancer has been dominated for several decades by the gold-standard tamoxifen. Promising results on the third-generation aromatase inhibitors (AIs), anastrozole, letrozole and exemestane, in advanced disease led to the development of these agents in the treatment of early breast cancer. Recent results consistently show the superiority of these agents over tamoxifen, and the therapeutic strategies of AIs in the adjuvant setting are still being discussed. Various approaches have been evaluated, including the following: 1. upfront 5-year use of an AI instead of tamoxifen for newly diagnosed patients, 2. upfront sequence of tamoxifen followed by an AI (or the inverse) for a total of 5 years, 3. switching to an AI after 2e3 years of tamoxifen for patients presently on tamoxifen (total of 5 years), 4. extended endocrine therapy with an AI after completing 5 years of adjuvant tamoxifen. However, it is unclear whether one of these AI strategies is superior to the other ones. The overall therapeutic index of AIs appears superior to that of tamoxifen, with proven improved efficacy and a better toxicity profile. AIs are less toxic than tamoxifen in terms of thromboembolic disease and gynaecological complications, while musculoskeletal disorders and joint pains are more frequently seen with AIs. This review explores the results of all phase III adjuvant AIs trials available up to December 2007 and is trying to define the present role of AIs in the adjuvant management of postmenopausal patients with breast cancer.