Optimal Treatment Strategies in Hormone-Responsive Early Breast Cancer: The Role of Aromatase Inhibitors

Results from large controlled clinical trials have identified the third-generation aromatase inhibitors (AIs) as the first significant therapeutic advance in the adjuvant treatment of hormone receptor-positive (HR+) early breast cancer in postmenopausal women since the introduction of tamoxifen. Although all 3 agents, letrozole, exemestane and anastrozole, provide benefits compared with a 5-year course of tamoxifen, the optimum strategy for adjuvant AI therapy has not yet been defined. AIs have been studied upfront, in sequence with tamoxifen, in therapy switch strategies after 2-3 years of tamoxifen, and after the completion of standard adjuvant tamoxifen. Clearly, only upfront treatment with an AI can address the peak risk of relapse during the first 2-3 years after surgery, and both letrozole and anastrozole significantly reduce relapses compared with tamoxifen in this setting. Switching to exemestane or anastrozole benefits women who are disease-free following 2-3 years of tamoxifen, and women who have successfully completed the standard 5 years of tamoxifen can benefit from extended adjuvant letrozole therapy. Ongoing studies will help to determine the optimum treatment strategy, and answer other important questions, such as whether the AIs differ clinically, what influence HR expression profiles have on outcomes, and what long-term toxicities may be associated with these highly effective agents.