Abstract

After local therapy, women with early breast cancer remain at risk of recurrence for an extended period. For women with hormone-receptor-positive (HR+) disease, the risk of relapse peaks in the first 2-3 years after surgery. Distant metastases, which are associated with a high risk of death from breast cancer, account for the majority of relapses, both early and late. Preventing distant metastases is therefore a primary aim of systemic adjuvant treatment. Tamoxifen was the mainstay of endocrine adjuvant treatment for HR+ disease, but despite its proven benefits, a significant proportion of patients will relapse while on tamoxifen therapy. The third-generation aromatase inhibitors (AIs)--letrozole, anastrozole, and exemestane--have recently replaced tamoxifen as the recommended adjuvant endocrine therapy, on the basis of greater efficacy and better tolerability. However, the optimal use of AIs in the adjuvant setting requires further investigation, including identification of the best treatment strategy. Although a switching strategy does reduce relapses, only upfront AI therapy can address the early peak of distant recurrences that occur despite tamoxifen. Similarly, only upfront AI therapy can avoid the life-threatening side effects that occur in the early years of tamoxifen therapy. Available evidence supports a hypothesis that upfront adjuvant AI therapy is the most appropriate treatment strategy for postmenopausal patients with HR+ disease. Definitive evidence awaits results from ongoing randomized trials.