Risk reduction of distant metastasis in hormone-sensitive postmenopausal breast cancer

Adjuvant endocrine therapy remains the principle strategy to reduce recurrence risk in postmenopausal women with early breast cancer. Studies of the natural history of breast cancer have shown that, while not reaching zero at any time point, the risk of recurrence is highest in the first 5 years following initial diagnosis and treatment. Within this initial 5 years, there is a peak of recurrence at the 2- to 3-year mark. Among the types of breast cancer recurrences observed at this early peak, distant metastasis (DM) predominates over local or contralateral relapse. DM recurrences are most strongly linked to breast-cancer-related death, and it has been suggested that adjuvant endocrine therapies that are most effective in minimizing the early peak of DM recurrence may have the most favorable impact on survival in women with early breast cancer. Aromatase inhibitors (AIs) including anastrozole, letrozole, and exemestane have gained popularity in the past few years as alternatives to 5 years of adjuvant tamoxifen, the previous standard of care. However, clinicians have not yet resolved how best to integrate AIs into breast cancer treatment; both upfront therapy (i.e., in lieu of tamoxifen) and a sequential/switch strategy (i.e., after some period of prior tamoxifen) have been proposed. The benefits and drawbacks of these approaches to AI treatment, particularly with respect to reducing early DM recurrences, are reviewed.