Overcoming recurrence risk: extended adjuvant endocrine therapy.

Recurrence risk after initial treatment of breast cancer is a major concern for patients. Although tamoxifen therapy has been shown to be effective in preventing recurrences and cancer-related deaths, recurrences continue to be an issue for patients after the 5-year therapy period. Until recently, there were no therapeutic options available for risk reduction in the period after the first 5 years of tamoxifen (the extended adjuvant setting). The introduction of the aromatase inhibitors (AIs), which have a different mechanism of action than tamoxifen, has provided an option for postmenopausal women seeking to extend their adjuvant hormonal treatment. The Canadian-led MA.17 trial specifically addressed this issue, and the results showed a clear, significant benefit of letrozole, improving disease-free survival over placebo among postmenopausal women who already had 5 years of adjuvant tamoxifen treatment. Because of the favorable results observed in the first interim analysis, the trial was unblinded, the patients treated with placebo were offered letrozole, and subsequently, letrozole became approved for the extended adjuvant indication. Recent analyses from MA.17 and other trials, such as the Austrian Breast and Colorectal Cancer Study Group 6a and National Surgical Adjuvant Breast and Bowel Project B-33, confirm the beneficial effect of extending adjuvant hormonal therapy with an AI and identify a large group of patients who could benefit from this therapeutic option. Recent post-unblinding analyses from the MA.17 trial have also shown that there is a benefit for patients to initiate late extended adjuvant letrozole therapy, even after a prolonged period off tamoxifen.