A Question of Duration: Do Patients with Early-Stage Breast Cancer Need More Than Five Years of Adjuvant Endocrine Therapy?

Women with hormone receptor—positive breast cancer continue to be at risk for recurrence and mortality for many years after diagnosis. Previous clinical trials established 5 years of endocrine therapy as a standard of care for both premenopausal and postmenopausal women, resulting in long-lasting benefit over shorter durations of treatment. Until recently, trials testing durations of tamoxifen longer than 5 years have not shown additional benefit, but the ATLAS (Adjuvant Tamoxifen, Longer Against Shorter) trial, reported in 2007, showed a small but significant reduction in risk of recurrence with 10 compared with 5 years of tamoxifen therapy. Aromatase inhibitors (AIs) improve relapse-free survival (RFS) in postmenopausal women when they are used sequentially with, or replace, tamoxifen for a total of 5 years of therapy. Extension of endocrine therapy to 10 years in the National Cancer Institute of Canada Clinical Trials Group MA.17 trial demonstrated that 5 years of letrozole therapy following 5 years of tamoxifen therapy results in an improvement in RFS, but not overall survival, in postmenopausal women. Trials testing durations of AI therapy for longer than 5 years are ongoing. Selection of candidates for extended endocrine therapy should balance recurrence risk, toxicity of treatment, and comorbidities that might impact life expectancy and risk of side effects.