OBJECTIVE: Tamoxifen has been at the foundation of adjuvant treatment to prevent disease recurrence in postmenopausal women with hormone-responsive early breast cancer. After 5 years of adjuvant tamoxifen therapy, however, options for further treatment are limited. Additional tamoxifen is not indicated, as no further benefit in disease-free survival (DFS) has been observed. The aromatase inhibitor letrozole significantly improves DFS over placebo in postmenopausal women who have completed 4.5-6.0 years of adjuvant tamoxifen. MATERIALS AND METHODS: This article reviews the data supporting extended adjuvant letrozole therapy. CONCLUSIONS: Extended adjuvant letrozole has been shown to be particularly effective in patients with node-positive disease, who are at a higher risk for disease recurrence, improving both DFS and overall survival. Extended adjuvant letrozole is associated with a significant increase in self-reported osteoporosis, but no significant increases in fracture, endometrial malignancies, hypercholesterolemia, or cardiovascular events and no worsening of quality of life, making it suitable for long-term use. The ASCO treatment guidelines recommend at least 2.5 years of extended adjuvant letrozole for patients completing tamoxifen therapy, based upon the MA.17 trial follow-up period. A recent cohort analysis now suggests that extended adjuvant letrozole treatment for at least 48 months is associated with greater benefit. The efficacy of letrozole for up to 10 years following tamoxifen is also being investigated.
