Hormone receptor status has long been considered important in predicting the efficacy of endocrine agents for the treatment of breast cancer. We aim to address whether hormone receptor status influences treatment outcome in postmenopausal women receiving aromatase inhibitors for advanced breast cancer. We include data from three phase III clinical trials, comparing the activity of the new-generation aromatase inhibitors, anastrozole or letrozole, with tamoxifen as a first-line treatment. For both agents, a significant relationship was observed between hormone receptor status and time to disease progression (TTP), with increased TTP seen in patients with a higher confirmed percentage of estrogen receptor (ER)- and/or progesterone receptor (PR)-positive tumors. A relationship between objective response rate (complete or partial response) or clinical benefit (complete or partial response or stabilization for > or =24 weeks) and hormone receptor status was apparent for anastrozole but not letrozole treatment. Overall these data confirm that hormone receptor status should be a strong consideration in the selection of endocrine treatment for postmenopausal women with advanced breast cancer.