PURPOSE: To compare the effects of the two novel, potent, nonsteroidal aromatase inhibitors anastrozole and letrozole on total-body aromatization and plasma estrogen levels.

PATIENTS AND METHODS: Twelve postmenopausal women with estrogen receptor–positive, metastatic breast cancer were treated with anastrozole 1 mg orally (PO) and letrozole 2.5 mg PO once daily, each given for a time interval of 6 weeks in a randomized sequence. Total-body aromatization was determined before treatment and at the end of each treatment period using a dual-label isotopic technique involving isolation of the metabolites with high-performance liquid chromatography. Plasma levels of estrone (E₁), estradiol (E₂), and estrone sulfate (E₁S) were determined in samples obtained before each injection using highly sensitive radioimmunoassays.

RESULTS: Pretreatment aromatase levels ranged from 1.68% to 4.27%. On-treatment levels of aromatase were detectable in 11 of 12 patients during treatment with anastrozole (mean percentage inhibition in the whole group, 97.3%) but in none of the 12 patients during treatment with letrozole (> 99.1% suppression in all patients; Wilcoxon, P = .0022, comparing the two drug regimens). Treatment with anastrozole suppressed plasma levels of E₁, E₂, and E₁S by a mean of 81.0%, 84.9%, and 93.5%, respectrively, whereas treatment with letrozole caused a corresponding decrease of 84.3%, 87.8% and 98.0%, respectively. The suppression of E₁ and E₁S was found to be significantly better during treatment with letrozole compared with anastrozole (P = .019 and .0037, respectively).

CONCLUSION: This study revealed letrozole (2.5 mg once daily) to be a more potent suppressor of total-body aromatization and plasma estrogen levels compared with anastrozole (1 mg once daily) in postmenopausal women with metastatic breast cancer.