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Journal of Clinical Oncology, Vol 20, Issue 3 (February), 2002: 751-757
© 2002 American Society for Clinical Oncology

Influence of Letrozole and Anastrozole on Total Body Aromatization and Plasma Estrogen Levels in Postmenopausal Breast Cancer Patients Evaluated in a Randomized, Cross-Over Study

By Jürgen Geisler, Ben Haynes, Gun Anker, Mitch Dowsett, Per Eystein Lønning

From the Department of Oncology, Haukeland University Hospital, Bergen, Norway; and the Academic Department of Biochemistry, Royal Marsden Hospital, London, United Kingdom.

Address reprint requests to P.E. Lønning, MD, PhD, Department of Oncology, Haukeland University Hospital, 5021 Bergen, Norway; email: plon{at}haukeland.no

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.

Presented in part at the Thirty-Sixth Annual Meeting of the American Society of Clinical Oncology, New Orleans, LA, May 20-23, 2000.


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