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Letrozole Suppresses Plasma Estradiol and Estrone Sulphate More Completely Than Anastrozole in Postmenopausal Women With Breast Cancer

J. Michael Dixon, Lorna Renshaw, Oliver Young, Juliette Murray, E. Jane Macaskill, Mary McHugh, Elizabeth Folkerd, David A. Cameron, Roger P. A'Hern, Mitch Dowsett

From the Edinburgh Breast Unit and Department of Oncology, Western General Hospital, Edinburgh; Academic Department of Biochemistry, Royal Marsden Hospital, London; and the Institute of Cancer Research Clinical Trials and Statistics Unit, Sutton, United Kingdom

Corresponding author: J. Michael Dixon, MD, Edinburgh Breast Unit, Western General Hospital, Edinburgh EH4 2XU, United Kingdom; e-mail: jmd{at}ed.ac.uk

Purpose: To compare the effects of anastrozole and letrozole on plasma estradiol (E2) and estrone sulfate (E1S) levels.

Patients and Methods: Fifty-four postmenopausal women with estrogen receptor–positive breast cancer receiving aromatase inhibitors (AIs) as part of their adjuvant therapy were randomly assigned to receive either 3 months of anastrozole (1 mg) followed by 3 months of letrozole (2.5 mg), both given orally once daily, or 3 months of the opposite sequence. Blood was taken at the same time and the same day of the week from each patient, before and after 3 months of each drug, and plasma levels of E2 and E1S were determined using highly sensitive radioimmunoassays.

Results: There were 27 patients in each group. The mean age of the patients was 63 years (range, 49 to 83 years). Baseline E2 levels ranged from 3 pmol/L to 91 pmol/L with a mean of 25.7pmol/L. Only one of 54 (2%) patients had an E2 value 3 pmol/L after receiving letrozole, versus 20 of 54 (37%) patients after receiving anastrozole (P < .001). Extrapolation revealed a mean E2 level after anastrozole treatment of 2.71 pmol/L (range, 2.38 to 3.08 pmol/L). Following letrozole, it was 1.56 pmol/L (range, 1.37 to 1.78 pmol/L). Mean residual E2 was 10.1% for anastrozole and 5.9% for letrozole. Residual E1S levels were 4.6% for anastrozole and 2.0% for letrozole (P = .001).

Conclusion: Letrozole reduces plasma E2 and E1S levels to a significantly greater extent than anastrozole in postmenopausal women taking AIs as part of their adjuvant therapy for hormone receptor–positive breast cancer.

Supported by an unrestricted educational grant from Novartis.

Presented in part at the American Society of Clinical Oncology 2006 Annual Meeting, June 2-6, 2006, Atlanta, GA; in poster format at the European Society for Medical Oncology 31st ESMO Congress,September 29-October 3, 2006, Istanbul, Turkey; and at San Antonio Breast Cancer Symposium, December 14-17, 2006, San Antonio, TX.

Authors’ disclosures of potential conflicts of interest and author contributions are found at the end of this article.