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


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 (E(1)), estradiol (E(2)), and estrone sulfate (E(1)S) 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 E(1), E(2), and E(1)S by a mean of 81.0%, 84.9%, and 93.5%, respectively, whereas treatment with letrozole caused a corresponding decrease of 84.3%, 87.8% and 98.0%, respectively. The suppression of E(1) and E(1)S was found to be significantly better during treatment with letrozole compared with anastrozole (P =.019 and.0037, respectively).


CONCLUSIONS
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.
Geisler
Jürgen
J
Department of Oncology, Haukeland University Hospital, Bergen, Norway.
Haynes
Ben
B
Anker
Gun
G
Dowsett
Mitch
M
Lønning
Per Eystein
PE
D000368:Aged; D000077384:Anastrozole; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D018931:Antineoplastic Agents, Hormonal / Q000008:administration & dosage / Q000494:pharmacology*; D001141:Aromatase / Q000378:metabolism*; D047072:Aromatase Inhibitors; D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D018592:Cross-Over Studies; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D004958:Estradiol / Q000097:blood; D004967:Estrogens / Q000097:blood*; D004970:Estrone / Q000031:analogs & derivatives* / Q000097:blood; D005260:Female; D006801:Humans; D000077289:Letrozole; D008875:Middle Aged; D009570:Nitriles / Q000008:administration & dosage / Q000494:pharmacology*; D017698:Postmenopause; D011863:Radioimmunoassay; D014230:Triazoles / Q000008:administration & dosage / Q000494:pharmacology*
D000970:Antineoplastic Agents; D018931:Antineoplastic Agents, Hormonal; D047072:Aromatase Inhibitors; D004791:Enzyme Inhibitors; D004967:Estrogens; D009570:Nitriles; D014230:Triazoles; D004970:Estrone; D000077384:Anastrozole; D004958:Estradiol; D000077289:Letrozole; D001141:Aromatase; C017296:estrone sulfate