Faculty, Staff and Student Publications
Publication Date
12-1-2024
Journal
Journal of the National Cancer Institute
Abstract
The drug's activity at the target tissue could help to define the minimal effective dose to promote cancer preventive therapy. Here we present exemestane and sex hormone concentrations within breast tissue from a presurgical study of alternative exemestane schedules. Postmenopausal women candidates for breast surgery for estrogen receptor-positive breast cancer were randomly assigned to exemestane 25 mg once daily (QD), 25 mg 3 times/week (TIW), or 25 mg per week (QW) for 4-6 weeks before surgery. Drug and sex hormones were analyzed from homogenized frozen tissue using a QTRAP 6500+ LC-MS/MS System. Tissue drug concentrations were detectable only in the QD arm with higher concentrations in nonmalignant tissue. Estradiol was nearly suppressed in all groups in the nonmalignant tissue (QD vs TIW P = .364 and QD vs QW P = .693). In contrast, a dose-response trend was observed in cancer tissue. Based on estradiol suppression in nonmalignant tissue, lower exemestane schedules should be explored for breast cancer preventive therapy. Trial Registration: Clinical Trials.gov NCT02598557 and EudraCT 2015-005063-1.
Keywords
Humans, Female, Breast Neoplasms, Androstadienes, Middle Aged, Aged, Estradiol, Biomarkers, Tumor, Postmenopause, Drug Administration Schedule, Aromatase Inhibitors, Tandem Mass Spectrometry, Receptors, Estrogen
DOI
10.1093/jnci/djae183
PMID
39110531
PMCID
PMC11630545
PubMedCentral® Posted Date
8-7-2024
PubMedCentral® Full Text Version
Post-print
Correction
Published Open-Access
yes
Included in
Bioinformatics Commons, Biomedical Informatics Commons, Medical Sciences Commons, Oncology Commons
Comments
This article has been corrected. See J Natl Cancer Inst. 2025 Jan 28;117(3):574.