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

Comments

This article has been corrected. See J Natl Cancer Inst. 2025 Jan 28;117(3):574.

DOI

10.1093/jnci/djae183

PMID

39110531

PMCID

PMC11630545

PubMedCentral® Posted Date

8-7-2024

PubMedCentral® Full Text Version

Post-print

djaf018.pdf (168 kB)
Correction

Published Open-Access

yes

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