Interaction Between SNP Genotype and Efficacy of Anastrozole and Exemestane in Early-Stage Breast Cancer

Junmei Cairns, Krishna R. Kalari, James N. Ingle, Lois E. Shepherd, Matthew J. Ellis, Paul E. Goss, Poulami Barman, Erin E. Carlson, Barbara Goodnature, Matthew P. Goetz, Richard M. Weinshilboum, Huanyao Gao, Liewei Wang

Research output: Contribution to journalArticlepeer-review

Abstract

Aromatase inhibitors (AIs) are the treatment of choice for hormone receptor–positive early breast cancer in postmenopausal women. None of the third-generation AIs are superior to the others in terms of efficacy. We attempted to identify genetic factors that could differentiate between the effectiveness of adjuvant anastrozole and exemestane by examining single-nucleotide polymorphism (SNP)-treatment interaction in 4,465 patients. A group of SNPs were found to be differentially associated between anastrozole and exemestane regarding outcomes. However, they showed no association with outcome in the combined analysis. We followed up common SNPs near LY75 and GPR160 that could differentiate anastrozole from exemestane efficacy. LY75 and GPR160 participate in epithelial-to-mesenchymal transition and growth pathways, in both cases with SNP-dependent variation in regulation. Collectively, these studies identified SNPs that differentiate the efficacy of anastrozole and exemestane and they suggest additional genetic biomarkers for possible use in selecting an AI for a given patient.

Original languageEnglish (US)
JournalClinical pharmacology and therapeutics
DOIs
StateAccepted/In press - 2021

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)

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