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Interaction Between SNP Genotype and Efficacy of Anastrozole and Exemestane in Early‐Stage Breast Cancer
Author(s) -
Cairns Junmei,
Kalari Krishna R.,
Ingle James N.,
Shepherd Lois E.,
Ellis Matthew J.,
Goss Paul E.,
Barman Poulami,
Carlson Erin E.,
Goodnature Barbara,
Goetz Matthew P.,
Weinshilboum Richard M.,
Gao Huanyao,
Wang Liewei
Publication year - 2021
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1002/cpt.2311
Subject(s) - exemestane , anastrozole , oncology , breast cancer , single nucleotide polymorphism , medicine , aromatase inhibitor , aromatase , snp , tamoxifen , genotype , cancer , bioinformatics , biology , genetics , gene
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.