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Interaction Between SNP Genotype and Efficacy of Anastrozole and Exemestane in Early-Stage Breast Cancer
Junmei Cairns1, Krishna R Kalari2, James N Ingle3
1Division of Clinical Pharmacology, Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, Minnesota, USA.
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.
Insights
Genetic factors, specifically single-nucleotide polymorphisms (SNPs), can differentiate the effectiveness of anastrozole and exemestane in treating postmenopausal breast cancer. These findings suggest potential biomarkers for personalized AI selection.
Area of Science:
- Oncology
- Pharmacogenomics
- Genetics
Background:
- Aromatase inhibitors (AIs) are standard treatment for hormone receptor-positive early breast cancer in postmenopausal women.
- Third-generation AIs demonstrate comparable efficacy, necessitating personalized treatment selection.
- Identifying genetic factors influencing AI response is crucial for optimizing patient outcomes.
Purpose of the Study:
- To investigate single-nucleotide polymorphism (SNP)-treatment interactions to differentiate the efficacy of anastrozole versus exemestane.
- To identify potential genetic biomarkers for guiding AI selection in breast cancer patients.
Main Methods:
- Analysis of 4,465 patients treated with adjuvant anastrozole or exemestane.
- Examination of SNP-treatment interactions to identify differential associations with treatment outcomes.
- Follow-up analysis of common SNPs near LY75 and GPR160 genes.
Main Results:
- A subset of SNPs showed differential associations with outcomes between anastrozole and exemestane.
- These specific SNPs did not demonstrate an association with outcome in a combined analysis.
- SNPs near LY75 and GPR160 were identified as potentially differentiating AI efficacy, with SNP-dependent regulation of associated pathways.
Conclusions:
- Specific SNPs can differentiate the efficacy of anastrozole and exemestane in breast cancer treatment.
- LY75 and GPR160 gene regions harbor SNPs that may influence AI response.
- These findings suggest the potential utility of genetic biomarkers for personalized AI selection in breast cancer therapy.
