Predictive markers in elderly patients with estrogen receptor-positive breast cancer treated with aromatase inhibitors: an array-based pharmacogenetic study

Pharmacogenomics J. 2016 Nov;16(6):525-529. doi: 10.1038/tpj.2015.73. Epub 2015 Oct 27.

Abstract

So far, no reliable predictive clinicopathological markers of response to aromatase inhibitors (AIs) have been identified, and little is known regarding the role played by host genetics. To identify constitutive predictive markers, an array-based association study was performed in a cohort of 55 elderly hormone-dependent breast cancer (BC) patients treated with third-generation AIs. The array used in this study interrogates variants in 225 drug metabolism and disposition genes with documented functional significance. Six variants emerged as associated with response to AIs: three located in ABCG1, UGT2A1, SLCO3A1 with a good response, two in SLCO3A1 and one in ABCC4 with a poor response. Variants in the AI target CYP19A1 resulted associated with a favourable response only as haplotype; haplotypes with increased response association were also detected for ABCG1 and SLCO3A1. These results highlight the relevance of host genetics in the response to AIs and represent a first step toward precision medicine for elderly BC patients.

Publication types

  • Multicenter Study

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily G, Member 1 / genetics
  • ATP Binding Cassette Transporter, Subfamily G, Member 1 / metabolism
  • Age Factors
  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents, Hormonal / adverse effects
  • Antineoplastic Agents, Hormonal / therapeutic use*
  • Aromatase / genetics*
  • Aromatase / metabolism
  • Aromatase Inhibitors / adverse effects
  • Aromatase Inhibitors / therapeutic use*
  • Biomarkers, Tumor / genetics*
  • Biomarkers, Tumor / metabolism
  • Breast Neoplasms / enzymology
  • Breast Neoplasms / genetics
  • Breast Neoplasms / pathology
  • Female
  • Gene Expression Profiling / methods*
  • Glucuronosyltransferase / genetics
  • Glucuronosyltransferase / metabolism
  • Haplotypes
  • Humans
  • Italy
  • Middle Aged
  • Multidrug Resistance-Associated Proteins / genetics
  • Multidrug Resistance-Associated Proteins / metabolism
  • Oligonucleotide Array Sequence Analysis*
  • Organic Anion Transporters / genetics
  • Organic Anion Transporters / metabolism
  • Pharmacogenetics / methods*
  • Pharmacogenomic Testing / methods*
  • Pharmacogenomic Variants*
  • Phenotype
  • Precision Medicine
  • Predictive Value of Tests
  • Receptors, Estrogen / metabolism*
  • Risk Assessment
  • Risk Factors
  • Time Factors
  • Treatment Outcome

Substances

  • ABCC4 protein, human
  • ABCG1 protein, human
  • ATP Binding Cassette Transporter, Subfamily G, Member 1
  • Antineoplastic Agents, Hormonal
  • Aromatase Inhibitors
  • Biomarkers, Tumor
  • Multidrug Resistance-Associated Proteins
  • Organic Anion Transporters
  • Receptors, Estrogen
  • SLCO3A1 protein, human
  • Aromatase
  • CYP19A1 protein, human
  • Glucuronosyltransferase
  • UGT2A1 protein, human