title: Pharmacogenomics of third-generation aromatase inhibitors.
abstract: BACKGROUND
  Breast cancer is a common, life-threatening disease among women. Contemporary hormonal therapy with third-generation aromatase inhibitors for estrogen-receptor-positive breast cancers in postmenopausal women is still facing the challenge of interpatient variability in therapeutic response and intensity of adverse effects.
  
  
  METHODS
  This review highlights up-to-date literature regarding genomic findings in the literature pertaining to anastrozole, exemestane and letrozole metabolism, as well as the drug target aromatase. Genetic polymorphisms in phase I and II aromatase inhibitor metabolizing enzymes that contribute to altered responses among different patient genotypes are discussed. Similarly, aromatase CYP19A1 functional genetic polymorphisms are presented in correlation to altered aromatase activity, disease prognosis and severity of aromatase inhibitor adverse effects.
  
  
  CONCLUSIONS
  The field of pharmacogenomics has shown remarkable progress over the last few years, notably in cancer. However, large comprehensive genotyping studies, evaluated under clinical settings, are still needed to unravel the potential impact of aromatase inhibitor pharmacogenomics on breast cancer treatment, monitoring and predicting adverse effects.
authors.affiliation: University of Alberta, Faculty of Pharmacy and Pharmaceutical Sciences, 3142F Katz Group Centre for Pharmacy and Health Research, Edmonton, AB T6G 2E1, Canada.
authors.forename: Abdullah
authors.initials: A
authors.lastname: Turkistani
authors.forename: Sharon
authors.initials: S
authors.lastname: Marsh
mesh_terms: D000818:Animals; D001141:Aromatase / Q000235:genetics / Q000378:metabolism*; D047072:Aromatase Inhibitors / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics; D005260:Female; D005838:Genotype; D006801:Humans; D018579:Patient Selection; D010597:Pharmacogenetics; D010641:Phenotype; D011110:Polymorphism, Genetic; D018570:Risk Assessment; D016896:Treatment Outcome
chemical_list: D047072:Aromatase Inhibitors; D001141:Aromatase; C561410:CYP19A1 protein, human