title: The implications of genetic variation for the pharmacokinetics and pharmacodynamics of aromatase inhibitors.
abstract: BACKGROUND
  Breast cancer is the most common female cancer and remains a serious public health concern worldwide. Third-generation aromatase inhibitors (AIs) are widely used in postmenopausal women with estrogen receptor positive breast cancer. However, there is marked interindividual variability in terms of the efficacy and incidence of adverse events following treatment with AIs. Pharmacogenetics has the potential to predict clinical outcomes based on patients' genetic information, paving the way towards personalized treatment.
  
  
  METHODS
  This article reviews pharmacogenetic studies of AIs, including pharmacokinetic and pharmacodynamic aspects, highlighting those studies where the efficacy and adverse events of AIs have been examined using both candidate gene and genome-wide approaches.
  
  
  CONCLUSIONS
  Pharmacogenetics is a promising approach to develop personalized medicine with AIs. However, the application of pharmacogenetics to predict therapeutic efficacy and adverse events in breast cancer patients is still far from implementation in routine clinical practice. Large, comprehensive, multicenter studies that simultaneously evaluate multiple genes and pathways, including rare variants, are warranted in order to produce reliable and informative results. The ultimate aim is to develop clinically-relevant guidelines for breast cancer therapy.
authors.affiliation: a Faculty of Pharmacy , University of Sydney , Sydney , Australia.
authors.forename: Xiaoman
authors.initials: X
authors.lastname: Liu
authors.affiliation: a Faculty of Pharmacy , University of Sydney , Sydney , Australia.
authors.forename: Siew-Kee
authors.initials: SK
authors.lastname: Low
authors.affiliation: a Faculty of Pharmacy , University of Sydney , Sydney , Australia.
authors.forename: Alan V
authors.initials: AV
authors.lastname: Boddy
mesh_terms: D018931:Antineoplastic Agents, Hormonal / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D047072:Aromatase Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D005260:Female; D014644:Genetic Variation; D006801:Humans; D010597:Pharmacogenetics / Q000379:methods; D017698:Postmenopause; D057285:Precision Medicine / Q000379:methods; D011960:Receptors, Estrogen / Q000378:metabolism
chemical_list: D018931:Antineoplastic Agents, Hormonal; D047072:Aromatase Inhibitors; D011960:Receptors, Estrogen
keywords: Aromatase inhibitors; pharmacodynamics; pharmacogenetics; pharmacokinetics