title: Actionable pharmacogenetic markers for prediction and prognosis in breast cancer.
abstract: Breast cancer is a heterogeneous disease that necessitates proper patient classification to direct surgery, pharmacotherapy, and radiotherapy. Despite patients within the same subgroup receiving similar pharmacotherapy, substantial variation in clinical outcomes is observed. Pharmacogenetic variations with direct effect on pharmacokinetics and pharmacodynamics play a central role in clinical outcomes. Pharmacogenetic markers associated with clinical outcome are known as biomarkers. They are termed prognostic biomarkers when their presence is associated with a specific clinical outcome. If the presence of such biomarkers guides treatment, they are termed predictive biomarkers. A number of pharmacogenetic markers have been described in relation to breast cancer pharmacotherapy both in the adjuvant and neoadjuvant setting. CYP2D6 allelic variants produce variable rates of tamoxifen metabolism and are associated with survival outcomes. Other biomarkers have been described in relation to other forms of endocrine therapy and trastuzumab. In neoadjuvant and adjuvant breast cancer chemotherapy, specific biomarkers were correlated with clinical outcomes and risk of drug toxicity. This review highlights key biomarkers in breast cancer pharmacotherapy with the potential of translating such study outcomes into clinical practice.
authors.affiliation: Department of Pathology, University of Malta, Msida, MSD2090 Malta.
authors.forename: Keith
authors.initials: K
authors.lastname: Sacco
authors.affiliation: Department of Pathology, University of Malta, Msida, MSD2090 Malta.
authors.forename: Godfrey
authors.initials: G
authors.lastname: Grech
keywords: Aromatase inhibitor; Breast cancer; Genotypes; Pharmacogenetics; Predictive preventive personalized medicine; Tamoxifen; Therapy resistance; Trastuzumab