title: Pharmacogenetic Predictors of Response.
abstract: Pharmacogenetics attempts to predict treatment response using a patient's "germline" genome as the biomarker of interest. This chapter on pharmacogenetic predictors of breast cancer response is divided into four sections. The first introduces readers to genetic variation and describes how variation in the germline genome can affect biology or pharmacology. The second section introduces the translational pathway for pharmacogenetic research and discusses the specific challenges to identifying pharmacogenetic predictors of breast cancer response. The third section is divided into three subsections, each of which discusses a distinct category of pharmacogenetic response predictors; pharmacokinetics, cancer cell sensitivity, and effector cell activation. Within each subsection a specific pharmacogenetic association is described in detail; CYP2D6-tamoxifen, BRCA-PARP inhibitors, and FCGRA-trastuzumab, respectively, followed by a general discussion of other less well-established examples or areas for further research. The chapter concludes with a summary of the current status of pharmacogenetic predictors of breast cancer response and a few predictions for the future of this field.
authors.affiliation: Department of Clinical Pharmacy, University of Michigan College of Pharmacy, 48109, Ann Arbor, MI, USA.
authors.forename: Daniel L
authors.initials: DL
authors.lastname: Hertz
authors.affiliation: Division of Hematology, Oncology, Department of Internal Medicine, University of Michigan Medical School, 48109, Ann Arbor, 6310 Cancer Center, 1500 E. Medical Center Dr.MI, USA. Jimmyrae@med.umich.edu.
authors.forename: James M
authors.initials: JM
authors.lastname: Rae
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000493:pharmacokinetics / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D001711:Biotransformation / Q000235:genetics; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D005260:Female; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing; D006801:Humans; D058990:Molecular Targeted Therapy; D018579:Patient Selection; D010597:Pharmacogenetics; D010641:Phenotype; D057285:Precision Medicine; D011237:Predictive Value of Tests; D015398:Signal Transduction / Q000187:drug effects; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor
keywords: BRCA; CYP2D6; Cancer-cell sensitivity; Effector-cell activation; FCGR; Germline polymorphism; Pharmacogenetics; Pharmacokinetic predictors