Pharmacodiagnostic testing in breast cancer: focus on HER2 and trastuzumab therapy.
Pharmacogenomics is defined as research into inherited genetic variations that determine an individual's response to therapeutic agents. In oncology, pharmacogenomics based on somatic molecular alterations inherited by subsequent cancer cell generations forms the basis of molecular targeting of novel therapeutic agents. What has emerged from clinical experience with such agents is the need for appropriate pharmacodiagnostic approaches to ensure the drugs are correctly targeted. Given the broad range of pharmacogenomic agents currently under evaluation for cancer therapy, it appears that a rapid extension of pharmacodiagnostic profiling will be required in the next 5-10 years, if not sooner. If this is to be successfully achieved, lessons learned in the past, particularly during the development of HER2 (ERBB2) testing for directing trastuzumab therapy in breast cancer, may provide a valuable framework for the development of future pharmacodiagnostic assays system. This article reviews the biological and clinical rationale for targeting breast cancer with trastuzumab and the steps taken to validate and improve pharmacodiagnostic procedures for testing tumor HER2 protein expression and HER2 gene amplification. Attention is given to quality assurance and reproducibility of testing approaches and the optimal selection of patients for response to trastuzumab. This approach serves as a paradigm for the future development of pharmacodiagnostic tests in oncology.
Bartlett
John M S
JM
Section of Surgical and Translational Research, Division of Cancer, Department of Surgery, Sciences and Molecular Pathology, Endocrine Cancer Group, Glasgow Royal Infirmary, University of Glasgow, Glasgow, Scotland. J.M.Bartlett@clinmed.gla.ac.uk
D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000032:analysis*; D001943:Breast Neoplasms / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D010597:Pharmacogenetics; D011237:Predictive Value of Tests; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis* / Q000235:genetics; D000068878:Trastuzumab
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab