title: Clinical and health economic outcomes of alternative HER2 test strategies for guiding adjuvant trastuzumab therapy.
abstract: OBJECTIVE
  To evaluate the clinical outcomes and cost-effectiveness of human epidermal growth factor receptor 2 (HER2) testing strategies to guide adjuvant trastuzumab (AT) therapy in women with HER2-positive breast cancer.
  
  
  METHODS
  A literature review produced 72 studies comparing HER2 test methods, and we computed concordance (assuming fluorescence in situ hybridization [FISH] as a reference assay) to assess performance relative to American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) guidelines. An economic analysis provided cost-effectiveness of alternative strategies, including a Monte Carlo simulation to vary key assumptions such as test price and performance.
  
  
  RESULTS
  Of 46 studies comparing immunohistochemistry (IHC) and FISH, only seven met the ASCO/CAP guideline of 95% or better concordance. A total of 14 out of 21 studies comparing chromogenic in situ hybridization and three out of five studies comparing silver-enhanced in situ hybridization met the guideline. Confirmation of IHC 2+ and 3+ and primary FISH strategies are likely to reduce costs and improve quality of life relative to confirmation of IHC 2+ only. Initial testing with a gene amplification-based assay is probably a cost-effective alternative to confirmation of IHC 2+ and 3+. The results are not sensitive to varying test price but are sensitive to test accuracy below 98%.
  
  
  CONCLUSIONS
  Using a primary gene amplification-based assay to guide AT therapy for HER2-positive breast cancer probably results in lower US medical costs, increased life-years and increased quality of life compared with confirmation of IHC 2+ with a gene amplification-based assay. We recommend the ASCO/CAP guidelines reflect 98% or greater concordance relative to a reference assay. Additional research regarding therapy response is required to further differentiate between gene amplification-based assays.
authors.affiliation: Altarum Institute, 3520 Green Court, Suite 300, Ann Arbor, MI 48105, USA. jim.lee@altarum.org
authors.forename: James A
authors.initials: JA
authors.lastname: Lee
authors.forename: Megan
authors.initials: M
authors.lastname: Shaheen
authors.forename: Thomas
authors.initials: T
authors.lastname: Walke
authors.forename: Matt
authors.initials: M
authors.lastname: Daly
mesh_terms: D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000191:economics / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000191:economics / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000191:economics; D017024:Chemotherapy, Adjuvant / Q000191:economics / Q000379:methods; D003362:Cost-Benefit Analysis; D005260:Female; D005784:Gene Amplification; D006801:Humans; D007150:Immunohistochemistry / Q000191:economics / Q000379:methods; D017404:In Situ Hybridization, Fluorescence / Q000191:economics / Q000379:methods; D017410:Practice Guidelines as Topic; D011788:Quality of Life; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D000068878:Trastuzumab
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab