title: HER2 testing in a population-based study of patients with metastatic breast cancer treated with trastuzumab.
abstract: BACKGROUND
  The development of trastuzumab has led to new therapeutic strategies for patients with breast cancer. Trastuzumab has been shown to only be effective in those patients whose cancers are HER2 positive by either immunohistochemistry (IHC) or fluorescence in situ hybridization (FISH).
  
  
  OBJECTIVE
  To determine the accuracy of HER2 testing in 2 provinces in Canada.
  
  
  METHODS
  Patients with metastatic breast cancer diagnosed between 1999 and 2002 who were HER2 positive in the local laboratories were included in this study. All cases were retested centrally, by IHC (using 4 methods) and FISH. In addition, 205 locally reported HER2-negative metastatic breast cancer cases were retested centrally.
  
  
  RESULTS
  Concordance between the 505 local IHC-positive cases with central IHC testing varied between 79.3% and 89.6% depending on the IHC method and scoring method used. HER2 gene amplification by FISH was present in 86.1% of local IHC-positive cases. Concordance between the 205 local IHC-negative tumors with central testing ranged between 94.8% and 100% for IHC and was 98.5% for FISH.
  
  
  CONCLUSIONS
  This study demonstrated that locally reported HER2-negative results were highly accurate, but less accuracy was demonstrated with local HER2-positive results. These results emphasize the need for participation in a quality assurance program.
authors.affiliation: Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, 600 University Ave, Toronto, Ontario, Canada M5G 1X5. fomalley@mtsinai.on.ca
authors.forename: Frances P
authors.initials: FP
authors.lastname: O'Malley
authors.forename: Tom
authors.initials: T
authors.lastname: Thomson
authors.forename: Jim
authors.initials: J
authors.lastname: Julian
authors.forename: Cherry
authors.initials: C
authors.lastname: Have
authors.forename: Roxanne
authors.initials: R
authors.lastname: Cosby
authors.forename: Roxanne
authors.initials: R
authors.lastname: Crosby
authors.forename: Karen
authors.initials: K
authors.lastname: Gelmon
authors.forename: Irene
authors.initials: I
authors.lastname: Andrulis
authors.forename: Tim
authors.initials: T
authors.lastname: Whelan
mesh_terms: D000230:Adenocarcinoma / Q000175:diagnosis* / Q000188:drug therapy / Q000235:genetics / Q000556:secondary; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000032:analysis / Q000235:genetics*; D001943:Breast Neoplasms / Q000175:diagnosis* / Q000188:drug therapy / Q000235:genetics; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D011237:Predictive Value of Tests; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis / Q000235:genetics*; D015203:Reproducibility of Results; D000068878:Trastuzumab
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab