title: Concordance between central and local laboratory HER2 testing from a community-based clinical study.
abstract: BACKGROUND
  Women with HER2-overexpressing breast cancer have an unfavorable prognosis. Trastuzumab improves survival when combined with chemotherapy in the first-line treatment of patients with HER2-overexpressing metastatic breast cancer and decreases the rate of disease relapse by 52% and the rate of death by 33% in women with HER2-overexpressing early-stage breast cancer. HER2 testing can be performed using immunohistochemistry (IHC) or fluorescence in situ hybridization (FISH) and can be performed at local pathology laboratories or at central/reference laboratories. Because of the significant benefit seen with trastuzumab, it is critical to accurately identify women most likely to benefit. The method and the location of HER2 testing contribute to the accuracy of test results.
  
  
  METHODS
  HER-First, a prospective, community-based, phase IV study of first-line trastuzumab/taxane therapy, enrolled patients with HER2-overexpressing metastatic breast cancer. Retesting of all tumor specimens by HER2 IHC and FISH at a high-volume, experienced laboratory was required.
  
  
  RESULTS
  Concordance between local and central laboratory HER2 IHC testing was highest for local IHC 3+ samples (n = 377; 77%) and lowest for IHC 2+ samples (n = 184; 26%). Thirty-three percent of samples testing IHC 2+ at a local laboratory tested FISH-positive at the central laboratory. Concordance between HER2 IHC and FISH results was higher when both tests were performed at the central laboratory.
  
  
  CONCLUSIONS
  Accurate HER2 test results are critical to identify patients who are appropriate candidates for trastuzumab, a therapy with significant clinical benefits in HER2-overexpressing breast cancer. These data show that HER2 testing is most accurate when performed at a high-volume reference laboratory.
authors.affiliation: Genentech, Inc, South San Francisco, CA 94080, USA. josina@gene.com
authors.forename: Josina C
authors.initials: JC
authors.lastname: Reddy
authors.forename: James D
authors.initials: JD
authors.lastname: Reimann
authors.forename: Steven M
authors.initials: SM
authors.lastname: Anderson
authors.forename: Pamela M
authors.initials: PM
authors.lastname: Klein
mesh_terms: D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000175:diagnosis* / Q000378:metabolism* / Q000473:pathology; D002986:Clinical Trials as Topic; D003153:Community Health Services; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D007753:Laboratories; D009362:Neoplasm Metastasis; D018579:Patient Selection; D011237:Predictive Value of Tests; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D015203:Reproducibility of Results; D000068878:Trastuzumab
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab