title: Genetic heterogeneity in HER2 testing in breast cancer: panel summary and guidelines.
abstract: BACKGROUND
  Intratumoral heterogeneity of HER2 gene amplification has been well documented and represents subclonal diversity within the tumor. The reported incidence of intratumor HER2 amplification genetic heterogeneity ranges in the literature from approximately 5% to 30%. The presence of HER2 genetic heterogeneity may increase subjectivity in HER2 interpretation by the pathologist.
  
  
  OBJECTIVE
  To define HER2 genetic heterogeneity and to provide practice guidelines for examining and reporting breast tumors with genetic heterogeneity for improvement of HER2 testing in breast cancer.
  
  
  METHODS
  We convened an expert panel to discuss HER2 gene amplification testing by fluorescence in situ hybridization. Components addressed included a definition of HER2 amplification heterogeneity, practice guidelines for examination of the tissue, and reporting criteria for this analysis.
  
  
  RESULTS
  Genetic heterogeneity for amplification of HER2 gene status in invasive breast cancer is defined and guidelines established for assessing and reporting HER2 results in these cases. These guidelines are additive to and expand those published in 2007 by the American Society of Clinical Oncology and the College of American Pathologists.
  
  
  CONCLUSIONS
  Standardized methods for analysis will improve the accuracy and consistency of interpretation of HER2 gene amplification status in breast cancer.
authors.affiliation: Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN 46202, USA. ghvance@iupui.edu
authors.forename: Gail H
authors.initials: GH
authors.lastname: Vance
authors.forename: Todd S
authors.initials: TS
authors.lastname: Barry
authors.forename: Kenneth J
authors.initials: KJ
authors.lastname: Bloom
authors.forename: Patrick L
authors.initials: PL
authors.lastname: Fitzgibbons
authors.forename: David G
authors.initials: DG
authors.lastname: Hicks
authors.forename: Robert B
authors.initials: RB
authors.lastname: Jenkins
authors.forename: Diane L
authors.initials: DL
authors.lastname: Persons
authors.forename: Raymond R
authors.initials: RR
authors.lastname: Tubbs
authors.forename: M Elizabeth H
authors.initials: ME
authors.lastname: Hammond
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics*; D005260:Female; D005784:Gene Amplification; D018734:Genes, erbB-2; D018740:Genetic Heterogeneity; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D021141:Nucleic Acid Amplification Techniques