title: American Society of Clinical Oncology/College of American Pathologists guideline recommendations for human epidermal growth factor receptor 2 testing in breast cancer.
abstract: OBJECTIVE
  To develop a guideline to improve the accuracy of human epidermal growth factor receptor 2 (HER2) testing in invasive breast cancer and its utility as a predictive marker.
  
  
  METHODS
  The American Society of Clinical Oncology and the College of American Pathologists convened an expert panel, which conducted a systematic review of the literature and developed recommendations for optimal HER2 testing performance. The guideline was reviewed by selected experts and approved by the board of directors for both organizations.
  
  
  RESULTS
  Approximately 20% of current HER2 testing may be inaccurate. When carefully validated testing is performed, available data do not clearly demonstrate the superiority of either immunohistochemistry (IHC) or in situ hybridization (ISH) as a predictor of benefit from anti-HER2 therapy.
  
  
  CONCLUSIONS
  The panel recommends that HER2 status should be determined for all invasive breast cancer. A testing algorithm that relies on accurate, reproducible assay performance, including newly available types of brightfield ISH, is proposed. Elements to reliably reduce assay variation (for example, specimen handling, assay exclusion, and reporting criteria) are specified. An algorithm defining positive, equivocal, and negative values for both HER2 protein expression and gene amplification is recommended: a positive HER2 result is IHC staining of 3+ (uniform, intense membrane staining of > 30% of invasive tumor cells), a fluorescent in situ hybridization (FISH) result of more than six HER2 gene copies per nucleus or a FISH ratio (HER2 gene signals to chromosome 17 signals) of more than 2.2; a negative result is an IHC staining of 0 or 1+, a FISH result of less than 4.0 HER2 gene copies per nucleus, or FISH ratio of less than 1.8. Equivocal results require additional action for final determination. It is recommended that to perform HER2 testing, laboratories show 95% concordance with another validated test for positive and negative assay values. The panel strongly recommends validation of laboratory assay or modifications, use of standardized operating procedures, and compliance with new testing criteria to be monitored with the use of stringent laboratory accreditation standards, proficiency testing, and competency assessment. The panel recommends that HER2 testing be done in a CAP-accredited laboratory or in a laboratory that meets the accreditation and proficiency testing requirements set out by this document.
authors.affiliation: American Society of Clinical Oncology, Alexandria, VA, USA.
authors.forename: Antonio C
authors.initials: AC
authors.lastname: Wolff
authors.forename: M Elizabeth H
authors.initials: ME
authors.lastname: Hammond
authors.forename: Jared N
authors.initials: JN
authors.lastname: Schwartz
authors.forename: Karen L
authors.initials: KL
authors.lastname: Hagerty
authors.forename: D Craig
authors.initials: DC
authors.lastname: Allred
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Cote
authors.forename: Mitchell
authors.initials: M
authors.lastname: Dowsett
authors.forename: Patrick L
authors.initials: PL
authors.lastname: Fitzgibbons
authors.forename: Wedad M
authors.initials: WM
authors.lastname: Hanna
authors.forename: Amy
authors.initials: A
authors.lastname: Langer
authors.forename: Lisa M
authors.initials: LM
authors.lastname: McShane
authors.forename: Soonmyung
authors.initials: S
authors.lastname: Paik
authors.forename: Mark D
authors.initials: MD
authors.lastname: Pegram
authors.forename: Edith A
authors.initials: EA
authors.lastname: Perez
authors.forename: Michael F
authors.initials: MF
authors.lastname: Press
authors.forename: Anthony
authors.initials: A
authors.lastname: Rhodes
authors.forename: Catharine
authors.initials: C
authors.lastname: Sturgeon
authors.forename: Sheila E
authors.initials: SE
authors.lastname: Taube
authors.forename: Raymond
authors.initials: R
authors.lastname: Tubbs
authors.forename: Gail H
authors.initials: GH
authors.lastname: Vance
authors.forename: Marc
authors.initials: M
authors.lastname: van de Vijver
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Wheeler
authors.forename: Daniel F
authors.initials: DF
authors.lastname: Hayes
mesh_terms: D005260:Female; D006801:Humans; D000465:Algorithms; D014408:Biomarkers, Tumor; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism; D002986:Clinical Trials as Topic; D066246:ErbB Receptors / Q000096:biosynthesis / Q000235:genetics; D018734:Genes, erbB-2; D007150:Immunohistochemistry / Q000379:methods; D017403:In Situ Hybridization / Q000379:methods; D018719:Erb-b2 Receptor Tyrosine Kinases; D015203:Reproducibility of Results; D012196:Review Literature as Topic
chemical_list: D014408:Biomarkers, Tumor; D066246:ErbB Receptors; D018719:Erb-b2 Receptor Tyrosine Kinases; C508053:ERBB2 protein, human