title: Human epidermal growth factor receptor 2 testing in invasive breast cancer: should histological grade, type and oestrogen receptor status influence the decision to repeat testing?
abstract: OBJECTIVE
  The recent American Society of Clinical Oncology/College of American Pathologists guidelines for human epidermal growth factor receptor 2 (HER2) testing in breast cancer recommend repeat testing based on tumour grade, tumour type, and hormone receptor status. The aim of this study was to test the value of these criteria.
  
  
  RESULTS
  HER2 status was concordant in the core biopsies and excision specimens in 392 of 400 invasive carcinomas. The major reasons for discordance were amplification around the cut-off for positivity and tumour heterogeneity. Of 116 grade 3 carcinomas that were HER2-negative in the core biopsy, four were HER2-positive in the excision specimen. Three of these four either showed borderline negative amplification in the core biopsy or were heterogeneous. None of the 55 grade 1 carcinomas were HER2-positive. Review of repeat testing of HER2 in routine practice suggested that it may also be of value for multifocal tumours and if recommended by the person assessing the in-situ hybridization.
  
  
  CONCLUSIONS
  Mandatory repeat HER2 testing of grade 3 HER2-negative carcinomas is not appropriate. This is particularly true if repeat testing is performed after borderline negative amplification in the core biopsy or in HER2-negative heterogeneous carcinomas.
authors.affiliation: Department of Histopathology, Nottingham City Hospital, Nottingham University Hospitals NHS Trust and the University of Nottingham, Nottingham, UK.
authors.forename: Emad A
authors.initials: EA
authors.lastname: Rakha
authors.affiliation: Department of Histopathology, Nottingham City Hospital, Nottingham University Hospitals NHS Trust and the University of Nottingham, Nottingham, UK.
authors.forename: Marian
authors.initials: M
authors.lastname: Pigera
authors.affiliation: Weill Cornell Breast Pathology Consultation Service Department of Pathology and Laboratory Medicine, New York Presbyterian Hospital, New York, NY, USA.
authors.forename: Sandra J
authors.initials: SJ
authors.lastname: Shin
authors.affiliation: Weill Cornell Breast Pathology Consultation Service Department of Pathology and Laboratory Medicine, New York Presbyterian Hospital, New York, NY, USA.
authors.forename: Timothy
authors.initials: T
authors.lastname: D'Alfonso
authors.affiliation: Department of Histopathology, Nottingham City Hospital, Nottingham University Hospitals NHS Trust and the University of Nottingham, Nottingham, UK.
authors.forename: Ian O
authors.initials: IO
authors.lastname: Ellis
authors.affiliation: Department of Histopathology, Nottingham City Hospital, Nottingham University Hospitals NHS Trust and the University of Nottingham, Nottingham, UK.
authors.forename: Andrew H S
authors.initials: AH
authors.lastname: Lee
mesh_terms: D014408:Biomarkers, Tumor / Q000378:metabolism*; D062005:Biopsy, Large-Core Needle; D001940:Breast / Q000473:pathology*; D001943:Breast Neoplasms / Q000175:diagnosis* / Q000378:metabolism; D018270:Carcinoma, Ductal, Breast / Q000175:diagnosis* / Q000378:metabolism; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D008495:Medical Oncology; D060787:Neoplasm Grading; D017410:Practice Guidelines as Topic; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D011960:Receptors, Estrogen / Q000378:metabolism; D014481:United States
chemical_list: D014408:Biomarkers, Tumor; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; C508053:ERBB2 protein, human
keywords: HER2 status; carcinoma of breast; core biopsy; excision specimen