title: Reflex Repeat HER2 Testing of Grade 3 Breast Carcinoma at Excision Using Immunohistochemistry and In Situ Analysis: Frequency of HER2 Discordance and Utility of Core Needle Biopsy Parameters to Refine Case Selection.
abstract: OBJECTIVE
  The updated American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) guidelines (2013) for human epidermal growth factor receptor 2 (HER2) testing in breast cancer recommend repeat testing at excision of HER2-negative grade 3 breast tumors. This study aimed to identify the rate of HER2 discordance in this cohort of cases.
  
  
  METHODS
  All HER2-negative grade 3 tumors diagnosed at a single institution over a 15-month period had reflex repeat HER2 testing at excision : HER2 testing was performed in accordance with ASCO/CAP guidelines using immunohistochemistry (IHC) and dual in situ hybridization (ISH).
  
  
  RESULTS
  One hundred cases were identified over the study period. HER2 was amplified at excision in three cases. The discordant tumors showed equivocal IHC at excision with low-level amplification on dual ISH. All discordant cases showed equivocal IHC on core needle biopsy (CNB) specimens and/or tumor upgrade at excision.
  
  
  CONCLUSIONS
  Our series demonstrated a high concordance rate (97%) for HER2 at excision in grade 3 breast tumors with a negative core biopsy result. These findings suggest that reflex repeat HER2 testing of all these cases, which has significant cost and workload implications, may not be justified. Features that may indicate HER2 heterogeneity, such as equivocal IHC on CNB specimens or tumor upgrade at excision, may help refine selection of cases for repeat testing.
authors.affiliation: From the Department of Histopathology, Cork University Hospital, Cork, Ireland.
authors.forename: Susan
authors.initials: S
authors.lastname: Prendeville
authors.affiliation: From the Department of Histopathology, Cork University Hospital, Cork, Ireland.
authors.forename: Linda
authors.initials: L
authors.lastname: Feeley
authors.affiliation: From the Department of Histopathology, Cork University Hospital, Cork, Ireland.
authors.forename: Michael W
authors.initials: MW
authors.lastname: Bennett
authors.affiliation: From the Department of Histopathology, Cork University Hospital, Cork, Ireland.
authors.forename: Fionnuala
authors.initials: F
authors.lastname: O'Connell
authors.affiliation: From the Department of Histopathology, Cork University Hospital, Cork, Ireland. tarajane.browne@hse.ie.
authors.forename: Tara Jane
authors.initials: TJ
authors.lastname: Browne
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D062005:Biopsy, Large-Core Needle; D001940:Breast / Q000378:metabolism / Q000473:pathology*; D001943:Breast Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008875:Middle Aged; D060787:Neoplasm Grading; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*
chemical_list: D018719:Erb-b2 Receptor Tyrosine Kinases; C508053:ERBB2 protein, human
keywords: Breast carcinoma; Core biopsy; HER2