title: Performance of Three-Biomarker Immunohistochemistry for Intrinsic Breast Cancer Subtyping in the AMBER Consortium.
abstract: BACKGROUND
  Classification of breast cancer into intrinsic subtypes has clinical and epidemiologic importance. To examine accuracy of IHC-based methods for identifying intrinsic subtypes, a three-biomarker IHC panel was compared with the clinical record and RNA-based intrinsic (PAM50) subtypes.
  
  
  METHODS
  Automated scoring of estrogen receptor (ER), progesterone receptor (PR), and HER2 was performed on IHC-stained tissue microarrays comprising 1,920 cases from the African American Breast Cancer Epidemiology and Risk (AMBER) consortium. Multiple cores (1-6/case) were collapsed to classify cases, and automated scoring was compared with the clinical record and to RNA-based subtyping.
  
  
  RESULTS
  Automated analysis of the three-biomarker IHC panel produced high agreement with the clinical record (93% for ER and HER2, and 88% for PR). Cases with low tumor cellularity and smaller core size had reduced agreement with the clinical record. IHC-based definitions had high agreement with the clinical record regardless of hormone receptor positivity threshold (1% vs. 10%), but a 10% threshold produced highest agreement with RNA-based intrinsic subtypes. Using a 10% threshold, IHC-based definitions identified the basal-like intrinsic subtype with high sensitivity (86%), although sensitivity was lower for luminal A, luminal B, and HER2-enriched subtypes (76%, 40%, and 37%, respectively).
  
  
  CONCLUSIONS
  Three-biomarker IHC-based subtyping has reasonable accuracy for distinguishing basal-like from nonbasal-like, although additional biomarkers are required for accurate classification of luminal A, luminal B, and HER2-enriched cancers.
  
  
  CONCLUSIONS
  Epidemiologic studies relying on three-biomarker IHC status for subtype classification should use caution when distinguishing luminal A from luminal B and when interpreting findings for HER2-enriched cancers.
authors.affiliation: Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina. Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
authors.forename: Emma H
authors.initials: EH
authors.lastname: Allott
authors.affiliation: Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina. Translational Pathology Laboratory, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
authors.forename: Stephanie M
authors.initials: SM
authors.lastname: Cohen
authors.affiliation: Department of Pathology, Duke University, Durham, North Carolina.
authors.forename: Joseph
authors.initials: J
authors.lastname: Geradts
authors.affiliation: Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
authors.forename: Xuezheng
authors.initials: X
authors.lastname: Sun
authors.affiliation: Department of Pathology, Roswell Park Cancer Institute, Buffalo, New York.
authors.forename: Thaer
authors.initials: T
authors.lastname: Khoury
authors.affiliation: Department of Pathology, Roswell Park Cancer Institute, Buffalo, New York.
authors.forename: Wiam
authors.initials: W
authors.lastname: Bshara
authors.affiliation: Cancer Prevention and Control, Roswell Park Cancer Institute, Buffalo, New York.
authors.forename: Gary R
authors.initials: GR
authors.lastname: Zirpoli
authors.affiliation: Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina. Translational Pathology Laboratory, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina. Department of Pathology and Laboratory Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
authors.forename: C Ryan
authors.initials: CR
authors.lastname: Miller
authors.affiliation: Department of Pathology, University of Texas Southwestern, Dallas, Texas.
authors.forename: Helena
authors.initials: H
authors.lastname: Hwang
authors.affiliation: Department of Pathology and Laboratory Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
authors.forename: Leigh B
authors.initials: LB
authors.lastname: Thorne
authors.affiliation: Department of Pathology and Laboratory Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
authors.forename: Siobhan
authors.initials: S
authors.lastname: O'Connor
authors.affiliation: Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
authors.forename: Chiu-Kit
authors.initials: CK
authors.lastname: Tse
authors.affiliation: Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
authors.forename: Mary B
authors.initials: MB
authors.lastname: Bell
authors.affiliation: Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
authors.forename: Zhiyuan
authors.initials: Z
authors.lastname: Hu
authors.affiliation: Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
authors.forename: Erin L
authors.initials: EL
authors.lastname: Kirk
authors.affiliation: Slone Epidemiology Center, Boston University, Boston, Massachusetts.
authors.forename: Traci N
authors.initials: TN
authors.lastname: Bethea
authors.affiliation: Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
authors.forename: Charles M
authors.initials: CM
authors.lastname: Perou
authors.affiliation: Slone Epidemiology Center, Boston University, Boston, Massachusetts.
authors.forename: Julie R
authors.initials: JR
authors.lastname: Palmer
authors.affiliation: Cancer Prevention and Control, Roswell Park Cancer Institute, Buffalo, New York.
authors.forename: Christine B
authors.initials: CB
authors.lastname: Ambrosone
authors.affiliation: Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina. Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
authors.forename: Andrew F
authors.initials: AF
authors.lastname: Olshan
authors.affiliation: Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina. Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina. troester@unc.edu.
authors.forename: Melissa A
authors.initials: MA
authors.lastname: Troester
mesh_terms: D001943:Breast Neoplasms / Q000276:immunology* / Q000473:pathology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D046888:Tissue Array Analysis