Performance of Three-Biomarker Immunohistochemistry for Intrinsic Breast Cancer Subtyping in the AMBER Consortium

Emma H Allott, Stephanie M Cohen, Joseph Geradts, Xuezheng Sun, Thaer Khoury, Wiam Bshara, Gary R Zirpoli, C Ryan Miller, Helena Hwang, Leigh B Thorne, Siobhan O'Connor, Chiu-Kit Tse, Mary B Bell, Zhiyuan Hu, Yan Li, Erin L Kirk, Traci N Bethea, Charles M Perou, Julie R Palmer, Christine B AmbrosoneAndrew F Olshan, Melissa A Troester

Research output: Contribution to journalArticlepeer-review

35 Citations (Scopus)

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).

CONCLUSION: 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.

IMPACT: 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.

Original languageEnglish
Pages (from-to)470-478
Number of pages9
JournalCancer Epidemiology Biomarkers & Prevention
Volume25
Issue number3
Early online date28 Dec 2015
DOIs
Publication statusPublished - Mar 2016
Externally publishedYes

Keywords

  • Breast Neoplasms/immunology
  • Female
  • Humans
  • Immunohistochemistry
  • Tissue Array Analysis

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