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PUBLICATION: Performance of three biomarker immunohistochemistry for intrinsic breast cancer subtyping in the AMBER consortium.Cancer Epidemiol Biomarkers Prev. 2015 Dec 28. pii: cebp.0874.2015.

by Allott EH, Cohen SM, Geradts J, Sun X, Khoury T, Bshara W, Zirpoli GR, Miller CR, Hwang H, Thorne LB, O'Connor S, Tse CK, Bell MB, Hu Z, Li Y, Kirk EL, Bethea TN, Perou CM, Palmer JR, Ambrosone CB, Olshan AF, Troester MA.
Mon, Dec 28th 2015 04:00 pm

 ABSTRACT: BACKGROUND: Classification of breast cancer into intrinsic subtypes has clinical and epidemiologic importance. To examine accuracy of immunohistochemistry (IHC)-based methods for identifying intrinsic subtypes, a three-biomarker IHC panel was compared to 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 (TMAs) 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 to 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%), while 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 non-basal-like, while 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.

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