Citation
Allott, Emma H.; Cohen, Stephanie M.; Geradts, Joseph; Sun, Xuezheng; Khoury, Thaer; Bshara, Wiam; Zirpoli, Gary R.; Miller, C. Ryan; Hwang, Helena; & Thorne, Leigh B., et al. (2016). Performance of Three-Biomarker Immunohistochemistry for Intrinsic Breast Cancer Subtyping in the AMBER Consortium. Cancer Epidemiology, Biomarkers & Prevention, 25(3), 470-478. PMCID: PMC4779705Abstract
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.
URL
http://dx.doi.org/10.1158/1055-9965.epi-15-0874Reference Type
Journal ArticleYear Published
2016Journal Title
Cancer Epidemiology, Biomarkers & PreventionAuthor(s)
Allott, Emma H.Cohen, Stephanie M.
Geradts, Joseph
Sun, Xuezheng
Khoury, Thaer
Bshara, Wiam
Zirpoli, Gary R.
Miller, C. Ryan
Hwang, Helena
Thorne, Leigh B.
O'Connor, Siobhan
Tse, Chiu-Kit J.
Bell, Mary Elizabeth
Hu, Zhiyuan
Li, Yan
Kirk, Erin L.
Bethea, Traci N.
Perou, Charles M.
Palmer, Julie R.
Ambrosone, Christine B.
Olshan, Andrew F.
Troester, Melissa A.