{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Allott EH"],"funding":["NIEHS NIH HHS","NCI NIH HHS"],"pagination":["470-8"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC4779705"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["25(3)"],"pubmed_abstract":["<h4>Background</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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).<h4>Conclusion</h4>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.<h4>Impact</h4>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."],"journal":["Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology"],"pubmed_title":["Performance of Three-Biomarker Immunohistochemistry for Intrinsic Breast Cancer Subtyping in the AMBER Consortium."],"pmcid":["PMC4779705"],"funding_grant_id":["P50 CA058223","P30 CA016086","P01 CA151135","UM1 CA164974","P30 ES010126","P50-CA058223","3P30CA016086","U01-CA179715","U01 CA179715","5P01CA151135-04"],"pubmed_authors":["Zirpoli GR","Hu Z","Bethea TN","Miller CR","Kirk EL","Hwang H","Cohen SM","O'Connor S","Bell MB","Perou CM","Sun X","Olshan AF","Khoury T","Bshara W","Thorne LB","Palmer JR","Li Y","Allott EH","Geradts J","Troester MA","Tse CK","Ambrosone CB"],"additional_accession":[]},"is_claimable":false,"name":"Performance of Three-Biomarker Immunohistochemistry for Intrinsic Breast Cancer Subtyping in the AMBER Consortium.","description":"<h4>Background</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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).<h4>Conclusion</h4>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.<h4>Impact</h4>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.","dates":{"release":"2016-01-01T00:00:00Z","publication":"2016 Mar","modification":"2024-11-20T00:16:48.076Z","creation":"2019-03-27T02:10:33Z"},"accession":"S-EPMC4779705","cross_references":{"pubmed":["26711328"],"doi":["10.1158/1055-9965.EPI-15-0874","10.1158/1055-9965.epi-15-0874"]}}