{"entity":{"id":"paper-burstein-tnbc-genomic-subtypes-ccr-2015","kind":"paper","name":"Comprehensive genomic analysis identifies novel subtypes and targets of triple-negative breast cancer","aka":[],"tldr":"A 2015 Baylor study of 198 triple-negative tumours that found four stable subtypes, luminal androgen receptor, mesenchymal, basal-like immune-suppressed and basal-like immune-activated, with the immune-activated group faring best and the immune-suppressed worst.","summary":"Burstein, Tsimelzon, Poage, Covington and colleagues profiled RNA and DNA in 198 triple-negative tumours (oestrogen receptor negativity defined as Allred score 2 or less, more than 50 percent cellularity; discovery 84, validation 114) collected at Baylor College of Medicine, with an external set of seven public studies for confirmation. Four subtypes were identified and confirmed: luminal androgen receptor (LAR), mesenchymal (MES), basal-like immunosuppressed (BLIS) and basal-like immune-activated (BLIA). Prognosis was worst for BLIS and best for BLIA for both disease-free survival (p=0.042 and 0.041) and disease-specific survival (p=0.039 and 0.029). Copy number analysis separated LAR from the other three and suggested amplification drives expression in some cases (FGFR2 in BLIS). Candidate subtype-specific targets were androgen receptor and MUC1 (LAR), PDGF receptor A and c-Kit (MES), VTCN1 (BLIS) and Stat molecules and cytokines (BLIA).","asOf":"2026-09-24","links":[{"label":"Clin Cancer Res 2015","url":"https://doi.org/10.1158/1078-0432.CCR-14-0432"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/25208879/"}],"tags":["tnbc-evidence"],"related":["paper-lehmann-tnbc-subtypes-jci-2011"],"cancers":["tnbc"],"sections":[],"technologies":["rna-seq"],"targets":["androgen-receptor","b7h4","fgfr2","pdgfrb"],"drugs":[],"companies":[],"institutions":["baylor-duncan"],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-tumor-heterogeneity","b-immunotherapy-response"],"keyPapers":[],"journals":["clinical-cancer-research"],"dependsOn":[],"notes":[],"journal":"Clinical Cancer Research","year":2015,"doi":"10.1158/1078-0432.CCR-14-0432","pmid":"25208879","authors":"Burstein MD, Tsimelzon A, Poage GM, et al.","paperType":"translational","findings":["Four subtypes confirmed in 198 tumours and seven external studies: LAR, MES, BLIS, BLIA.","Disease-free survival worst for BLIS (p=0.042) and best for BLIA (p=0.041); disease-specific survival likewise (p=0.039 and 0.029).","Candidate targets: androgen receptor and MUC1; PDGFRA and c-Kit; VTCN1; Stat signalling."],"whatItMeans":"Independently arrived at the same partition as the refined Lehmann scheme and added the insight that immune activation within basal-like tumours separates good from poor prognosis, the biology immunotherapy would exploit three years later.","caveats":["Single-institution discovery set.","Candidate targets are computational; VTCN1 (B7-H4) antibody-drug conjugates are only now in early trials."],"changedPractice":false,"participants":198},"route":"/key-papers/paper-burstein-tnbc-genomic-subtypes-ccr-2015/","neighbours":{"paper":[{"id":"paper-lehmann-tnbc-subtypes-jci-2011","kind":"paper","name":"Identification of human triple-negative breast cancer subtypes and preclinical models for selection of targeted therapies","route":"/key-papers/paper-lehmann-tnbc-subtypes-jci-2011/"}],"cancer":[{"id":"tnbc","kind":"cancer","name":"Triple-negative breast cancer (TNBC)","route":"/cancers/tnbc/"}],"technology":[{"id":"rna-seq","kind":"technology","name":"RNA sequencing & expression profiling","route":"/technologies/rna-seq/"}],"target":[{"id":"androgen-receptor","kind":"target","name":"Androgen receptor","route":"/targets/androgen-receptor/"},{"id":"b7h4","kind":"target","name":"B7-H4 (VTCN1)","route":"/targets/b7h4/"},{"id":"fgfr2","kind":"target","name":"FGFR2","route":"/targets/fgfr2/"},{"id":"pdgfrb","kind":"target","name":"PDGFRB","route":"/targets/pdgfrb/"}],"institution":[{"id":"baylor-duncan","kind":"institution","name":"Dan L Duncan Comprehensive Cancer Center, Baylor College of Medicine","route":"/institutions/baylor-duncan/"}],"bottleneck":[{"id":"b-immunotherapy-response","kind":"bottleneck","name":"No one can predict who responds to immunotherapy","route":"/bottlenecks/b-immunotherapy-response/"},{"id":"b-tumor-heterogeneity","kind":"bottleneck","name":"Tumour heterogeneity and clonal evolution","route":"/bottlenecks/b-tumor-heterogeneity/"}],"journal":[{"id":"clinical-cancer-research","kind":"journal","name":"Clinical Cancer Research","route":"/journals/clinical-cancer-research/"}],"roadmap":[{"id":"tnbc-roadmap","kind":"roadmap","name":"Triple-negative breast cancer roadmap: from a remainder defined by three negative tests to immunotherapy, antibody-drug conjugates and the residual disease problem","route":"/roadmaps/tnbc-roadmap/"}]}}