{"entity":{"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","aka":[],"tldr":"The 2011 Vanderbilt analysis of 587 triple-negative tumours that split the disease into six molecular groups, two basal-like, an immune group, two mesenchymal groups and a luminal androgen receptor group, and matched each to cell lines and candidate drugs.","summary":"Lehmann, Bauer, Chen, Sanders and colleagues analysed gene expression from 21 breast cancer data sets, identified 587 triple-negative cases and by cluster analysis defined six subtypes with distinct expression and ontologies: basal-like 1 and 2 (BL1, BL2), immunomodulatory (IM), mesenchymal (M), mesenchymal stem-like (MSL) and luminal androgen receptor (LAR). Cell line models representing each subtype were identified and their predicted driver pathways targeted pharmacologically. BL1 and BL2 had higher expression of cell cycle and DNA damage response genes and their cell lines responded preferentially to cisplatin; M and MSL were enriched for epithelial-mesenchymal transition and growth factor pathways and responded to a PI3K/mTOR inhibitor (NVP-BEZ235) and dasatinib; LAR, associated with decreased relapse-free survival, was driven by androgen receptor signalling and its cell lines were uniquely sensitive to bicalutamide.","asOf":"2026-09-24","links":[{"label":"J Clin Invest 2011","url":"https://doi.org/10.1172/JCI45014"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/21633166/"}],"tags":["tnbc-evidence"],"related":["paper-lehmann-tnbctype-4-refinement-plos-one-2016","paper-burstein-tnbc-genomic-subtypes-ccr-2015"],"cancers":["tnbc"],"sections":[],"technologies":["rna-seq","platinum"],"targets":["androgen-receptor","egfr"],"drugs":[],"companies":[],"institutions":["vanderbilt-ingram"],"pathways":["ddr","emt","pi3k-akt-mtor","ar-signaling"],"terms":[],"trials":[],"people":[],"bottlenecks":["b-tumor-heterogeneity"],"keyPapers":[],"journals":["jci"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Investigation","year":2011,"doi":"10.1172/JCI45014","pmid":"21633166","authors":"Lehmann BD, Bauer JA, Chen X, et al.","paperType":"translational","findings":["Six subtypes from 587 triple-negative cases across 21 data sets: BL1, BL2, IM, M, MSL, LAR.","BL1 and BL2 cell lines preferentially sensitive to cisplatin; M and MSL to PI3K/mTOR and abl/src inhibition; LAR to bicalutamide."],"whatItMeans":"The vocabulary used on the triple-negative page (basal-like 1 and 2, mesenchymal, luminal androgen receptor, immunomodulatory) comes from this paper; it made triple-negative breast cancer several diseases with several possible drugs rather than one disease with none.","caveats":["Subtypes derived from bulk expression; the 2016 refinement showed two of the six came from infiltrating immune and stromal cells.","Drug sensitivities are cell line results; no subtype-directed therapy has yet succeeded in a phase 3 trial."],"changedPractice":true,"participants":587},"route":"/key-papers/paper-lehmann-tnbc-subtypes-jci-2011/","neighbours":{"paper":[{"id":"paper-burstein-tnbc-genomic-subtypes-ccr-2015","kind":"paper","name":"Comprehensive genomic analysis identifies novel subtypes and targets of triple-negative breast cancer","route":"/key-papers/paper-burstein-tnbc-genomic-subtypes-ccr-2015/"},{"id":"paper-lehmann-tnbctype-4-refinement-plos-one-2016","kind":"paper","name":"Refinement of Triple-Negative Breast Cancer Molecular Subtypes: Implications for Neoadjuvant Chemotherapy Selection","route":"/key-papers/paper-lehmann-tnbctype-4-refinement-plos-one-2016/"}],"cancer":[{"id":"tnbc","kind":"cancer","name":"Triple-negative breast cancer (TNBC)","route":"/cancers/tnbc/"}],"technology":[{"id":"platinum","kind":"technology","name":"Platinum agents","route":"/technologies/platinum/"},{"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":"egfr","kind":"target","name":"EGFR","route":"/targets/egfr/"}],"institution":[{"id":"vanderbilt-ingram","kind":"institution","name":"Vanderbilt-Ingram Cancer Center","route":"/institutions/vanderbilt-ingram/"}],"pathway":[{"id":"ar-signaling","kind":"pathway","name":"Androgen receptor signalling","route":"/pathways/ar-signaling/"},{"id":"ddr","kind":"pathway","name":"DNA damage response & homologous recombination","route":"/pathways/ddr/"},{"id":"emt","kind":"pathway","name":"Epithelial-mesenchymal transition & drug efflux","route":"/pathways/emt/"},{"id":"pi3k-akt-mtor","kind":"pathway","name":"PI3K / AKT / mTOR","route":"/pathways/pi3k-akt-mtor/"}],"bottleneck":[{"id":"b-tumor-heterogeneity","kind":"bottleneck","name":"Tumour heterogeneity and clonal evolution","route":"/bottlenecks/b-tumor-heterogeneity/"}],"journal":[{"id":"jci","kind":"journal","name":"Journal of Clinical Investigation","route":"/journals/jci/"}],"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/"}]}}