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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.
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.
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.
The first evidence that molecular subtype predicts chemotherapy response in triple-negative disease, and the origin of the observation that the immune signal in these tumours is real and measurable, which tumour-infiltrating lymphocyte scoring later turned into a prognostic tool.
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.
Shares Tumour heterogeneity and clonal evolution, PI3K / AKT / mTOR, Triple-negative breast cancer roadmap: from a remainder defined by three negative tests to immunotherapy, antibody-drug conjugates and the residual disease problem, Triple-negative breast cancer (TNBC) and the tag tnbc-evidence.
Shares RNA sequencing & expression profiling, Triple-negative breast cancer roadmap: from a remainder defined by three negative tests to immunotherapy, antibody-drug conjugates and the residual disease problem, Triple-negative breast cancer (TNBC) and the tag tnbc-evidence.
Shares Triple-negative breast cancer roadmap: from a remainder defined by three negative tests to immunotherapy, antibody-drug conjugates and the residual disease problem, Platinum agents, Triple-negative breast cancer (TNBC) and the tag tnbc-evidence.
Shares Triple-negative breast cancer roadmap: from a remainder defined by three negative tests to immunotherapy, antibody-drug conjugates and the residual disease problem, Platinum agents, Triple-negative breast cancer (TNBC) and the tag tnbc-evidence.
Shares Triple-negative breast cancer roadmap: from a remainder defined by three negative tests to immunotherapy, antibody-drug conjugates and the residual disease problem, Platinum agents, Triple-negative breast cancer (TNBC) and the tag tnbc-evidence.
Shares Triple-negative breast cancer roadmap: from a remainder defined by three negative tests to immunotherapy, antibody-drug conjugates and the residual disease problem, Triple-negative breast cancer (TNBC) and the tag tnbc-evidence.
Shares Triple-negative breast cancer roadmap: from a remainder defined by three negative tests to immunotherapy, antibody-drug conjugates and the residual disease problem, Platinum agents, Triple-negative breast cancer (TNBC) and the tag tnbc-evidence.
Shares Triple-negative breast cancer roadmap: from a remainder defined by three negative tests to immunotherapy, antibody-drug conjugates and the residual disease problem, Triple-negative breast cancer (TNBC) and the tag tnbc-evidence.