Genomic and Transcriptomic Landscape of Triple-Negative Breast Cancers: Subtypes and Treatment Strategies

Cancer Cell. 2019 Mar 18;35(3):428-440.e5. doi: 10.1016/j.ccell.2019.02.001. Epub 2019 Mar 7.

Abstract

We comprehensively analyzed clinical, genomic, and transcriptomic data of a cohort of 465 primary triple-negative breast cancer (TNBC). PIK3CA mutations and copy-number gains of chromosome 22q11 were more frequent in our Chinese cohort than in The Cancer Genome Atlas. We classified TNBCs into four transcriptome-based subtypes: (1) luminal androgen receptor (LAR), (2) immunomodulatory, (3) basal-like immune-suppressed, and (4) mesenchymal-like. Putative therapeutic targets or biomarkers were identified among each subtype. Importantly, the LAR subtype showed more ERBB2 somatic mutations, infrequent mutational signature 3 and frequent CDKN2A loss. The comprehensive profile of TNBCs provided here will serve as a reference to further advance the understanding and precision treatment of TNBC.

Keywords: genomic; molecular subtype; precision therapies; target; transcriptomic; triple-negative breast cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Asian Continental Ancestry Group / genetics
  • Biomarkers, Tumor / genetics
  • Chromosomes, Human, Pair 22 / genetics
  • Class I Phosphatidylinositol 3-Kinases / genetics*
  • Cyclin-Dependent Kinase Inhibitor p16 / genetics*
  • DNA Copy Number Variations
  • Female
  • Gene Deletion
  • Gene Expression Profiling / methods*
  • Gene Expression Regulation, Neoplastic
  • Genomics / methods*
  • Humans
  • Mutation
  • Neoplasm Metastasis
  • Prognosis
  • Receptor, ErbB-2 / genetics*
  • Triple Negative Breast Neoplasms / classification*
  • Triple Negative Breast Neoplasms / genetics

Substances

  • Biomarkers, Tumor
  • CDKN2A protein, human
  • Cyclin-Dependent Kinase Inhibitor p16
  • Class I Phosphatidylinositol 3-Kinases
  • PIK3CA protein, human
  • ERBB2 protein, human
  • Receptor, ErbB-2