Tackling intra- and inter-tumor heterogeneity to combat triple negative breast cancer

Front Biosci (Landmark Ed). 2017 Jun 1;22:1549-1580. doi: 10.2741/4558.


Rampant inter-patient and intra-tumor heterogeneity present formidable challenges in the clinical management of triple-negative breast cancer (TNBC) and mandate a "divide-and-conquer" approach wherein deep biomarker profiling drives patient segmentation and development of customized treatments. Genomic and proteomic studies have uncovered several TNBC subtypes each of which represents a distinct disease pathobiology and harbors unique actionable targets that may illuminate sensitivities to specific classes of therapeutics. This review details the mind-boggling complexity of TNBC, its ramifications for prognosis and therapeutic response, and discusses what treatments might befit each TNBC subtype. Additionally, focused efforts geared toward translating these findings into the clinic are urged. This review also supports an evidence-based paradigm shift towards inclusion of agents that target the mechanisms that drive intra-tumor heterogeneity, in order to improve long-term outcomes for TNBC patients.

Publication types

  • Review

MeSH terms

  • Antineoplastic Agents / therapeutic use*
  • Female
  • Gene Expression Profiling / methods*
  • Gene Expression Regulation, Neoplastic*
  • Genetic Heterogeneity / drug effects
  • Humans
  • Molecular Targeted Therapy / methods
  • Molecular Targeted Therapy / trends
  • Prognosis
  • Proteomics / methods*
  • Triple Negative Breast Neoplasms / drug therapy*
  • Triple Negative Breast Neoplasms / genetics
  • Triple Negative Breast Neoplasms / metabolism


  • Antineoplastic Agents