Triple negative breast cancer: from molecular portrait to therapeutic intervention

Crit Rev Eukaryot Gene Expr. 2010;20(1):17-34. doi: 10.1615/critreveukargeneexpr.v20.i1.20.

Abstract

Triple negative breast cancer is a subtype of breast cancer that lacks expression of an estrogen receptor (ER), a progesterone receptor (PR), and HER2. It is characterized by its unique molecular profile, aggressive behavior, and distinct pattern of metastasis. Epidemiological studies show a high prevalence of triple negative breast cancer among younger women and those of African descent. Although sensitive to chemotherapy, early relapse is common, and a predilection for visceral metastasis, including brain metastasis, has been described. Gene-expression profiling approaches demonstrated that triple negative breast cancer is a heterogeneous group of diseases composed of different, molecularly distinct subtypes. Although not synonymous, the majority of triple negative breast cancers carry the "basal-like" molecular profile on gene-expression arrays. However, several studies have shown that triple negative breast cancer includes tumors with a non-basal expression profile and, in particular, the "normal-breast," the "multiple marker negative," and the recently identified "claudin-negative" subtypes. Target-based agents, including epidermal growth factor receptor (EGFR), vascular endothelial growth factor (VEGF), and poly-ADP-ribose polymerase (PARP) inhibitors, are currently in clinical trials and hold promise in the treatment of this aggressive disease.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / pathology
  • Chromosome Mapping
  • Comparative Genomic Hybridization
  • Female
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic
  • Genes, erbB-2
  • Humans
  • Neoplastic Stem Cells / pathology
  • Receptor, ErbB-2 / deficiency*
  • Receptor, ErbB-2 / genetics
  • Receptors, Estrogen / deficiency*
  • Receptors, Estrogen / genetics
  • Receptors, Progesterone / deficiency*
  • Receptors, Progesterone / genetics

Substances

  • Receptors, Estrogen
  • Receptors, Progesterone
  • Receptor, ErbB-2