title: Molecular heterogeneity of triple-negative breast cancer and its clinical implications.
abstract: OBJECTIVE
  Triple-negative breast cancer (TNBC) is defined by a lack of expression of hormone receptors, oestrogen and progesterone, as well as human epidermal factor receptor 2. This review focuses on the increasing understanding of the molecular heterogeneity of TNBC subtypes and the therapeutic implications of this subclassification.
  
  
  RESULTS
  Emerging evidence clearly indicates that TNBC is a heterogeneous disease with varying prognosis according to clinical, pathological and genetic factors. Some distinct histological special types within this clinically defined collection of entities have been shown to have a particularly good prognosis (e.g. medullary carcinomas), and others very poor outcome (e.g. metaplastic carcinomas), whereas the broader immunohistochemically defined 'core-basal-like' or gene expression defined 'basal' groups generally have a poor prognosis. This molecular subclassification has implicated several biological processes as potential therapeutic targets: the DNA damage response, drivers of deregulated proliferation, angiogenesis, epithelial-mesenchymal transition and immune deregulation.
  
  
  CONCLUSIONS
  Molecular stratification of these prognostic groups has been critical in identifying novel therapeutic targets for future drug development. The development of poly-(ADP)ribose polymerase inhibitors for BRCA1-mutation carriers with TNBC has led the ongoing efforts to translate fundamental biological insights into improved therapies for a difficult-to-treat breast cancer subgroup.
authors: Breakthrough Breast Cancer Research Unit, Research Oncology, Kings College London School of Medicine, Kings Health Partners AHSC, London, UK.
authors: Sheeba
authors: S
authors: Irshad
authors: Paul
authors: P
authors: Ellis
authors: Andrew
authors: A
authors: Tutt
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000628:therapy; D005260:Female; D006801:Humans; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000096:biosynthesis* / Q000172:deficiency; D011960:Receptors, Estrogen / Q000096:biosynthesis* / Q000172:deficiency; D011980:Receptors, Progesterone / Q000096:biosynthesis* / Q000172:deficiency
chemical_list: D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone