Triple-negative breast cancer: challenges and opportunities of a heterogeneous disease

Nat Rev Clin Oncol. 2016 Nov;13(11):674-690. doi: 10.1038/nrclinonc.2016.66. Epub 2016 May 17.

Abstract

Chemotherapy is the primary established systemic treatment for patients with triple-negative breast cancer (TNBC) in both the early and advanced-stages of the disease. The lack of targeted therapies and the poor prognosis of patients with TNBC have fostered a major effort to discover actionable molecular targets to treat patients with these tumours. Massively parallel sequencing and other 'omics' technologies have revealed an unexpected level of heterogeneity of TNBCs and have led to the identification of potentially actionable molecular features in some TNBCs, such as germline BRCA1/2 mutations or 'BRCAness', the presence of the androgen receptor, and several rare genomic alterations. Whether these alterations are molecular 'drivers', however, has not been clearly established. A subgroup of TNBCs shows a high degree of tumour-infiltrating lymphocytes that also correlates with a lower risk of disease relapse and a higher likelihood of benefit from chemotherapy. Proof-of-principle studies with immune-checkpoint inhibitors in advanced-stage TNBC have yielded promising results, indicating the potential benefit of immunotherapy for patients with TNBC. In this Review, we discuss the most relevant molecular findings in TNBC from the past decade and the most promising therapeutic opportunities derived from these data.

Publication types

  • Review

MeSH terms

  • Androgen Antagonists / therapeutic use
  • BRCA2 Protein / genetics
  • Biomarkers, Tumor / metabolism
  • Clinical Trials as Topic
  • Female
  • Humans
  • Immune System / immunology
  • Immunotherapy / methods*
  • Mitogen-Activated Protein Kinases / antagonists & inhibitors
  • Molecular Targeted Therapy / methods*
  • Mutation / genetics
  • Neoplastic Stem Cells / drug effects
  • Phosphoinositide-3 Kinase Inhibitors
  • Poly(ADP-ribose) Polymerase Inhibitors / therapeutic use
  • Prognosis
  • Triple Negative Breast Neoplasms / classification
  • Triple Negative Breast Neoplasms / genetics
  • Triple Negative Breast Neoplasms / therapy*
  • Ubiquitin-Protein Ligases / genetics

Substances

  • Androgen Antagonists
  • BRCA2 Protein
  • BRCA2 protein, human
  • Biomarkers, Tumor
  • Phosphoinositide-3 Kinase Inhibitors
  • Poly(ADP-ribose) Polymerase Inhibitors
  • BRAP protein, human
  • Ubiquitin-Protein Ligases
  • Mitogen-Activated Protein Kinases