Triple-negative breast cancer: is there a treatment on the horizon?

Oncotarget. 2017 Jan 3;8(1):1913-1924. doi: 10.18632/oncotarget.12284.

Abstract

Triple-negative breast cancer (TNBC), which accounts for 15-20% of all breast cancers, does not express estrogen receptor (ER) or progesterone receptor (PR) and lacks human epidermal growth factor receptor 2 (HER2) overexpression or amplification. These tumors have a more aggressive phenotype and a poorer prognosis due to the high propensity for metastatic progression and absence of specific targeted treatments. Patients with TNBC do not benefit from hormonal or trastuzumab-based targeted therapies because of the loss of target receptors. Although these patients respond to chemotherapeutic agents such as taxanes and anthracyclines better than other subtypes of breast cancer, prognosis remains poor. A group of targeted therapies under investigation showed favorable results in TNBC, especially in cancers with BRCA mutation. The lipid-lowering statins (3-hydroxy-3-methyl-glutaryl coenzyme A reductase inhibitors), including lovastatin and simvastatin, have been shown to preferentially target TNBC compared with non-TNBC. These statins hold great promise for the management of TNBC. Only with the understanding of the molecular basis for the preference of statins for TNBC and more investigations in clinical trials can they be reformulated into a clinically approved drug against TNBC.

Keywords: breast cancer; therapeutics; triple-negative.

Publication types

  • Review

MeSH terms

  • Anthracyclines / therapeutic use
  • Antineoplastic Agents / therapeutic use*
  • BRCA1 Protein / genetics*
  • BRCA2 Protein / genetics*
  • Female
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / therapeutic use*
  • Lovastatin / therapeutic use*
  • Molecular Targeted Therapy / methods
  • Receptor, ErbB-2 / metabolism
  • Receptors, Estrogen / metabolism
  • Receptors, Progesterone / metabolism
  • Simvastatin / therapeutic use*
  • Taxoids / therapeutic use
  • Triple Negative Breast Neoplasms / drug therapy*
  • Triple Negative Breast Neoplasms / genetics*
  • Triple Negative Breast Neoplasms / mortality

Substances

  • Anthracyclines
  • Antineoplastic Agents
  • BRCA1 Protein
  • BRCA1 protein, human
  • BRCA2 Protein
  • BRCA2 protein, human
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Receptors, Estrogen
  • Receptors, Progesterone
  • Taxoids
  • Lovastatin
  • Simvastatin
  • ERBB2 protein, human
  • Receptor, ErbB-2