Therapeutic options for triple-negative breast cancers with defective homologous recombination

Biochim Biophys Acta. 2009 Dec;1796(2):266-80. doi: 10.1016/j.bbcan.2009.07.001. Epub 2009 Jul 17.

Abstract

Breast cancer is the most common malignancy among women in developed countries, affecting more than a million women per year worldwide. Over the last decades, our increasing understanding of breast cancer biology has led to the development of endocrine agents against hormone receptor-positive tumors and targeted therapeutics against HER2-expressing tumors. However, no targeted therapy is available for patients with triple-negative breast cancer, lacking expression of hormone receptors and HER2. Overlap between BRCA1-mutated breast cancers and triple-negative tumors suggests that an important part of the triple-negative tumors may respond to therapeutics targeting BRCA1-deficient cells. Here, we review the features shared between triple-negative, basal-like and BRCA1-related breast cancers. We also discuss the development of novel therapeutic strategies to target BRCA1-mutated tumors and triple-negative tumors with BRCA1-like features. Finally, we highlight the utility of mouse models for BRCA1-mutated breast cancer to optimize (combination) therapy and to understand drug resistance.

Publication types

  • Review

MeSH terms

  • Animals
  • Breast Neoplasms / chemistry*
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / genetics
  • Breast Neoplasms / pathology
  • Cell Cycle
  • DNA Repair
  • Disease Models, Animal
  • Drug Resistance, Neoplasm
  • Female
  • Genes, BRCA1
  • Humans
  • Mice
  • Mutation
  • Poly(ADP-ribose) Polymerase Inhibitors
  • Protein Kinase Inhibitors / therapeutic use
  • Receptor, ErbB-2 / analysis*
  • Receptors, Estrogen / analysis*
  • Receptors, Progesterone / analysis*
  • Recombination, Genetic*

Substances

  • Poly(ADP-ribose) Polymerase Inhibitors
  • Protein Kinase Inhibitors
  • Receptors, Estrogen
  • Receptors, Progesterone
  • ERBB2 protein, human
  • Receptor, ErbB-2