New therapies in HER2-positive breast cancer: a major step towards a cure of the disease?

Cancer Treat Rev. 2012 Aug;38(5):494-504. doi: 10.1016/j.ctrv.2012.01.001. Epub 2012 Feb 3.

Abstract

Overexpression of the human epidermal growth factor receptor 2 (HER2) predicts a poor prognosis in metastatic breast cancer. While the introduction of HER2-targeted therapies, such as the monoclonal antibody trastuzumab and the small-molecule tyrosine kinase inhibitor lapatinib, has significantly improved outcomes in HER2+ breast cancer compared with previously available therapies, use of these targeted therapies is often limited by the development of drug resistance and tolerability issues. These limitations create the need for further development and investigation of new targeted therapies that show potent and selective inhibition of these targets or closely connected molecular pathways. Recently, several agents have demonstrated promising activity in HER2+ metastatic breast cancer, either as monotherapy or in combination therapy, including the tyrosine-kinase inhibitors neratinib (HKI-272) and afatinib (BIBW-2992) and the anti-HER2 monoclonal antibodies pertuzumab and trastuzumab-DM1 (T-DM1). Agents that target other molecular pathways, such as the vascular endothelial growth factor receptor, mammalian target of rapamycin, PI3-kinases, insulin-like growth factor (IGFR), HSP-90, and other kinases also have potential, in combination with anti-HER2 and/or other systemic therapies, to be active in this subtype of breast cancer. Innovative clinical studies are required in well-characterized patient populations to define the true clinical value of these emerging new approaches.

Publication types

  • Review

MeSH terms

  • Afatinib
  • Antibodies, Monoclonal / therapeutic use*
  • Antibodies, Monoclonal, Humanized / pharmacology
  • Antibodies, Monoclonal, Humanized / therapeutic use
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / pathology
  • Female
  • Humans
  • Lapatinib
  • Protein Kinase Inhibitors / therapeutic use*
  • Quinazolines / therapeutic use
  • Quinolines / therapeutic use
  • Receptor, ErbB-2 / metabolism*
  • Trastuzumab

Substances

  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Protein Kinase Inhibitors
  • Quinazolines
  • Quinolines
  • Lapatinib
  • Afatinib
  • ERBB2 protein, human
  • Receptor, ErbB-2
  • neratinib
  • pertuzumab
  • Trastuzumab