Emerging drugs targeting human epidermal growth factor receptor 2 (HER2) in the treatment of breast cancer

Expert Opin Emerg Drugs. 2016;21(1):91-101. doi: 10.1517/14728214.2016.1146680. Epub 2016 Feb 16.

Abstract

Introduction: Human epidermal growth factor 2 (HER2) overexpression is present in 20% of breast cancer patients. It is associated with more aggressive disease and worse clinical outcome. New drugs are thus needed. Approved and future treatments will be discussed in this review.

Areas covered: The monoclonal antibodies trastuzumab and pertuzumab, the tyrosine kinase inhibitor lapatinib and the antibody-drug conjugate trastuzmab emtansine are approved for HER2 positive breast cancer. The combination of trastuzumab, pertuzumab and docetaxel is currently the first-line treatment in the metastatic setting. New therapies are still needed due to frequent relapse and resistance. These include mammalian target of rapamycin inhibitors, heat shock protein 90 inhibitors, pan-HER2 tyrosine kinase inhibitors, antibody-drug conjugates, immunotherapy agents (antibodies and vaccines), radioimmunotherapy and HER2 specific affinity proteins. Possible developmental issues are the complexity of the molecular biology of the HER2 positive cancer cell, the occurrence of resistance, toxicity and the high cost.

Expert opinion: The determination of the right sequence of use of old and new therapies remains a challenging issue. The selection of patients who do or don't benefit from potentially toxic chemotherapy is also difficult. Central nervous system metastases are a common problem in HER2 positive breast cancer that needs to be addressed in future trials.

Keywords: HER2; antibody drug conjugates; breast cancer; monoclonal antibodies; tyrosine kinase inhibitors.

Publication types

  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use*
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / genetics
  • Breast Neoplasms / pathology
  • Drug Design
  • Drug Resistance, Neoplasm
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Molecular Targeted Therapy
  • Neoplasm Metastasis
  • Neoplasm Recurrence, Local
  • Patient Selection
  • Receptor, ErbB-2 / genetics*

Substances

  • Antineoplastic Agents
  • ERBB2 protein, human
  • Receptor, ErbB-2