The immune system and response to HER2-targeted treatment in breast cancer

Lancet Oncol. 2014 Feb;15(2):e58-68. doi: 10.1016/S1470-2045(13)70477-7.


The monoclonal antibody trastuzumab targets the growth factor receptor HER2 and has profoundly improved the course of disease and survival of women with HER2-overexpressing breast cancer. Because trastuzumab targets aberrant expression of HER2 in tumours addicted to HER2 activation, its clinical activity is credited largely to inhibition of intracellular signalling. A growing body of preclinical and clinical evidence shows that the immune system contributes substantially to the therapeutic effects of trastuzumab and other monoclonal antibodies in vivo. Furthermore, findings indicate that immune-related markers can provide useful predictive information and that increased clinical activity might follow activation of the immune system. Development of immunomodulatory drugs with remarkable activity in many solid tumours defines a scenario in which the combination of immune modulation with trastuzumab, or other HER2-directed drugs, will result in augmented response and clinical outcome.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adaptive Immunity / drug effects
  • Animals
  • Antibodies, Monoclonal, Humanized / therapeutic use*
  • Antineoplastic Agents / therapeutic use*
  • Breast Neoplasms / enzymology
  • Breast Neoplasms / immunology
  • Breast Neoplasms / pathology
  • Breast Neoplasms / therapy*
  • Female
  • Humans
  • Immunotherapy* / methods
  • Molecular Targeted Therapy*
  • Receptor, ErbB-2 / antagonists & inhibitors*
  • Receptor, ErbB-2 / immunology
  • Receptor, ErbB-2 / metabolism
  • Signal Transduction / drug effects
  • Trastuzumab
  • Treatment Outcome


  • Antibodies, Monoclonal, Humanized
  • Antineoplastic Agents
  • ERBB2 protein, human
  • Receptor, ErbB-2
  • Trastuzumab