Cardiotoxicity associated with trastuzumab treatment of HER2+ breast cancer

Adv Ther. 2009 Jul:26 Suppl 1:S9-17. doi: 10.1007/s12325-009-0048-z. Epub 2009 Jul 24.

Abstract

Introduction: Although having high clinical efficacy in the treatment of human epidermal growth factor receptor-2 (HER2+) metastatic breast cancer, trastuzumab has been associated with cardiotoxicity, and the etiology and pathogenesis of this condition is currently under investigation.

Methods: This paper reviews the cardiotoxicity, associated with trastuzumab use and discusses the risk assessment and management of cardiac dysfunction.

Results: The increased risk of cardiotoxicity is lower when trastuzumab is given as monotherapy (3%-7%) compared with anthracyclines + trastuzumab therapy (27%). Type II cardiac changes occur in trastuzumab-treated patients, which do not appear to be dose-related, are not associated with histological changes, and are generally reversible. Several risk factors for cardiac events have been identified and assessing levels of troponin I and N-terminal pro-brain B-type natriuretic peptide before and after treatment with trastuzumab may allow early detection of cardiotoxicity. A symptomatic and functional evaluation scheme for patients indicated for treatment with trastuzumab has also been proposed to work alongside therapeutic options for the treatment of heart failure.

Conclusion: The risk of cardiac dysfunction associated with trastuzumab can be justified given the increase in overall survival. This risk is lower when trastuzumab is given as monotherapy. The paradigm for cardiologists remains the same: treat the cancer effectively whilst preventing cardiotoxicity.

Publication types

  • Review

MeSH terms

  • Antibodies, Monoclonal / adverse effects*
  • Antibodies, Monoclonal / therapeutic use
  • Antibodies, Monoclonal, Humanized
  • Antineoplastic Agents / adverse effects*
  • Antineoplastic Agents / therapeutic use
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / metabolism
  • Cardiovascular Agents / therapeutic use
  • Cardiovascular Diseases / chemically induced*
  • Cardiovascular Diseases / physiopathology
  • Erb-b2 Receptor Tyrosine Kinases / biosynthesis*
  • Female
  • Humans
  • Natriuretic Peptide, Brain / blood
  • Peptide Fragments / blood
  • Risk Factors
  • Stroke Volume
  • Trastuzumab
  • Troponin I / blood

Substances

  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Antineoplastic Agents
  • Cardiovascular Agents
  • Natriuretic Peptide, Brain
  • Peptide Fragments
  • Erb-b2 Receptor Tyrosine Kinases
  • Trastuzumab
  • Troponin I
  • pro-brain natriuretic peptide (1-76)