Trastuzumab cardiotoxicity: Biological hypotheses and clinical open issues

Emilio Bria, Federica Cuppone, Michele Milella, Sunil Verma, Paolo Carlini, Cecilia Nisticò, Vanja Vaccaro, Antonio Rossi, Giuseppe Tonini, Francesco Cognetti, Edmondo Terzoli

Research output: Contribution to journalArticle


Background: Trastuzumab has significantly improved the prognosis of breast cancer patients overexpressing the human epidermal growth factor receptor 2 (HER2). This result has been achieved in all disease settings, by increasing overall survival in early stage and advanced disease and by increasing pathological complete responses in neoadjuvant disease. Objective: Although the greatest impact of this monoclonal antibody has been seen in the adjuvant setting, by increasing disease-free survival and overall survival rates an increased rate of both symptomatic and nonsymptomatic cardiac toxicity has also been observed. Methods: In the following review, the different mechanisms of trastuzumab cardiac toxicity are described and, in addition, the clinical data coming from both trials and meta-analyses is discussed. Results: While there is strong evidence for the incidence of trastuzumab-related cardiac toxicity, there is still little known on the exact pathogenesis of this toxicity. Interestingly, both experimental and clinical data suggest that trastuzumab may sensitize cardiomyocytes to injuries and stress from administration of anthracyclines. This has led to a proposed novel mechanism of cardiotoxicity that appears to be quite different from the anthracycline-associated cardiotoxicity. Trastuzumab does not seem to cause any overt ultrastructural abnormality; it does, however, lead to myocardial dysfunction. Conclusion: Most of the proposed hypotheses seems to be related to the activity of trastuzumab in interfering with the ERBB-2 receptor. Indeed, data from clinical trials in the adjuvant setting report increased cardiac toxicity in those patients who previously received anthracyclines.

Original languageEnglish
Pages (from-to)1963-1971
Number of pages9
JournalExpert Opinion on Biological Therapy
Issue number12
Publication statusPublished - Dec 2008


  • Cardiotoxicity
  • Review
  • Trastuzumab

ASJC Scopus subject areas

  • Pharmacology
  • Clinical Biochemistry
  • Drug Discovery

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  • Cite this

    Bria, E., Cuppone, F., Milella, M., Verma, S., Carlini, P., Nisticò, C., Vaccaro, V., Rossi, A., Tonini, G., Cognetti, F., & Terzoli, E. (2008). Trastuzumab cardiotoxicity: Biological hypotheses and clinical open issues. Expert Opinion on Biological Therapy, 8(12), 1963-1971.