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Cardiotoxicity of anticancer treatments

A Corrigendum to this article was published on 20 August 2015

This article has been updated

Key Points

  • The effects of cancer treatment may become clinically apparent only after cardiac reserves have been depleted and a reduction in function can be measured

  • The tools used to measure cardiac function are imperfect with regard to both sensitivity and specificity and can result in over-appreciation or under-appreciation of treatment-related toxicity

  • Anthracyclines, in contrast to agents that inhibit or interfere with tyrosine kinases, cause myocyte injury that is dose-related and cumulative, limiting the safe lifetime exposure

  • Chemotherapy-related cardiotoxicity can be prevented and the late effects mitigated through primary cardioprotection and early initiation of treatment for compromised cardiac function

  • Radiation can cause intimal damage and atherogenesis, which can lead to ischaemia presenting years or decades after exposure; small vessel disease can compromise cardiac contractility

  • Radiation-induced injury to the pericardium might be an early or late manifestation, and injury to the valves and conduction system might present years or decades after exposure

Abstract

Patients with cancer can experience adverse cardiovascular events secondary to the malignant process itself or its treatment. Patients with cancer might also have underlying cardiovascular illness, the consequences of which are often exacerbated by the stress of the tumour growth or its treatment. With the advent of new treatments and subsequent prolonged survival time, late effects of cancer treatment can become clinically evident decades after completion of therapy. The heart's extensive energy reserve and its ability to compensate for reduced function add to the complexity of diagnosis and timely initiation of therapy. Additionally, modern oncological treatment regimens often incorporate multiple agents whose deleterious cardiac effects might be additive or synergistic. Treatment-related impairment of cardiac contractility can be either transient or irreversible. Furthermore, cancer treatment is associated with life-threatening arrhythmia, ischaemia, infarction, and damage to cardiac valves, the conduction system, or the pericardium. Awareness of these processes has gained prominence with the arrival of strategies to monitor and to prevent or to mitigate the effects of cardiovascular damage. A greater understanding of the mechanisms of injury can prolong the lives of those cured of their malignancy, but left with potentially devastating cardiac sequelae.

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Figure 1: The correlation between cumulative doxorubicin dose and the incidence of CHF.
Figure 2: Simplified pathway depicting the presumed interaction between anthracycline and trastuzumab.

Change history

  • 20 August 2015

    In the version of this article initially published online and in print, trastuzumab was incorrectly defined as a tyrosine kinase inhibitor. This error has been corrected for the HTML and PDF versions of the article.

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Acknowledgements

The authors thank Professor Debu Tripathy, Chairman of the Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, for his valuable comments and for his critical review of this manuscript.

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Correspondence to Michael S. Ewer.

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Ewer, M., Ewer, S. Cardiotoxicity of anticancer treatments. Nat Rev Cardiol 12, 547–558 (2015). https://doi.org/10.1038/nrcardio.2015.65

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