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Cancer treatment-related cardiac toxicity: prevention, assessment and management

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Abstract

Cancer therapies, especially anthracyclines and monoclonal antibodies, have been linked with increased rates of cardiotoxicity. The development of some cardiac side effects happens over several months, and changes in ejection fraction can be detected long before permanent damage or disability occurs. Advanced heart failure could be averted with better and earlier detection. Methodologies for early detection of cardiac changes include stress echocardiograms, cardiac velocity measurements, radionuclide imaging, cardiac MRI and several potential biomarkers. Many agents have been described for prophylaxis of cardiac events precipitated by cancer therapy. Prophylactic use of beta-blockers and ACE inhibitors may be considered for use with trastuzumab in breast cancer as tolerated. Recovery of cardiac function is possible early after the injury from a cancer therapy. Late complications for coronary artery disease, hypertension and arrhythmia are underappreciated. Treatments for severe cancer therapy-related cardiac complications follow the existing paradigms for congestive heart failure and coronary artery disease, although outcomes for cancer patients differ from outcomes for non-cancer patients.

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References

  1. Thavendiranathan P, et al. Breast cancer therapy-related cardiac dysfunction in adult women treated in routine clinical practice: a population-based cohort study. J Clin Oncol. 2016;34(19):2239–46.

    Article  PubMed  Google Scholar 

  2. Di Marco A, Cassinelli G, Arcamone F. The discovery of daunorubicin. Cancer Treat Rep. 1981;65(Suppl 4):3–8.

    PubMed  Google Scholar 

  3. Amiri-Kordestani L, et al. First FDA approval of neoadjuvant therapy for breast cancer: pertuzumab for the treatment of patients with HER2-positive breast cancer. Clin Cancer Res. 2014;20(21):5359–64.

    Article  CAS  PubMed  Google Scholar 

  4. Geisberg CA, Sawyer DB. Mechanisms of anthracycline cardiotoxicity and strategies to decrease cardiac damage. Curr Hypertens Rep. 2010;12(6):404–10.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Guglin M, et al. Introducing a new entity: chemotherapy-induced arrhythmia. Europace. 2009;11(12):1579–86.

    Article  PubMed  Google Scholar 

  6. Curigliano G, et al. Cardiotoxicity of anticancer treatments: epidemiology, detection, and management. CA Cancer J Clin. 2016. doi:10.3322/caac.21341.

  7. Haque R, et al. Cardiovascular disease after aromatase inhibitor use. JAMA Oncol. 2016. doi:10.1001/jamaoncol.2016.0429.

  8. Khan NF, et al. Long-term health outcomes in a British cohort of breast, colorectal and prostate cancer survivors: a database study. Br J Cancer. 2011;105(Suppl 1):S29–37.

    Article  PubMed  PubMed Central  Google Scholar 

  9. Nathan PC, Amir E, Abdel-Qadir H. Cardiac outcomes in survivors of pediatric and adult cancers. Can J Cardiol. 2016;32(7):871–80.

    Article  PubMed  Google Scholar 

  10. Jones RL, Swanton C, Ewer MS. Anthracycline cardiotoxicity. Expert Opin Drug Saf. 2006;5(6):791–809.

    Article  CAS  PubMed  Google Scholar 

  11. Gaudin PB, et al. Myocarditis associated with doxorubicin cardiotoxicity. Am J Clin Pathol. 1993;100(2):158–63.

    Article  CAS  PubMed  Google Scholar 

  12. Von Hoff DD, et al. Risk factors for doxorubicin-induced congestive heart failure. Ann Intern Med. 1979;91(5):710–7.

    Article  Google Scholar 

  13. Lefrak EA, et al. A clinicopathologic analysis of adriamycin cardiotoxicity. Cancer. 1973;32(2):302–14.

    Article  CAS  PubMed  Google Scholar 

  14. Mulrooney DA, et al. Cardiac outcomes in a cohort of adult survivors of childhood and adolescent cancer: retrospective analysis of the Childhood Cancer Survivor Study cohort. BMJ. 2009;339:b4606.

    Article  PubMed  PubMed Central  Google Scholar 

  15. Slamon DJ, et al. Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2. N Engl J Med. 2001;344(11):783–92.

    Article  CAS  PubMed  Google Scholar 

  16. Mantarro S, et al. Risk of severe cardiotoxicity following treatment with trastuzumab: a meta-analysis of randomized and cohort studies of 29,000 women with breast cancer. Intern Emerg Med. 2016;11(1):123–40.

    Article  PubMed  Google Scholar 

  17. Wittayanukorn S, et al. Cardiotoxicity in targeted therapy for breast cancer: a study of the FDA adverse event reporting system (FAERS). J Oncol Pharm Pract. 2015. doi:10.1177/1078155215621150.

  18. Qi WX, et al. Bevacizumab increases the risk of severe congestive heart failure in cancer patients: an up-to-date meta-analysis with a focus on different subgroups. Clin Drug Investig. 2014;34(10):681–90.

    Article  CAS  PubMed  Google Scholar 

  19. Chen Z, Ai D. Cardiotoxicity associated with targeted cancer therapies. Mol Clin Oncol. 2016;4(5):675–81.

    PubMed  PubMed Central  Google Scholar 

  20. Zambetti M, et al. Long-term cardiac sequelae in operable breast cancer patients given adjuvant chemotherapy with or without doxorubicin and breast irradiation. J Clin Oncol. 2001;19(1):37–43.

    CAS  PubMed  Google Scholar 

  21. Favourable and unfavourable effects on long-term survival of radiotherapy for early breast cancer: an overview of the randomised trials. Early Breast Cancer Trialists’ Collaborative Group. Lancet. 2000;355(9217):1757–70.

  22. Hasan S, et al. Doxorubicin cardiotoxicity in African Americans. J Natl Med Assoc. 2004;96(2):196–9.

    PubMed  PubMed Central  Google Scholar 

  23. Szmit S, et al. Pre-existing arterial hypertension as a risk factor for early left ventricular systolic dysfunction following (R)-CHOP chemotherapy in patients with lymphoma. J Am Soc Hypertens. 2014;8(11):791–9.

    Article  PubMed  Google Scholar 

  24. da Fonseca LG, et al. Cardiac safety of (neo)adjuvant trastuzumab in the community setting: a single-center experience. Breast Care (Basel). 2014;9(4):255–60.

    Google Scholar 

  25. Pizzuti L, et al. Neoadjuvant sequential docetaxel followed by high-dose epirubicin in combination with cyclophosphamide administered concurrently with trastuzumab: the DECT trial. J Cell Physiol. 2016. doi:10.1002/jcp.25432.

  26. Cascales A, et al. Association of anthracycline-related cardiac histological lesions with NADPH oxidase functional polymorphisms. Oncologist. 2013;18(4):446–53.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Stoddard MF, et al. Prolongation of isovolumetric relaxation time as assessed by Doppler echocardiography predicts doxorubicin-induced systolic dysfunction in humans. J Am Coll Cardiol. 1992;20(1):62–9.

    Article  CAS  PubMed  Google Scholar 

  28. Schwartz RG, et al. Congestive heart failure and left ventricular dysfunction complicating doxorubicin therapy. Seven-year experience using serial radionuclide angiocardiography. Am J Med. 1987;82(6):1109–18.

    Article  CAS  PubMed  Google Scholar 

  29. Piotrowski G, et al. Role of echocardiography in monitoring of cardiac toxicity of cancer pharmacotherapy. Expert consensus statement of the Polish clinical forum for cardiovascular imaging. Kardiol Pol. 2014;72(6):558–75.

    Article  PubMed  Google Scholar 

  30. Gavila J, et al. Evaluation and management of chemotherapy-induced cardiotoxicity in breast cancer: a Delphi study. Clin Transl Oncol. 2016. doi:10.1007/s12094-016-1508-y.

  31. Truong SR, et al. Evaluating the utility of baseline cardiac function screening in early-stage breast cancer treatment. Oncologist. 2016;21(6):666–70.

    Article  PubMed  Google Scholar 

  32. Yoon GJ, et al. Left ventricular dysfunction in patients receiving cardiotoxic cancer therapies are clinicians responding optimally? J Am Coll Cardiol. 2010;56(20):1644–50.

    Article  PubMed  Google Scholar 

  33. Karabay CY, et al. Mitral regurgitation due to papillary muscle dyssynchrony during trastuzumab treatment. Cardiology. 2010;117(4):296–300.

    Article  PubMed  Google Scholar 

  34. Jiji RS, Kramer CM, Salerno M. Non-invasive imaging and monitoring cardiotoxicity of cancer therapeutic drugs. J Nucl Cardiol. 2012;19(2):377–88.

    Article  PubMed  PubMed Central  Google Scholar 

  35. Guendouz S, et al. Restrictive cardiomyopathy associated with left ventricle and left atria endocardial calcifications following chemotherapy. J Am Coll Cardiol. 2011;57(15):1633.

    Article  PubMed  Google Scholar 

  36. Bayram C, et al. Evaluation of cardiotoxicity by tissue Doppler imaging in childhood leukemia survivors treated with low-dose anthracycline. Pediatr Cardiol. 2015;36(4):862–6.

    Article  PubMed  Google Scholar 

  37. Karakurt C, Kocak G, Ozgen U. Evaluation of the left ventricular function with tissue tracking and tissue Doppler echocardiography in pediatric malignancy survivors after anthracycline therapy. Echocardiography. 2008;25(8):880–7.

    Article  PubMed  Google Scholar 

  38. Mavinkurve-Groothuis AM, et al. Myocardial strain and strain rate in monitoring subclinical heart failure in asymptomatic long-term survivors of childhood cancer. Ultrasound Med Biol. 2010;36(11):1783–91.

    Article  PubMed  Google Scholar 

  39. Fallah-Rad N, et al. The utility of cardiac biomarkers, tissue velocity and strain imaging, and cardiac magnetic resonance imaging in predicting early left ventricular dysfunction in patients with human epidermal growth factor receptor II-positive breast cancer treated with adjuvant trastuzumab therapy. J Am Coll Cardiol. 2011;57(22):2263–70.

    Article  CAS  PubMed  Google Scholar 

  40. Lunning MA, et al. Cardiac magnetic resonance imaging for the assessment of the myocardium after doxorubicin-based chemotherapy. Am J Clin Oncol. 2015;38(4):377–81.

    Article  CAS  PubMed  Google Scholar 

  41. de Ville de Goyet M, et al. Prospective cardiac MRI for the analysis of biventricular function in children undergoing cancer treatments. Pediatr Blood Cancer. 2015;62(5):867–74.

    Article  PubMed  Google Scholar 

  42. Ryerson AB, et al. Assessing anthracycline-treated childhood cancer survivors with advanced stress echocardiography. Pediatr Blood Cancer. 2015;62(3):502–8.

    Article  CAS  PubMed  Google Scholar 

  43. Henri C, Heinonen T, Tardif JC. The role of biomarkers in decreasing risk of cardiac toxicity after cancer therapy. Biomark Cancer. 2016;8(Suppl 2):39–45.

    Article  PubMed  PubMed Central  Google Scholar 

  44. Lenihan DJ, et al. The utility of point-of-care biomarkers to detect cardiotoxicity during anthracycline chemotherapy: a feasibility study. J Card Fail. 2016;22(6):433–8.

    Article  CAS  PubMed  Google Scholar 

  45. Putt M, et al. Longitudinal changes in multiple biomarkers are associated with cardiotoxicity in breast cancer patients treated with doxorubicin, taxanes, and trastuzumab. Clin Chem. 2015;61(9):1164–72.

    Article  CAS  PubMed  Google Scholar 

  46. Katsurada K, et al. High-sensitivity troponin T as a marker to predict cardiotoxicity in breast cancer patients with adjuvant trastuzumab therapy. Springerplus. 2014;3:620.

    Article  PubMed  PubMed Central  Google Scholar 

  47. De Iuliis F, et al. Serum biomarkers evaluation to predict chemotherapy-induced cardiotoxicity in breast cancer patients. Tumour Biol. 2016;37(3):3379–87.

    Article  PubMed  Google Scholar 

  48. Lien MY, et al. Safety and efficacy of pegylated liposomal doxorubicin-based adjuvant chemotherapy in patients with stage I-III triple-negative breast cancer. Anticancer Res. 2014;34(12):7319–26.

    CAS  PubMed  Google Scholar 

  49. O’Brien ME, et al. Reduced cardiotoxicity and comparable efficacy in a phase III trial of pegylated liposomal doxorubicin HCl (CAELYX/Doxil) versus conventional doxorubicin for first-line treatment of metastatic breast cancer. Ann Oncol. 2004;15(3):440–9.

    Article  PubMed  Google Scholar 

  50. Bjelogrlic SK, et al. Activity of d,l-alpha-tocopherol (vitamin E) against cardiotoxicity induced by doxorubicin and doxorubicin with cyclophosphamide in mice. Basic Clin Pharmacol Toxicol. 2005;97(5):311–9.

    Article  CAS  PubMed  Google Scholar 

  51. Berthiaume JM, et al. Dietary vitamin E decreases doxorubicin-induced oxidative stress without preventing mitochondrial dysfunction. Cardiovasc Toxicol. 2005;5(3):257–67.

    Article  CAS  PubMed  Google Scholar 

  52. Wagdi P, et al. Cardioprotection in patients undergoing chemo- and/or radiotherapy for neoplastic disease. A pilot study. Jpn Heart J. 1996;37(3):353–9.

    Article  CAS  PubMed  Google Scholar 

  53. Swain SM, et al. Delayed administration of dexrazoxane provides cardioprotection for patients with advanced breast cancer treated with doxorubicin-containing therapy. J Clin Oncol. 1997;15(4):1333–40.

    CAS  PubMed  Google Scholar 

  54. Pituskin E, et al. Rationale and design of the Multidisciplinary Approach to Novel Therapies in Cardiology Oncology Research Trial (MANTICORE 101-Breast): a randomized, placebo-controlled trial to determine if conventional heart failure pharmacotherapy can prevent trastuzumab-mediated left ventricular remodeling among patients with HER2+ early breast cancer using cardiac MRI. BMC Cancer. 2011;11:318.

    Article  PubMed  PubMed Central  Google Scholar 

  55. Yun S, Vincelette ND, Abraham I. Cardioprotective role of beta-blockers and angiotensin antagonists in early-onset anthracyclines-induced cardiotoxicity in adult patients: a systematic review and meta-analysis. Postgrad Med J. 1081;2015(91):627–33.

    Google Scholar 

  56. Gulati G, et al. Prevention of cardiac dysfunction during adjuvant breast cancer therapy (PRADA): a 2 × 2 factorial, randomized, placebo-controlled, double-blind clinical trial of candesartan and metoprolol. Eur Heart J. 2016;37(21):1671–80.

    Article  PubMed  PubMed Central  Google Scholar 

  57. Pituskin E, Mackey J, Koshman S. MANTICORE 101: multidisciplinary approach to novel therapies in cardio-oncology research. In: San Antonio breast cancer symposium. December 9–12, 2015: San Antonio, TX.

  58. Liu L, et al. Preventive effect of low-dose carvedilol combined with candesartan on the cardiotoxicity of anthracycline drugs in the adjuvant chemotherapy of breast cancer. Zhonghua Zhong Liu Za Zhi. 2013;35(12):936–40.

    CAS  PubMed  Google Scholar 

  59. Georgakopoulos P, et al. Cardioprotective effect of metoprolol and enalapril in doxorubicin-treated lymphoma patients: a prospective, parallel-group, randomized, controlled study with 36-month follow-up. Am J Hematol. 2010;85(11):894–6.

    Article  CAS  PubMed  Google Scholar 

  60. Bosch X, et al. Enalapril and carvedilol for preventing chemotherapy-induced left ventricular systolic dysfunction in patients with malignant hemopathies: the OVERCOME trial (preventiOn of left Ventricular dysfunction with Enalapril and caRvedilol in patients submitted to intensive ChemOtherapy for the treatment of Malignant hEmopathies). J Am Coll Cardiol. 2013;61(23):2355–62.

    Article  CAS  PubMed  Google Scholar 

  61. Seicean S, et al. Effect of statin therapy on the risk for incident heart failure in patients with breast cancer receiving anthracycline chemotherapy: an observational clinical cohort study. J Am Coll Cardiol. 2012;60(23):2384–90.

    Article  CAS  PubMed  Google Scholar 

  62. Acar Z, et al. Efficiency of atorvastatin in the protection of anthracycline-induced cardiomyopathy. J Am Coll Cardiol. 2011;58(9):988–9.

    Article  PubMed  Google Scholar 

  63. Chotenimitkhun R, et al. Chronic statin administration may attenuate early anthracycline-associated declines in left ventricular ejection function. Can J Cardiol. 2015;31(3):302–7.

    Article  PubMed  Google Scholar 

  64. Kalam K, Marwick TH. Role of cardioprotective therapy for prevention of cardiotoxicity with chemotherapy: a systematic review and meta-analysis. Eur J Cancer. 2013;49(13):2900–9.

    Article  CAS  PubMed  Google Scholar 

  65. Akolkar G, et al. The role of renin angiotensin system antagonists in the prevention of doxorubicin and trastuzumab induced cardiotoxicity. Cardiovasc Ultrasound. 2015;13:18.

    Article  PubMed  PubMed Central  Google Scholar 

  66. Cardinale D, et al. Anthracycline-induced cardiomyopathy: clinical relevance and response to pharmacologic therapy. J Am Coll Cardiol. 2010;55(3):213–20.

    Article  CAS  PubMed  Google Scholar 

  67. Ryberg M, et al. Epirubicin cardiotoxicity: an analysis of 469 patients with metastatic breast cancer. J Clin Oncol. 1998;16(11):3502–8.

    CAS  PubMed  Google Scholar 

  68. Ewer MS, et al. Reversibility of trastuzumab-related cardiotoxicity: new insights based on clinical course and response to medical treatment. J Clin Oncol. 2005;23(31):7820–6.

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. UVA Division of Hematology/Oncology, University of Virginia, UVA Box 800716, Charlottesville, VA, 22908, USA

    Ibrahim Fanous & Patrick Dillon

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  1. Ibrahim Fanous
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  2. Patrick Dillon
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Correspondence to Patrick Dillon.

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Fanous, I., Dillon, P. Cancer treatment-related cardiac toxicity: prevention, assessment and management. Med Oncol 33, 84 (2016). https://doi.org/10.1007/s12032-016-0801-5

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