Are Biomarkers Predictive of Anthracycline-Induced Cardiac Dysfunction?

  • Malik, Abhidha (Department of Radiation Oncology, Dr B.R.A Institute of Rotary Cancer Hospital, All India Institute of Medical Sciences) ;
  • Jeyaraj, Pamela Alice (Department of Radiation Oncology, Christian Medical College and Hospital) ;
  • Calton, Rajneesh (Department of Cardiology, Christian Medical College and Hospital) ;
  • Uppal, Bharti (Department of Biochemistry, Christian Medical College and Hospital) ;
  • Negi, Preety (Department of Radiation Oncology, Christian Medical College and Hospital) ;
  • Shankar, Abhishek (Department of Radiation Oncology, Dr B.R.A Institute of Rotary Cancer Hospital, All India Institute of Medical Sciences) ;
  • Patil, Jaineet (Department of Radiation Oncology, Christian Medical College and Hospital) ;
  • Mahajan, Manmohan Kishan (Department of Radiation Oncology, Christian Medical College and Hospital)
  • Published : 2016.06.01


Background: The early detection of anthracycline- induced cardiotoxicity is very important since it might be useful in prevention of cardiac decompensation. This study was designed with the intent of assessing the usefulness of cardiac troponin T (cTnT) and NT- Pro BNP estimation in early prediction of anthracycline induced cardiotoxicity. Materials and Methods: In this prospective study histologically proven breast cancer patients who were scheduled to receive anthracycline containing combination chemotherapy as a part of multimodality treatment were enrolled. Baseline cardiac evaluation was performed by echocardiography (ECHO) and biomarkers like cardiac troponin T (cTnT) and N terminal- pro brain natriuretic peptide (NT- Pro BNP). All patients underwent cTnT and NT- Pro BNP estimation within 24 hours of each cycle of chemotherapy and were followed up after 6 months of initiation of chemotherapy. Any changes in follow up ECHO were compared to ECHO at baseline and cTnT and NT- Pro BNP levels after each cycle of anthracycline-based chemotherapy. Results: Initial data were obtained for 33 patients. Mean change in left ventricular diastolic diameter (LVDD) within 6 months was $0.154{\pm}0.433cms$ (p value=0.049). Seven out of 33 patients had an increase in biomarker cTnT levels (p value=0.5). A significant change in baseline and follow up LVDD was observed in patients with raised cTnT levels (p value=0.026) whereas no change was seen in ejection fraction (EF) and left atrial diameters (LAD) within 6 months of chemotherapy. NT- Pro BNP levels increased in significant number of patients (p value ${\leq}0.0001$) but no statistically significant change was observed in the ECHO parameters within 6 months. Conclusions: Functional monitoring is a poorly effective method in early estimation of anthracycline induced cardiac dysfunction. Estimation of biomarkers after chemotherapy may allow stratification of patients in various risk groups, thereby opening window for interventional strategies in order to prevent permanent damage to the myocardium.


  1. Adamcova M, Sterba M, Simunek T et al (2005). Troponin as a marker of myocardiac damage in drug induced cardiotoxicity. Expert opin Drug Saf, 4, 37-46.
  2. Appel JM, Nielsen D, Zerahn B et al (2007). Anthracyclineinduced chronic cardiotoxicity and heart failure. Acta Oncologica, 46, 576-80.
  3. Billingham ME, Masek MA (1993). The pathology of anthracycline cardiotoxicity in children, adolescents and adults. In: Bricker JT, Green DM, D'Angio G (eds) Cardiac toxicity after treatment for childhood cancer. Wiley-Liss, New York; 17-24.
  4. Broeyer FJF, Osanto S, Ritsema vaneck HJ et al (2008). Evaluation of biomarkers for cardiotoxicity of anthracycline based chemotherapy. J Cancer Res Clin Oncol, 134, 961-68.
  5. Cardinale D, Sandri MT, Colombo A et al (2004). Prognostic value of troponin I in cardiac risk stratification of cancer patients undergoing high-dose chemotherapy. Circulation, 109, 2749-54.
  6. Cardinale D, Sandri MT, Martinoni A et al (2002). Myocardial injury revealed by plasma troponin I in breast cancer treated with high-dose chemotherapy. Ann Oncol, 13, 710-15.
  7. Chia S, Bryce C, Gelmon K. Early Breast Cancer Trialist’s Collaborative group (EBCTCG) (2005). Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15 year survival: an overview of the randomized trials. Lancet, 365, 1687-1717.
  8. Elliott P (2006). Pathogenesis of cardiotoxicity induced by anthracyclines. Semin Oncol, 33, 2-7.
  9. Ewer MS, Martin FJ, Henderson IC et al (2004). Cardiac safety of liposomal anthracyclines. Semin Oncol, 31, 161-81.
  10. Frishman WH, Sung HM, Yee HC et al (1997). Cardiovascular toxicity with cancer chemotherapy. Curr Probl Cancer, 21, 301-60.
  11. Katus HA, Remppis A, Neumann FJ et al (1991). Diagnostic efficiency of troponin T measurement in acute myocardial infarction. Circulation, 83, 1360-67.
  12. Kilickap S, Barista I, Akgul E et al (2005). cTnT can be a useful marker for early detection of anthracycline toxicity. Ann Oncol, 16, 798-804.
  13. Nistico C, Bria E, Cuppone F et al (2007). Troponin-T and myoglobin plus echocardiographic evaluation for monitoring early cardiotoxicity of weekly epirubicin-paclitaxel in metastatic breast cancer patients. Anticancer Drugs, 18, 227-32.
  14. Nysom K, Holm K, Lipsitz SR et al (1998). Relationship between cumulative anthracycline dose and late cardiotoxicity in childhood acute lymphoblastic leukemia. J Clin Oncol, 16, 545-50.
  15. Ryberg M, Nielsen D, Skovsgaard T et al (1998). Epirubicin cardiotoxicity: an analysis of 469 patients with metastatic breast cancer. J Clin Oncol, 16, 3502-08.
  16. Sandri MT, Salvatici M, Cardinale D et al (2005). N-terminal pro B- type natriuretic peptide after high dose chemotherapy; marker predictive of cardiac dysfunction? Clin Chem, 51, 1405-10.
  17. Sawaya H, Sebag IA, Plana JC, et al (2012). Assessment of Echocardiography and Biomarkers for the Extended Prediction of Cardiotoxicity in Patients Treated With Anthracyclines, Taxanes, and Trastuzumab. Circ Cardiovasc Imag, 5, 596-603.
  18. Saxena S, Rekhi B, Bansal A, et al (2005). Clinico-morphological patterns of breast cancer including family history in a New Delhi hospital, India- A cross-sectional study. World J Surg Oncol, 3, 67.
  19. Steven ME and Michael SE (2009). Anthracycline cardiotoxicity: Why are we still interested? Oncol, 23, 3.
  20. Suter TM and Meier B (2002). Detection of anthracyclineinduced cardiotoxicity: is there light at the end of the tunnel? Ann Oncol, 13, 647-9.
  21. Tsutamoto T, Wada A, Maeda K, et al (1999). Plasma brain natriuretic peptide level as a biochemical marker of morbidity and mortality in patients with asymptomatic or minimal symptomatic left ventricular dysfunction. E Heart J, 20, 1799-80.
  22. Von Hoff DD, Layard MW, Basa P et al (1979). Risk factors for doxorubicin-induced congestive heart failure. Ann Intern Med, 91, 710-7
  23. Willial FA, Ruth MP, Grace MD et al (2006). Cancer Epidemiology. Biomarkers and Prevent, 15, 1899-905.
  24. Yancik R, Wesley MN, Ries LA et al (2001). Effect of age and comorbidity in postmenopausal breast cancer patients aged 55 years and older. JAMA, 285, 885-92.
  25. Yau TK (2005). Cardiotoxicity after adjuvant anthracyclinebased chemotherapy and radiotherapy for breast cancer. J HK Coll Radiol, 8, 26-9.

Cited by

  1. Glutathione transferases: substrates, inihibitors and pro-drugs in cancer and neurodegenerative diseases vol.7, pp.1, 2018,