Advertisement

Tumor Biology

, Volume 37, Issue 3, pp 3379–3387 | Cite as

Serum biomarkers evaluation to predict chemotherapy-induced cardiotoxicity in breast cancer patients

  • Francesca De Iuliis
  • Gerardo Salerno
  • Ludovica Taglieri
  • Luciano De Biase
  • Rosina Lanza
  • Patrizia Cardelli
  • Susanna Scarpa
Original Article

Abstract

Anti-neoplastic chemotherapy can determine various side effects, including cardiotoxicity, and no real guidelines for its early detection and management have been developed. The aim of this study is to find some plasmatic markers able to identify breast cancer patients that are at greater risk of developing cardiovascular complications during chemotherapy, in particular heart failure. A prospective study on 100 breast cancer patients with mean age of 66 years in adjuvant treatment with anthracyclines, taxanes, and trastuzumab was performed. Patients underwent cardiological examination before starting treatment (T0) and at 3 months (T1), 6 months (T2), and 1 year (T3) after treatment. Evaluation of serum cardiac markers and N-terminal pro-brain natriuretic peptide (NT-proBNP) was performed at T0, T1, T2, and T3, simultaneously to electrocardiogram and echocardiogram, showing a significant increase in NT-proBNP concentration (p > 0.0001) at T1, T2, and T3, before left ventricular ejection fraction decrease became evident. Human epidermal growth factor receptor 2 (HER2)-negative patients were more susceptible to mild hematological cardiotoxicity, while HER2-positive patients were more susceptible to severe cardiotoxicity. A significant correlation between NT-proBNP increased values after chemotherapy and prediction of mortality at 1 year was evidenced. From our experience, serum biomarker detection was able to support an early diagnosis of cardiac damage, also in the absence of left ventricular ejection fraction decrease. Therefore, the evaluation of specific plasmatic markers for cardiac damage is more sensitive than echocardiography in the early diagnosis of chemotherapy-related cardiotoxicity; furthermore, it can also add a prognostic value on outcome.

Keywords

Breast cancer Chemotherapy Anthracicline Taxanes Trastuzumab Cardiotoxicity 

Notes

Compliance with ethical standards

Conflicts of interest

None

References

  1. 1.
    Guo S, Wong S. Cardiovascular toxicities from systemic breast cancer therapy. Front Oncol. 2014;4:346. doi: 10.3389/fonc.2014.00346.PubMedPubMedCentralGoogle Scholar
  2. 2.
    Fabian C. Prevention and treatment of cardiac dysfunction in breast cancer survivors. Adv Exp Med Biol. 2015;862:213–30. doi: 10.1007/978-3-319-16366-6-14.CrossRefPubMedGoogle Scholar
  3. 3.
    Albini A, Pennesi G, Donatelli F, Cammarota R, De Flora S, Noonan DM. Cardiotoxicity of anticancer drugs: the need for cardio-oncology and cardio-oncological prevention. J Natl Cancer Inst. 2010;102:14–25. doi: 10.1093/jnci/djp440.CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Bowles EJ, Wellman R, Feigelson HS. Risk of heart failure in breast cancer patients after anthracycline and trastuzumab treatment: a retrospective cohort study. J Natl Cancer Inst. 2012;104:1293–305. doi: 10.1093/jnci/djs317.CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Yu AF, Yadav NU, Lung BY, Eaton AA, Thaler HT, Hudis CA, et al. Trastuzumab interruption and treatment-induced cardiotoxicity in early HER2-positive breast cancer. Breast Cancer Res Treat. 2015;149:489–95. doi: 10.1007/s10549-014-3253-7.CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Rochette L, Guenancia C, Gudjoncik A, Hachet O, Zeller M, Cottin Y, et al. Anthracyclines/trastuzumab: new aspects of cardiotoxicity and molecular mechanisms. Trends Pharmacol Sci. 2015;36:326–48. doi: 10.1016/j.tips.2015.03.005.CrossRefPubMedGoogle Scholar
  7. 7.
    Vulsteke C, Pfeil AM, Maggen C, Schwenkglenks M, Pettengell R, Szucs TD, et al. Clinical and genetic risk factors for epirubicin-induced cardiac toxicity in early breast cancer patients. Breast Cancer Res Treat. 2015;152:67–76. doi: 10.1007/s10549-015-3437-9.CrossRefPubMedGoogle Scholar
  8. 8.
    Swain SM, Whaley FS, Ewer MS. Congestive heart failure in patients treated with doxorubicin: a retrospective analysis of three trials. Cancer. 2003;97:2869–79.CrossRefPubMedGoogle Scholar
  9. 9.
    Jensen BV, Skovsgaard T, Nielsen SL. Functional monitoring of anthracycline cardiotoxicity: a prospective, blinded, long-term observational study of outcome in 120 patients. Ann Oncol. 2002;13:699–709.CrossRefPubMedGoogle Scholar
  10. 10.
    Wang L, Tan TC, Halpern EF, Neilan TG, Francis SA, Picard MH, et al. Major cardiac events and the value of echocardiographic evaluation in patients receiving anthracycline-based chemotherapy. Am J Cardiol. 2015. doi: 10.1016/j.amjcard.2015.04.064.Google Scholar
  11. 11.
    Francis SA, Cheng S, Arteaga CL, Moslehi J. Heart failure and breast cancer therapies: moving towards personalized risk assessment. J Am Heart Assoc. 2014;3:e000780. doi: 10.1161/JAHA.113.000780.CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Villarraga HR, Herrmann J, Nkomo VT. Cardio-oncology: role of echocardiography. Prog Cardiovasc Dis. 2014;57:10–8. doi: 10.1016/j.pcad.2014.05.002.CrossRefPubMedGoogle Scholar
  13. 13.
    Sandoo A, Kitas GD, Carmichael AR. Breast cancer therapy and cardiovascular risk: focus on trastuzumab. Vasc Health Risk Manag. 2015;11:223–8. doi: 10.2147/VHRM.S69641.CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Sawaya H, Sebag IA, Plana JC, Januzzi JL, Ky B, Tan TC, et al. Assessment of echocardiography and biomarkers for the extended prediction of cardiotoxicity in patients treated with anthracyclines, taxanes, and trastuzumab. Circ Cardiovasc Imag. 2012;5:596–603.CrossRefGoogle Scholar
  15. 15.
    Chavez-MacGregor M, Niu J, Zhang N, Elting LS, Smith BD, Banchs J, et al. Cardiac monitoring during adjuvant trastuzumab-based chemotherapy among older patients with breast cancer. J Clin Oncol. 2015;33:2176–83. doi: 10.1200/JCO.2014.58.9465.CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Appel JM, Zerahn B, Møller S, Christensen HM, Søgaard P, Ejlertsen B, et al. Long-term heart function after adjuvant epirubicin chemotherapy for breast cancer. Acta Oncol. 2012;51:1054–61. doi: 10.3109/0284186X.2012.702920.CrossRefPubMedGoogle Scholar
  17. 17.
    van Boxtel W, Bulten BF, Mavinkurve-Groothuis AM, Bellersen L, Mandigers CM, Joosten LA, et al. New biomarkers for early detection of cardiotoxicity after treatment with docetaxel, doxorubicin and cyclophosphamide. Biomarkers. 2015;20:143–8. doi: 10.3109/1354750X.2015.1040839.CrossRefPubMedGoogle Scholar
  18. 18.
    Lenihan DJ. Cardiac biomarkers, cardiotoxicity, and active collaboration: is this the final frontier or the wave we should catch? J Am Coll Cardiol. 2014;63:817–8. doi: 10.1016/j.jacc.2013.10.060.CrossRefPubMedGoogle Scholar
  19. 19.
    Morris PG, Chen C, Steingart R, Fleisher M, Lin N, Moy B, et al. Troponin I and C-reactive protein are commonly detected in patients with breast cancer treated with dose-dense chemotherapy incorporating trastuzumab and lapatinib. Clin Cancer Res. 2011;17:3490–9. doi: 10.1158/1078-0432.CCR-10-1359.CrossRefPubMedGoogle Scholar
  20. 20.
    Mokuyasu S, Suzuki Y, Kawahara E, Seto T, Tokuda Y (2014) High-sensitivity cardiac troponin I detection for 2 types of drug-induced cardiotoxicity in patients with breast cancer. Breast Cancer 2014 Feb 23Google Scholar
  21. 21.
    Katsurada K, Ichida M, Sakuragi M, Takehara M, Hozumi Y, Kario K. High-sensitivity troponin T as a marker to predict cardiotoxicity in breast cancer patients with adjuvant trastuzumab therapy. Springerplus. 2014;3:620. doi: 10.1186/2193-1801-3-620.
  22. 22.
    Ky B, French B, Levy WC, Sweitzer NK, Fang JC, Wu AH, et al. Multiple biomarkers for risk prediction in chronic heart failure. Circ Heart Fail. 2012;5:183–90. doi: 10.1161/CIRCHEARTFAILURE.111.965020.CrossRefPubMedPubMedCentralGoogle Scholar
  23. 23.
    Ky B, Putt M, Sawaya H, French B, Januzzi Jr JL, Sebag IA, et al. Early increases in multiple biomarkers predict subsequent cardiotoxicity in patients with breast cancer treated with doxorubicin, taxanes, and trastuzumab. J Am Coll Cardiol. 2012;63:809–16. doi: 10.1016/j.jacc.2013.10.061.CrossRefGoogle Scholar
  24. 24.
    Tian S, Hirshfield KM, Jabbour SK, Toppmeyer D, Haffty BG, Khan AJ, et al. Serum biomarkers for the detection of cardiac toxicity after chemotherapy and radiation therapy in breast cancer patients. Front Oncol. 2014;4:277. doi: 10.3389/fonc.2014.00277.CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Komiya K, Ishii H, Murakami J, Yamamoto H, Okada F, Satoh K, et al. Relationship between CT findings and the plasma levels of brain natriuretic peptide in 29 patients with acute cardiogenic pulmonary edema. Acad Radiol. 2012;19:851–6. doi: 10.1016/j.acra.2012.03.014.CrossRefPubMedGoogle Scholar
  26. 26.
    Ürun Y, Utkan G, Yalcin B, Akbulut H, Onur H, Oztuna DG, et al. The role of cardiac biomarkers as predictors of trastuzumab cardiotoxicity in patients with breast cancer. Exp Oncol. 2015;37:53–7.PubMedGoogle Scholar
  27. 27.
    Motiwala SR, Szymonifka J, Belcher A, Weiner RB, Baggish AL, Gaggin HK, et al. Measurement of novel biomarkers to predict chronic heart failure outcomes and left ventricular remodeling. J Cardiovasc Transl Res. 2014;7:250–61. doi: 10.1007/s12265-013-9522-8.CrossRefPubMedGoogle Scholar
  28. 28.
    Fiúza M. Cardiotoxicity associated with trastuzumab treatment of HER2+ breast cancer. Adv Ther. 2009;26:9–17. doi: 10.1007/s12325-009-0048-z.CrossRefGoogle Scholar
  29. 29.
    Vasile VC, Saenger AK, Kroning JM, Klee GG, Jaffe AS. Biologic variation of a novel cardiac troponin I assay. Clin Chem. 2011;57:1080–1. doi: 10.1373/clinchem.2011.162545.CrossRefPubMedGoogle Scholar
  30. 30.
    Cardinale D, Colombo A, Torrisi R, Sandri MT, Civelli M, Salvatici M, et al. Trastuzumab-induced cardiotoxicity: clinical and prognostic implications of troponin I evaluation. J Clin Oncol. 2010;28:3910–6. doi: 10.1200/JCO.2009.27.3615.CrossRefPubMedGoogle Scholar
  31. 31.
    Cil T, Kaplan AM, Altintas A, Akin AM, Alan S, Isikdogan A. Use of N-terminal pro-brain natriuretic peptide to assess left ventricular function after adjuvant doxorubicin therapy in early breast cancer patients: a prospective series. Clin Drug Investig. 2009;29:131–7. doi: 10.2165/0044011-200929020-00007.CrossRefPubMedGoogle Scholar
  32. 32.
    Kittiwarawut A, Vorasettakarnkij Y, Tanasanvimon S, Manasnayakorn S, Sriuranpong V. Serum NT-proBNP in the early detection of doxorubicin-induced cardiac dysfunction. Asia Pac J Clin Oncol. 2013;9:155–61. doi: 10.1111/j.1743-7563.2012.01588.x.CrossRefPubMedGoogle Scholar
  33. 33.
    Ky B, Putt M, Sawaya H, French B, Januzzi Jr JL, Sebag IA, et al. Early increases in multiple biomarkers predict subsequent cardiotoxicity in patients with breast cancer treated with Doxorubicin, taxanes, and trastuzumab. J Am Coll Cardiol. 2014;63:809–16. doi: 10.1016/j.jacc.2013.10.061.CrossRefPubMedGoogle Scholar
  34. 34.
    Meacham LR, Chow EJ, Ness KK, Kamdar KY, Chen Y, Yasui Y, et al. Cardiovascular risk factors in adult survivors of pediatric cancer—a report from the childhood cancer survivor study. Cancer Epidemiol Biomarkers Prev. 2010;19:170–81. doi: 10.1158/1055-9965.EPI-09-0555.CrossRefPubMedPubMedCentralGoogle Scholar
  35. 35.
    Ewer MS, Ewer SM. Cardiotoxicity of anticancer treatments. Nat Rev Cardiol. 2015. doi: 10.1038/nrcardio.2015.65.Google Scholar
  36. 36.
    Shelburne N, Adhikari B, Brell J, Davis M, Desvigne-Nickens P, Freedman A, Minasian L, Force T, Remick SC (2014) Cancer treatment-related cardiotoxicity: current state of knowledge and future research priorities. J Natl Cancer Inst 106. doi:  10.1093/jnci/dju232
  37. 37.
    Stevens PL, Lenihan DJ. Cardiotoxicity due to chemotherapy: the role of biomarkers. Curr Cardiol Rep. 2015;17:603. doi: 10.1007/s11886-015-0603-y.CrossRefPubMedGoogle Scholar
  38. 38.
    Singh D, Thakur A, Tang WH. Utilizing cardiac biomarkers to detect and prevent chemotherapy-induced cardiomyopathy. Curr Heart Fail Rep. 2015;12:255–62. doi: 10.1007/s11897-015-0258-4.CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2015

Authors and Affiliations

  • Francesca De Iuliis
    • 1
  • Gerardo Salerno
    • 2
  • Ludovica Taglieri
    • 1
  • Luciano De Biase
    • 3
  • Rosina Lanza
    • 4
  • Patrizia Cardelli
    • 2
  • Susanna Scarpa
    • 1
  1. 1.Experimental Medicine DepartmentUniversity of Rome SapienzaRomeItaly
  2. 2.Laboratory of Diagnostics, Department of Clinical and Molecular MedicineUniversity of Rome SapienzaRomeItaly
  3. 3.Cardiology Center, Department of Clinical and Molecular MedicineUniversity of Rome SapienzaRomeItaly
  4. 4.Ginecology, Obstetrics and Urology DepartmentUniversity of Rome SapienzaRomeItaly

Personalised recommendations