Advertisement

Medical Oncology

, 34:199 | Cite as

Factors for time to trastuzumab-induced cardiotoxicity in breast cancer patients

  • Mi Hyung Lee
  • Jeong Yee
  • Young Ju Kim
  • Jin Young Moon
  • Joo Hee Kim
  • Sandy Jeong Rhie
  • Hye Sun GwakEmail author
Original Paper

Abstract

Trastuzumab is a drug used for the treatment of metastatic breast cancer patients. Due to blockage of the human epidermal growth factor receptor 2 signaling in cardiac myocytes, cardiotoxicity has been observed. There are many studies that investigated risk factors for trastuzumab-induced cardiotoxicity, but no study has been published for factors on the time to cardiotoxicity. This study aimed to investigate the factors for the time to occur trastuzumab-induced cardiotoxicity. From January 2014 to December 2015, a retrospective study was performed with breast cancer patients who were treated with trastuzumab. Associations between presence of and time to cardiotoxicity and various factors were analyzed. Based on multivariate models, it was found that baseline left ventricular ejection fraction (LVEF) < 62.5% (AHR 5.96, 95% CI 2543–13.95) and anthracycline-based chemotherapy (AHR 7.90, 95% CI 1.05–59.71) were significant factors for time to cardiotoxicity after adjusting other confounding factors. Multivariate analysis also showed that BMI ≥ 23 kg/m2 and baseline LVEF value < 62.5% increased cardiotoxicity 3.0 and 6.6 times, respectively. Our study showed that BMI ≥ 23 kg/m2, LVEF < 62.5%, and anthracycline-based chemotherapy were associated with time to trastuzumab-induced cardiotoxicity. Thus, close monitoring of cardiac function is recommended especially for patients using the above risk factors.

Keywords

Trastuzumab Breast cancer Time to cardiotoxicity Left ventricular ejection fraction 

Notes

Compliance with ethical standards

Conflict of interest

All the authors declare that they have no conflict of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.

Informed consent

The National Cancer Center Institutional Review Board approved this study and waived the requirement for informed consent due to the retrospective nature of the study with collection of anonymous subject data (IRB # NCC2017-0093).

References

  1. 1.
    Romond EH, Perez EA, Bryant J, et al. Trastuzumab plus adjuvant chemotherapy for operable HER2-positive breast cancer. N Engl J Med. 2005;353(16):1673–84.CrossRefPubMedGoogle Scholar
  2. 2.
    Slamon DJ, Clark GM, Wong SG, et al. Human breast cancer: correlation of relapse and survival with amplification of the HER-2/neu oncogened. Science. 1987;235:177–82.CrossRefPubMedGoogle Scholar
  3. 3.
    Hudis CA. Trastuzumab-mechanism of action and use in clinical practice. N Engl J Med. 2007;357:39–51.CrossRefPubMedGoogle Scholar
  4. 4.
    Valabrega G, Montemurro F, Aglietta M. Trastuzumab: mechanism of action, resistance and future perspectives in HER2-overexpressing breast cancer. Ann Oncol. 2007;18:977–84.CrossRefPubMedGoogle Scholar
  5. 5.
    Seidman A, Hudis C, Pierri MK. Cardiac dysfunction in the trastuzumab clinical trials experience. J Clin Oncol. 2002;20:1215–21.CrossRefPubMedGoogle Scholar
  6. 6.
    Slamon DJ, Leyland-Jones B, Shak S, et al. Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2. N Engl J Med. 2001;344:783–92.CrossRefPubMedGoogle Scholar
  7. 7.
    Onitilo AA, Engel JM, Stankowski RV. Cardiovascular toxicity associated with adjuvant trastuzumab therapy: prevalence, patient characteristics, and risk factors. Ther Adv Drug Saf. 2014;5:154–66.CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Belkacémi Y, Gligorov J, Ozsahin M, et al. Concurrent trastuzumab with adjuvant radiotherapy in HER2-positive breast cancer patients: acute toxicity analyses from the French multicentric study. Ann Oncol. 2008;19:1110–6.CrossRefPubMedGoogle Scholar
  9. 9.
    Guenancia C, Lefebvre A, Cardinale D, et al. Obesity as a risk factor for anthracyclines and trastuzumab cardiotoxicity in breast cancer: a systematic review and meta-analysis. J Clin Oncol. 2016;34:3157–65.CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Hamirani Y, Fanous I, Kramer CM, et al. Anthracycline- and trastuzumab-induced cardiotoxicity: a retrospective study. Med Oncol. 2016;33:82.CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Cameron D, Piccart-Gebhart MJ, Gelber RD, et al. 11 years’ follow-up of trastuzumab after adjuvant chemotherapy in HER2-positive early breast cancer: final analysis of the HERceptin Adjuvant (HERA) trial. Lancet. 2017;389:1195–205.CrossRefPubMedGoogle Scholar
  12. 12.
    Guglin M, Hartlage G, Reynolds C, et al. Trastuzumab-induced cardiomyopathy: not as benign as it looks? A retrospective study. J Card Fail. 2009;15:651–7.CrossRefPubMedGoogle Scholar
  13. 13.
    Jawa Z, Perez RM, Garlie L, et al. Risk factors of trastuzumab-induced cardiotoxicity in breast cancer: a meta-analysis. Medicine. 2016;95:e5195.CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Pan WH, Yeh WT. How to define obesity? Evidence-based multiple action points for public awareness, screening, and treatment: an extension of Asian-Pacific recommendations. Asia Pac J Clin Nutr. 2008;17:370–4.PubMedGoogle Scholar
  15. 15.
    Kenchaiah S, Evans JC, Levy D, et al. Obesity and the risk of heart failure. N Engl J Med. 2002;347:305–13.CrossRefPubMedGoogle Scholar
  16. 16.
    Tangiisuran B, Scutt G, Stevenson J, et al. Development and validation of a risk model for predicting adverse drug reactions in older people during hospital stay: Brighton Adverse Drug Reactions Risk (BADRI) model. PLoS ONE. 2014;9:e111254.CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Ewer MS, Lippman SM. Type II chemotherapy-related cardiac dysfunction: time to recognize a new entity. J Clin Oncol. 2005;23:2900–2.CrossRefPubMedGoogle Scholar
  18. 18.
    Crone SA, Zhao YY, Fan L, et al. ErbB2 is essential in the prevention of dilated cardiomyopathy. Nat Med. 2002;8:459–65.CrossRefPubMedGoogle Scholar
  19. 19.
    Gordon LI, Burke MA, Singh AT, et al. Blockade of the erbB2 receptor induces cardiomyocyte death through mitochondrial and reactive oxygen species-dependent pathways. J Biol Chem. 2009;284:2080–7.CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Farolfi A, Melegari E, Aquilina M, et al. Trastuzumab-induced cardiotoxicity in early breast cancer patients: a retrospective study of possible risk and protective factors. Heart. 2013;99:634–9.CrossRefPubMedGoogle Scholar
  21. 21.
    Zeglinski M, Ludke A, Jassal DS, et al. Trastuzumab-induced cardiac dysfunction: a ‘dual-hit’. Exp Clin Cardiol. 2011;16:70–4.PubMedPubMedCentralGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2017

Authors and Affiliations

  1. 1.Graduate School of Converging Clinical & Public HealthEwha Womans UniversitySeoulKorea
  2. 2.Department of PharmacyNational Cancer CenterGoyang-siKorea
  3. 3.Division of Life and Pharmaceutical Sciences, College of PharmacyEwha Womans UniversitySeoulKorea
  4. 4.Institute of Pharmaceutical Science and Technology, College of PharmacyAjou UniversitySuwon-siKorea

Personalised recommendations