Left Ventricular Dysfunction in Breast Cancer Patients Receiving Trastuzumab: An Observational Study in a Cohort of Iraqi Breast Cancer Patients
Keywords:
Breast cancer, Ejection fraction, TrastuzumabAbstract
Background : Cardiotoxicity is a well recognized adverse event of trastuzumab. This study was designed to evaluate the frequency of decline in left ventricular ejection fraction (LVEF) to less than 50% in patients with breast cancer who have received trastuzumab in a daily practice setting.
Methods : Retrospective observational study of 116 patients with HER2 positive breast cancer treated with trastuzumab in one center between May 2012 and January 2017.
Results : Left ventricular ejection fraction decline to less than 50% was observed in 7 patients (6%). Patients above 70 years of age have the highest frequency of LVEF decline (33%). All events of LVEF decline was reported in the first six months of treatment. Prolonged administration of trastuzumab beyond one year was not associated with adverse cardiac events. Previous anthracycline exposure and chest irradiation was not found to be associated with LVEF decline.
Conclusions : Events of LVEF decline to less than 50% associated with trastuzumab use seems to be slightly higher in general daily practice than in clinical trial setting, especially in patients above 70 years, calling for better patient selection. First year of trastuzumab therapy carries the highest risk of cardiac events which necessitates a close cardiac monitoring, thereafter, periodic LVEF measurements can be reduced to reduce the costs.
References
Seferina SC, de Boer M, Derksen MW et al. Cardiotoxicity and Cardiac Monitoring During Adjuvant Trastuzumab in Daily Dutch Practice: A Study of the Southeast Netherlands Breast Cancer Consortium. Oncologist 2016 May;21(5):555-62.
Bonifazi M, Franchi M, Rossi M et al. Trastuzumab-related cardiotoxicity in early breast cancer: a cohort study. Oncologist 2013;18(7):795-801
Burstein HJ. The distinctive nature of HER2-positive breast cancers. N Engl J Med 2005;353:1652-1654.
Rossi M, Carioli G, Bonifazi M et al. Trastuzumab for HER2+ metastatic breast cancer in clinical practice: Cardiotoxicity and overall survival. Eur J cancer 2016 Jan;52:41-9.
Chen J, Long JB, Hurria A et al. Incidence of Heart Failure or Cardiomyopathy After Adjuvant Trastuzumab Therapy for Breast Cancer. J Am Coll Cardiol. 2012; 60:2504-2512
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.NEngl JMed2001;344:783–792.
Piccart-Gebhart MJ, Procter M, Leyland-Jones B et al. Trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer. N Engl J Med 2005;
:1659–1672.
Perez EA, Romond EH, Suman VJ et al. Trastuzumab plus adjuvant chemotherapy for human epidermal growth factor receptor 2-positive breast cancer: Planned joint analysis of overall survival from NSABP B-31 and NCCTG N9831. J Clin Oncol 2014;32:3744–3752.
Goldhirsch A, Piccart-Gebhart M, Procter M, et al. HERA TRIAL: 2 years versus 1 year of trastuzumab after adjuvant chemotherapy in women with HER2-positive early breast cancer at 8 years of median follow up. Cancer Research 2012;72:S5-2.
Romond E, Perez E, Bryant J, et al. Trastuzumab plus adjuvant chemotherapy for operable HER2-positive breast cancer. N Engl J Med 2005;353:1673-1684.
Joensuu H, Kellokumpu-Lehtinen P, Bono P, et al. Adjuvant docetaxel or vinorelbine with or without trastuzumab for breast cancer. N Engl J Med 2006;354:809-820.
National Cancer Institute. FDA approval for trastuzumab.Available at http://www.cancer.gov/ about-cancer/treatment/drugs/fda-trastuzumab.
Slamon D, Eiermann W, Robert N, et al. Adjuvant trastuzumab in HER2-positive breast cancer. N Engl J Med 2011;365:1273– 83.
Crone SA, Zhao YY, Fan L et al. ErbB2 is essential in the prevention of dilated cardiomyopathy. Nat Med 2002;8:459–465.
Moja L, Tagliabue L, Balduzzi S et al. Trastuzumab containing regimens for early breast cancer. Cochrane Database Syst Rev 2012 Apr 18;(4):CD006243.
Balduzzi S, Mantarro S, Guarneri V et al. Trastuzumab containing regimens for metastatic breast cancer. Cochrane Database Syst Rev 2014 Jun 12;(6):CD006242..
Serrano C, Cortes J, De Mattos-Arruda L et al. Trastuzumab-related cardiotoxicity in the elderly:A role for cardiovascular risk factors. Ann Oncol 2012;23:897–902.
Ayres LR, de Almeida Campos MS, de Oliveira Gozzo T et al. Trastuzumab induced cardiotoxicity in HER2 positive breast cancer patients attended in a tertiary hospital. Int J Clin Pharm. 2015 Apr;37(2):365-72.
Tarantini L, Gori S, Faggiano P et al. Adjuvant trastuzumab cardiotoxicity in patients over 60 years of age with early breast cancer: A multicenter cohort analysis. Ann Oncol 2012;23:3058 –3063.
Tsai HT, Isaacs C, Fu AZ et al. Risk of cardiovascular adverse events from trastuzumab in elderly persons with breast cancer: a population-based study. Breast Cancer Res Treat. 2014 Feb;144(1):163-70.
Shih V, Chan A, Chiang J et al. Cardiotoxicity risks of adjuvant trastuzumab in Asian breast cancer patients. J Clin Oncol 2009 May 20;27(15_suppl):561.
Hsu-Chih Chien, Yea-Huei Kao Yang, Jane P. F. Ba. Trastuzumab-Related Cardiotoxic Effects in Taiwanese Women. A Nationwide Cohort Study. JAMA Oncol. 2016;2(10):1317-1325.
Withrow D, Verma S, Dent R et al. Trastuzumab-mediated cardiotoxicity in the nontrial setting : Evaluation of patients receiving adjuvant trastuzumab at an academic center. J Clin Oncol. 2009 May 20;27(15_suppl):e11550.
Seidman A, Hudis C, Pierri MK, et al. Cardiac dysfunction in the trastuzumab clinical trials experience. J Clin Oncol 2002; 20:1215–1221.
Guarneri V, Lenihan DJ, Valero V, et al. Long-term cardiac tolerability of trastuzumab in metastatic breast cancer: The M.D. Anderson Cancer Center experience. J Clin Oncol 2006; 24:4107–4115.
Adamo V, Ricciardi GR, Adamo B, et al. The risk of toxicities from trastuzumab, alone or in combination, in an elderly breast cancer population. Oncology 2014; 86:16–21.
Pietras RJ, Poen JC, Gallardo D, Wongvipat PN, Lee HJ, Slamon DJ. Monoclonal antibody to HER-2/neu receptor modulates repair of radiation–induced DNA damage and enhances radiosensitivity of human breast cancer cells overexpressing this oncogene. Cancer Res. 1999;59:1347–55.
Law AB, Evans T, Hayward RL, Higgins GS, Murray KL, Summers D, et al. Possible radiation sensitisation by trastuzumab leading to radiation-induced myelitis. Breast Care (Basel) 2009;4:40–2.
Tan-Chiu E, Yothers G, Romond E, Geyer CE, Jr, Ewer M, Keefe D, et al. Assessement of cardiac dysfunction in a randomized trial comparing doxorubicin and cyclophosphamyde followed by paclitaxel, with or without trastuzumab as adjuvant therapy in node positive, human epidermal growth factor receptor 2-overexpressing breast cancer: NSABP B-31. J Clin Oncol. 2005;23:7811–19.
Halyard MY, Pisansky TM, Dueck AC, Suman V, Pierce L, Solin L, et al. Radiotherapy and adjuvant trastuzumab in operable breast cancer: tolerability and adverse event data from the NCCTG Phase III Trial N9831. J Clin Oncol. 2009;27:2638–44.
Bowles EJ, Wellman R, Feigelson HS, et al. Risk of heart failure in breast cancer patients after anthracycline and trastuzumab treatment: a retrospective cohort study. J Natl Cancer Inst. 2012;104:1293–1305.
Guglin M, Cutro R, Mishkin JD. Trastuzumab induced cardiomyopathy. J Card Fail 2008;14:437–444.
Tarantini L, Cioffi G, Gori S et al. Trastuzumab adjuvant chemotherapy and cardiotoxicity in real world women with breast cancer. J Card Fail 2012;18:113–11
