Prediction of trastuzumab-induced cardiotoxicity in breast cancer patients receiving anthracycline-based chemotherapy
- 124 Downloads
Adjuvant trastuzumab improved overall survival and reduced the risk for disease recurrence in women with breast cancers, because of its potential cardiotoxicity, careful monitoring of left ventricular (LV) function during treatment is required.
This study investigates, whether myocardial strain imaging and level of N-terminal pro-brain natriuretic peptide (NT-pro BNP) could predict subsequent reduction in LVEF in breast cancer patients received adjuvant trastuzumab. 61 women with pathologically proven breast cancer HER-2 positive received AC (Doxorubicin–Cyclophosphamide) for 4 cycles, followed by paclitaxel with Trastuzumab were enrolled. Clinical, conventional echocardiographic parameters, myocardial strain imaging [global longitudinal peak systolic strain (GLS), radial and circumferential systolic strain] and level of NT pro-BNP were measured at baseline, after 3, 6, 9 and 12 months of trastuzumab therapy.
Of 61 patients, 18 patients (29.5%) developed trastuzumab-induced cardiomyopathy (CM) at 6 and 9 months of therapy (LVEF declines ≥ 10%), GLS and radial strain significantly decreased in CM group at 3 months of trastuzumab treatment, the value of GLS at 3 months was the strongest predictors of cardiotoxicity its area under the curve (AUC 0.98) with an optimal cut-off for GLS (− 18%) having 92.5% sensitivity and 83% specificity. NT-pro BNP levels were not predictive of later trastuzumab-induced cardiac dysfunction.
Myocardial strain imaging has been able to predict pre-clinical changes in LV systolic function and GLS is an independent early predictor of subsequent reduction in EF in breast cancer patients treated with trastuzumab.
KeywordsBreast cancer Trastuzumab Cardiotoxicity Myocardial strain
This study was not funded.
Compliance with ethical standards
Conflict of interest
Wafaa S. El-Sherbeny, Nesreen M. Sabry and Radwa M. Sharbay declare that they have no conflict of interest.
This study was approved by the Ethics Committee in the Faculty of Medicine, Tanta University and with Helsinki Declaration of 1964 and later revision.
Informed consent was obtained from all patients included in the study.
- 13.Teske AJ, De Boeek BW, Melman PG, et al. Echocardiographic quantification of myocardial function using tissue deformation imaging, a guide to image accession and analysis using tissue Doppler and speckle tracking. Ultrasound. 2007;5:27.Google Scholar
- 16.Tan-Chiu E, Yothers G, Romond E, et al. Assessment of cardiac dysfunction in a randomized trial comparing doxorubicin and cyclophosphamide 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(31):7811–9.CrossRefPubMedGoogle Scholar
- 17.Perez EA, Suman VJ, Davidson NE, et al. Cardiac safety analysis of doxorubicin and cyclophosphamide followed by paclitaxel with or without trastuzumab in the North Central Cancer Treatment Group N9831 adjuvant breast cancer trial. J Clin Oncol. 2008;26(8):1231–8.CrossRefPubMedPubMedCentralGoogle Scholar
- 21.Romond EH, Jeong JH, Rastogi P, et al. Seven-year segment assessment of cardiac function in NSABP B-31, a randomized trial comparing doxorubicin and cyclophosphamide followed by paclitaxel (ACP) with ACP plus trastuzumab as adjuvant therapy for patients with node-positive, human epidermal growth factor receptor 2-positive breast cancer. J Clin Oncol. 2012;30(31):3792.CrossRefPubMedPubMedCentralGoogle Scholar
- 22.Tan-Chiu E, Yothers G, Romond E, et al. Assessment of cardiac dysfunction in a randomized trial comparing doxorubicin and cyclophosphamide 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(31):7811–9.CrossRefPubMedGoogle Scholar
- 31.Fallah-Rad N, Walker JR, Wassef A, 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.CrossRefPubMedGoogle Scholar