Prediction of trastuzumab-induced cardiotoxicity in breast cancer patients receiving anthracycline-based chemotherapy.

Abstract

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 12months of trastuzumab therapy. Of 61 patients, 18 patients (29.5%) developed trastuzumab-induced cardiomyopathy (CM) at 6 and 9months of therapy (LVEF declines ≥ 10%), GLS and radial strain significantly decreased in CM group at 3months of trastuzumab treatment, the value of GLS at 3months 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.