Delta NT-proBNP predicts cardiotoxicity in HER2-positive breast cancer patients treated with trastuzumab

Abstract

Background Overall survival has improved significantly in patients with human epidermal growth receptor 2 (HER2)-positive breast cancer due to the use of the monoclonal antibody trastuzumab blocking HER2. However, patients may develop trastuzumab-induced cardiotoxicity (TIC) leading to congestive heart failure. Here we assessed whether analysing NT-proBNP and assessment of electrocardiography (ECG) could detect TIC during trastuzumab therapy. Methods One hundred thirty-six patients undergoing adjuvant, neoadjuvant or palliative chemotherapy and HER2 blockade for HER2-positive breast cancer were prospectively assessed with echocardiography, ECG and N-terminal – pro hormone B-type natriuretic peptide (NT-proBNP) testing at baseline and at 6 and 12 months of trastuzumab therapy. TIC was defined as a left ventricular ejection fraction (LVEF) of less than 50% and a decline from baseline of ≥10 units. Results Six patients developed TIC under 12 months of trastuzumab therapy (incidence 4.4%). NT-proBNP increased from 198.8 ± 64.0 pg/ml to 678.7 ± 132.4 pg/ml (p < .05) in TIC patients. With a cut-off point of 276.5 pg/ml for NTproBNP and increase in NT-proBNP by 75.8 pg/ml from baseline the sensitivity was 100% and the specificity 95% to detect TIC. Compared with controls, TIC patients were older (68.3 ± 1.1 years and 56.2 ± 1.4 years, respectively; p < .01), had more often diabetes mellitus (OR = 63.5, 95% CI: 5.63–915, p < .01) and atrial fibrillation (OR = 12.3; 95% CI: 1.89–74.62; p < .05) and had lower baseline LVEF (57.1 ± 1.4% and 61.4 ± 0.3%, respectively; p < .001). Abnormal ECGs were common in patients developing TIC. Conclusions Measuring changes in NTproBNP may be used to monitor patients for TIC under trastuzumab therapy. Patients with a cardiovascular risk profile are more at risk of developing TIC.