Assessment of echocardiography and biomarkers for the extended prediction of cardiotoxicity in patients treated with anthracyclines, taxanes, and trastuzumab

Abstract

Background: Because cancer patients survive longer, the impact of cardiotoxicity associated with the use of cancer treatments escalates. The present study investigates whether early alterations of myocardial strain and blood biomarkers predict incident cardiotoxicity in patients with breast cancer during treatment with anthracyclines, taxanes, and trastuzumab.

Methods and results: Eighty-one women with newly diagnosed human epidermal growth factor receptor 2-positive breast cancer, treated with anthracyclines followed by taxanes and trastuzumab were enrolled to be evaluated every 3 months during their cancer therapy (total of 15 months) using echocardiograms and blood samples. Left ventricular ejection fraction, peak systolic longitudinal, radial, and circumferential myocardial strain were calculated. Ultrasensitive troponin I, N-terminal pro-B-type natriuretic peptide, and the interleukin family member (ST2) were also measured. Left ventricular ejection fraction decreased (64 ± 5% to 59 ± 6%; P<0.0001) over 15 months. Twenty-six patients (32%, [22%-43%]) developed cardiotoxicity as defined by the Cardiac Review and Evaluation Committee Reviewing Trastuzumab; of these patients, 5 (6%, [2%-14%]) had symptoms of heart failure. Peak systolic longitudinal myocardial strain and ultrasensitive troponin I measured at the completion of anthracyclines treatment predicted the subsequent development of cardiotoxicity; no significant associations were observed for left ventricular ejection fraction, N-terminal pro-B-type natriuretic peptide, and ST2. Longitudinal strain was <19% in all patients who later developed heart failure.

Conclusions: In patients with breast cancer treated with anthracyclines, taxanes, and trastuzumab, systolic longitudinal myocardial strain and ultrasensitive troponin I measured at the completion of anthracyclines therapy are useful in the prediction of subsequent cardiotoxicity and may help guide treatment to avoid cardiac side-effects.

Figures

Figure 1

Time course of the study protocol. Mo indicates months.

Figure 2

Consort diagram of the study protocol. LVEF indicates left ventricular ejection fraction; HER2, human epidermal growth factor receptor 2.

Figure 3

Time course of the left ventricular ejection fraction (LVEF; top), the longitudinal strain (middle), and the ultrasensitive (US) troponin (bottom) in 69 patients with breast cancer treated by anthracyclines followed by taxanes and trastuzumab. *P<0.0001 vs before treatment.

Figure 4

Individual time course of left ventricular ejection fraction (LVEF) in 26 patients diagnosed with cardiotoxicity.

Figure 5

Receiver operating characteristic curve for peak systolic longitudinal myocardial strain measured at the completion of the anthracyclines treatment in the prediction of cardiotoxicity.