Abstract
BackgroundEarly identification of cardiac dysfunction by non-invasive imaging in HER2-positive breast cancer patients treated with trastuzumab is challenging. In particular multigated acquisition (MUGA) scan, which is most widely used, is unable to detect subclinical cardiac changes. The use of N-terminal pro-brain natriuretic peptide (NT-proBNP), a serum biomarker of myocardial stress, might improve timely diagnosis.MethodsThis prospective, single-center, cohort study included patients with HER2-positive breast cancer who started trastuzumab therapy. Echocardiography was scheduled at regular intervals every 3 months during one year follow-up for cardiac function monitoring. For research purposes, NT-proBNP was determined at the same time points. Trastuzumab-induced cardiotoxicity (TIC) was the primary study endpoint, defined as a left ventricular ejection fraction (LVEF) < 45%, and/or an absolute decline in LVEF > 10% since inclusion, and/or the incidence of a clinical cardiac event.ResultsA total of 135 patients were enrolled between April 2008 and June 2016, with a median age of 54 years (IQR: 47–61). By three-dimensional echocardiography (3DE), the median LVEF at baseline was 62% (IQR: 58–65). At a median of 6 months (IQR: 5–11), 45 patients (33%) reached the study endpoint of TIC. Patients with TIC had a mean change of − 9.5% in LVEF (95% CI -7.2 to − 11.7; p = 0.001) during 1 year of trastuzumab treatment. Both NT-proBNP at baseline (HR 1.04, 95% CI 1.02–1.07; p = 0.003) and LVEF decline during anthracycline treatment prior to the start of trastuzumab (HR 1.16, 95% CI 1.07–1.25; p < 0.001) were independently associated with development of TIC. The level of NT-proBNP during follow-up was associated too with development of TIC (HR 1.06 per 10 pmol/l difference, 95% CI 1.02–1.10; p = 0.008). No steadily or sudden increase in NT-proBNP prior to TIC was observed.ConclusionsNT-proBNP cannot be used as a surrogate monitoring tool for trastuzumab-induced cardiotoxicity in HER2-positive breast cancer patients during the first year of treatment. Patients showing an LVEF decline during anthracycline pre-treatment appeared vulnerable for trastuzumab-induced cardiotoxicity.
Highlights
The identification of cardiac dysfunction in Human Epidermal growth Receptor 2 (HER2) positive breast cancer patients treated with trastuzumab is challenging, but crucial in order to prevent the development of heart failure in these patients
We aimed to assess the potency of a screening-strategy utilizing repeatedly measured NT-proBNP levels to detect trastuzumab-induced cardiotoxicity measured with three-dimensional echocardiography (3DE) in a representative cohort of HER2-positive breast cancer patients
A total of 15 patients were excluded from the analyses because they did not receive trastuzumab treatment (N = 4), had no echocardiography (N = 8) or NT-proBNP measurement (N = 3)
Summary
The identification of cardiac dysfunction in Human Epidermal growth Receptor 2 (HER2) positive breast cancer patients treated with trastuzumab is challenging, but crucial in order to prevent the development of heart failure in these patients. It is essential to identify early subclinical cardiac dysfunction in breast cancer patients treated with trastuzumab. [4] Multigated acquisition (MUGA) scans are widely used to monitor cardiac function in this patient population, but identification of cardiotoxicity by this technique is challenging. MUGA scans provide LVEF assessments with high inter- and intra-observer variability [5], and fail to detect early subclinical cardiac alterations, because of initial compensatory mechanisms of the left ventricle to prevent functional cardiac impairment. Identification of cardiac dysfunction by non-invasive imaging in HER2-positive breast cancer patients treated with trastuzumab is challenging. The use of N-terminal pro-brain natriuretic peptide (NTproBNP), a serum biomarker of myocardial stress, might improve timely diagnosis
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