Cardio-Oncology (May 2019)

NT-proBNP correlates with LVEF decline in HER2-positive breast cancer patients treated with trastuzumab

  • Nathalie I. Bouwer,
  • Crista Liesting,
  • Marcel J. M. Kofflard,
  • Sylvia M. Sprangers-van Campen,
  • Jasper J. Brugts,
  • Jos J. E. M. Kitzen,
  • Michael A. Fouraux,
  • Mark-David Levin,
  • Eric Boersma

DOI
https://doi.org/10.1186/s40959-019-0039-4
Journal volume & issue
Vol. 5, no. 1
pp. 1 – 10

Abstract

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Abstract Background Early 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. Methods This 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) 10% since inclusion, and/or the incidence of a clinical cardiac event. Results A 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. Conclusions NT-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.

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