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:10.1186/s40959-019-0039-4

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

Cardiooncology. 2019 May 28:5:4. doi: 10.1186/s40959-019-0039-4. eCollection 2019.

Authors

Nathalie I Bouwer^{1

2}, Crista Liesting², Marcel J M Kofflard², Sylvia M Sprangers-van Campen¹, Jasper J Brugts³, Jos J E M Kitzen¹, Michael A Fouraux⁴, Mark-David Levin¹, Eric Boersma³

Affiliations

¹ 1Department of Internal Medicine, Albert Schweitzer Hospital, 3300 AK, Dordrecht, South-Holland The Netherlands.
² 2Department of Cardiology, Albert Schweitzer Hospital, 3300 AK, Dordrecht, South-Holland The Netherlands.
³ 3Department of Cardiology, Erasmus MC, University Medical Center Rotterdam, 3000 CA, Rotterdam, South-Holland The Netherlands.
⁴ 4Result Laboratorium C.V, Albert Schweitzer Hospital, 3300 AK, Dordrecht, South-Holland The Netherlands.

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) < 45%, and/or an absolute decline in 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.

Keywords: Cardiotoxicity; HER2-positive breast cancer; LVEF decline; NT-proBNP; Trastuzumab.