Assessment of markers of cardiac toxicity following combined treatment of cardiomyocytes with epirubicin and trastuzumab

Claire Tonry, Eimear Mhic Donncha, Hannah Scott, Mark Harbinson, David Bell, Chris Watson

Research output: Contribution to journalMeeting abstract

Abstract

Background: Advancements in cancer therapy have significantly
improved long-term survival rates of those with breast cancer.
The addition of epirubicin treatment prior to standard trastuzumab
treatment has been shown to slow progression of disease,
reduce mortality and extend duration of survival in
patients with HER2+ Breast Cancer. However, both drugs
have off target cardiotoxic effects. Currently echocardiography
is the only standardised diagnostic measure for detecting cardiac
dysfunction. However, this is often after significant irreversible
cardiac damage has occurred. There is an emerging
need for blood-based biomarkers to aid in diagnosing subclinical
cardiac dysfunction and to stratify those at risk prior to
therapy.
Methods: AC16 human cardiomyocytes were treated with Epirubicin
(2.6 ug/ml) and Trastuzumab (150 ug/ml), both
together and in monotherapy, over 10 hr and 26 hr timepoints.
Cell viability was assessed via MTT cell viability assay.
Protein and gene expression of Troponin I and BNP were
assessed via western blot analysis and RT-PCR. Western blot
analysis and fluorescent microscopy staining of oxidative stress
markers was also carried out to elude to the potential mechanisms
of cardiac damage.
Results Morphological changes occurred in all cells treated
over 26 hrs, particularly with combined treatment. Cardiomyocytes
treated with epirubicin alone showed the most significant
reduction in cell viability compared to control (p £
0.01**). Some increase in BNP and Troponin I expression was
observed in cardiomyocytes treated with both epirubicin and
trastuzumab. Pre-treatment of cardiomyocytes with recombinant
BNP ameliorated chemotherapy-induced cell death in cardiomyocytes
to some degree, however the effect was not
significant.
Conclusion/Implications: Combined treatment with epirubicin
and trastuzumab exacerbates chemotherapy-induced cardiotoxicity.
Troponin I and BNP are biomarkers that could be used
as a diagnostic tool for prediction of subclinical chemotherapy-
induced cardiotoxicty but further work is required to
establish their true clinical utility.
Original languageEnglish
Pages (from-to)A15
Number of pages1
JournalHeart (British Cardiac Society)
Volume106
Issue numberSuppl 4
DOIs
Publication statusPublished - 01 Oct 2020

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