Evaluation of cardiac troponin dynamics as an early biomarker for anthracycline-induced cardiotoxicity

Anthracyclines are the cornerstone of adjuvant breast cancer treatment.
However, anthracyclines are known to cause irreversible damage to
cardiomyocytes. The cumulative lifetime dose of anthracyclines is an important
predictor of development of heart failure. Regardless of administering doses
below this maximum cumulative life time dose, approximately 20% of patients
develop a persistent decrease in LVEF and about 5% develops symptomatic heart
failure.
In order to attenuate the cardiotoxic effects of anthracyclines, cardiac
imaging is performed in high risk patients (e.g. patients with pre-existent
significant cardiovascular disease), including quantification of the LVEF at
baseline and during or after treatment. This is a reactive monitoring strategy,
since it does not detect early cardiac damage and identifies only advanced
cardiac injury. Cardiac troponins are specific markers for myocyte damage.
Previous studies have shown a relationship between troponin increment during
anthracycline treatment and cardiotoxicity. Measuring cardiac troponins is
therefore a promising strategy for early detection of cardiac damage. Though
current monitoring guidelines recommend sampling of cardiac troponins in
high-risk patients at baseline and throughout treatment, a standardized
approach for timing and interpretation of troponin levels is not available.
Clinical implementation of troponin measurements in monitoring protocols has
therefore been limited. The optimal timing and interpretation of the troponin
values remains unknown.
In this pilot study we aim to identify the dynamics of hs-cTnI and hs-TnT
release during and after anthracycline treatment (doxorubicine in combination
with cyclofosfamide) in breast cancer patients in order to determine what time
point is most reflective of the (total) cardiac damage.

Identification of the dynamics of hs-cTnI and hs-TnT release during and after
anthracycline treatment (doxorubicine in combination with cyclofosfamide) in
breast cancer patients in order to determine the optimal sampling time point,
most reflective of the (total) cardiac damage.

Prospective observational (pilot) study.

The patient has no direct benefit from participating in this study. The
obtained data will be used to assess the dynamics of troponin during and after
anthracycline treatment. Insight in these dynamics will contribute to using
troponin as a routine biomarker for management of anthracycline-induced
cardiotoxicity, by determining troponin sampling time point(s) and cut-off
values for future patients. Patients included in the study will be treated
according to standard local protocol with 4 cycles of doxorubicin and
cyclofosfamide followed by 12 cycles of paclitaxel. In the local protocol 11
sampling time points are scheduled for periodic laboratory check. During these
same time points an additional blood sample will be drawn (lithium heparin
tube, 4 mL). There will be no additional venapunction and no additional visit.
The additional patient burden by participation in this study is therefore
considered minimal.