Cardiotoxicity due to trastuzumab in patients with breast cancer. Case series

Abstract

Background: trastuzumab-induced cardiac dysfunction is a manifestation of cardiotoxicity, usually reversible, transient and dose independent. Its early detection by transthoracic echocardiogram allows the modification of therapeutic schemes and the initiation of cardioprotective drugs.
Objective: to evaluate the presence of trastuzumab cardiotoxicity manifested as left ventricular dysfunction assessed by transthoracic echocardiogram and its evolution with trastuzumab suspension and initiation of cardioprotective drugs.
Material and methods: observational study; case series. We retrospectively selected patients who started treatment with trastuzumab for breast cancer, with at least 5 consecutive transthoracic echocardiograms and who met trastuzumab-
induced cardiac dysfunction criteria defined as the relative reduction of the left ventricular ejection fraction > 10% with respect to the baseline, with final value <53%. Age, stage of the disease, cardiovascular risk factors , number of trastuzumab
cycles, exposure time, left ventricular ejection fraction, reduction percentage and time to normalization were recorded.
Left ventricular ejection fraction was calculated by the Simpsonmethod. The numerical variables are expressed as median and range.
Results: of a total of 43 patients at risk of trastuzumab-induced cardiac dysfunction, during the period 2014-2017, results of the eight cases that met the inclusion criteria are shown. All were asymptomatic. Baseline left ventricular ejection fraction was: 63% (55-65), at the time of trastuzumab-induced cardiac dysfunction: 49% (45-52) and percentage of decrease: 22.5% (16.1 -26.2). All the patients temporarily suspended trastuzumab and they initiated enalapril (losartan if there was intolerance) and carvedilol. Left ventricular ejection fraction normalization occurred in all patients. The time between ventricular dysfunction and normalization of left ventricular ejection fraction was 49.5 days (28-166). The ventricular
dysfunction appeared early in 2 patients (cycles 5 and 6 of trastuzumab) and in the rest, between cycles 10 and 15. The patients with early manifestation had a delayed recovery of left ventricular ejection fraction (119 and 166 days
respectively). After normalization of ventricular dysfunction, all patients restarted treatment with trastuzumab while maintaining cardioprotective treatment.
Conclusions: in this number of cases, we observed two different patterns of trastuzumab-induced cardiac dysfunction, one with earlier manifestation and greater delay in left ventricular ejection fraction recovery. Cardiac dysfunction was reversible and all patients could continue treatment. It is the intention of the working group to continue investigating on this topic through observational cohort and randomized clinical studies to analyze the risk factors for the development of trastuzumab-induced cardiac dysfunction, as well as eventual preventive measures.