Ispitivanje kardiotoksičnog efekta anti-HER2 terapije kod pacijenata sa karcinomom dojke

Abstract

Introduction: Anti-HER2 therapy nowadays represents the standard therapeutic approach in the treatment of HER2 positive breast cancer. Notwithstanding its beneficial, therapeutic effects in breast cancer treatment, the most important side effect of the therapy is its cardiotoxicity, manifested as asymptomatic reduction of left ventricular ejection fraction, but it rarely produces evident heart failure. The aim of this study was to investigate cardiotoxic effects of anti-HER2 therapy (trastuzumab and lapatinib) in HER2 positive breast cancer patients. Method: In the period from December 2018 to February 2022, we evaluated 106 female patients with HER2 positive breast cancer, receiving anti-HER2 therapy with trastuzumab (96 patients); and lapatinib (10 patients) after trastuzumab treatment for metastatic disease. Cardiotoxic effect of the therapy was assessed based on anamnestic information, clinical examination, blood pressure and heart rate measurement, electrocardiography and echocardiography. Average values of blood pressure, heart rate, echocardiographic parameters (ejection fraction – EF; fractional shortening – FS; end-diastolic diameter – EDD; left ventricular mass – LVM) were compared at the beginning and after the therapy with trastuzumab and lapatinib. The impact of risk factors for cardiotoxicity (age, previous radiation and anthracycline therapy, cardiovascular risk factors) and the effect of betablockers, ACE inhibitors, Ca-antagonists, diuretics and statins on EF, FS, EDD and LVM were investigated. Blood pressure measurement was performed with sphygmomanometers, after Riva-Rocci. Standard 12-lead electrocardiography was employed. Standard two-dimensional echocardiography was done on an ACUSON SC2000 ultrasound system. Ejection fraction (EF%) was determined using the Simpson's biplane method. Results: In 96 studied patients, with the average age of 59.57 years, EF reduction after trastuzumab therapy was 1.73% (p=0.007); in 4.16% asymptomatic cardiotoxicity developed according to the EACVI and ASE criteria. Patients over 65 years of age (4.56%; p=0.002); those with VI anthracycline cycles (1.77%; p=0.048); with prior radiation therapy (6.58 %; p=0.005); and those with left breast radiation therapy (6.14%; p=0.02) had a significant EF reduction after trastuzumab therapy. Patients with risk factors Abstract: had EF reduction by 2.58% (p=0.001), with the greatest reduction observed in the obese (EF=4.02; p=0.009). Increased EDD was found in patients over 65 years of age (1.07 mm, p=0.037); those with prior radiation therapy (1.30 mm; p=0.13), particularly with the irradiated left breast (1.72 mm; p=0.032); and in those with risk factors (1.09 mm; p=0.031). LVM increased by 3.61 g (p=0.031) after trastuzumab therapy. The LVM increase occurred in those with hyperlipidemia as a risk factor (14.57 g; p=0.050) and in those who received beta-blockers (16 g; p=0.012). Conclusion: Treatment with trastuzumab has an impact on the reduction of left ventricular ejection fraction, increase of end-diastolic diameter and left ventricular mass. The observed cardiotoxicity rate was nevertheless low, and cardiotoxicity was reversible.