Ispitivanje kardiotoksičnog efekta anti-HER2 terapije kod pacijenata sa karcinomom dojke
Докторанд
Krstić, IvanaМентор
Pejčić, IvicaЧланови комисије
Deljanin Ilić, MarinaVrbić, Svetislav
Pavlović, Milan
Popović, Lazar
Метаподаци
Приказ свих података о дисертацијиСажетак
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
echocard...iography. 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.