Cardiac toxicity of trastuzumab in metastatic breast cancer patients previously treated with high-dose chemotherapy: a retrospective study

Abstract

HER-2 overexpression is associated to a poor prognosis in high-risk and metastatic breast cancer (MBC) patients treated with highdose chemotherapy (HDC). HER-2 status is also a predictive factor and when trastuzumab is administered in combination with or sequentially to chemotherapy, a significant disease-free and/or overall survival improvement has been observed in HER-2 þ early and MBC. Unfortunately, in both settings, trastuzumab is associated with an increased risk of cardiac dysfunction (CD). We have reviewed the clinical charts of HER-2-overexpressing MBC patients treated with trastuzumab after HDC. Age, baseline left ventricular ejection fraction (LVEF), radiation therapy on cardiac area, exposure to anthracycline, single or multiple transplant, high-dose agents, trastuzumab treatment duration were recorded as potential risk factors. In total, 53 patients have been included in the analysis. Median LVEF at baseline was 60.5%; at the end of trastuzumab (data available for 28 patients only), it was 55% (P ¼ 0.01). Five out of the 28 (17.9%) patients experienced CD. Two out of 53 (3.8%) patients developed a congestive heart failure. Age X50 years and multiple transplant procedure were potential risk factors for CD. The overall incidence of CD observed in this population of HER-2 þ MBC patients treated with trastuzumab after HDC is not superior to that reported with concomitant trastuzumab and anthracyclines. However, patients with age X50 years or receiving multiple course of HDC should be considered at risk for CD.

Molecular mechanisms of cardiotoxicity of tyrosine kinase inhibition

“…In four of these trials, significant trastuzumab-associated cardiotoxicity was also observed, with an increase of 5-17% in the frequency of asymptomatic decreased LVEF and of 1-3% in the incidence of symptomatic CHF 19,20 . Risk factors for the development of trastuzumab-associated cardiac dysfunction included older age, concomitant or sequential treatment with anthracyclines, and marginal or low LVEF after chemotherapy 20,21 . As most trastuzumab-treated patients do not experience decreased cardiac function, additional factors such as genetic background, co-morbidities and, possibly, immune status must influence the risk of cardiac toxicity.…”

Cardiovascular Side-Effects of Modern Cancer Therapy

“…35 Aside from prior or concurrent exposure to anthracyclines, other potential risk factors are associated with trastuzumabrelated cardiac side effects, including baseline LV ejection fraction (LVEF), prior cardiac diseases, elderly age and previous chest irradiation. 36, 37 Patients predisposed to cardiovascular risk factors (eg, smoking, hypertension, dyslipidemia, diabetes, and obesity) are more likely to experience cardiac Binding of these ligands to the HER family results in the formation of homodimers or heterodimers, leading to autophosphorylation of tyrosine residues in the cytoplasm and activation of downstream signaling pathways. Note that the specific ligand for HER2 is unknown.…”

Toxicitéat cardiovasculaire des traitements antitumoraux

“…Dans une étude rétrospective portant sur 53 patientes, Bengala retrouve un âge > 50 ans et une polychimiothérapie préalable comme facteurs de risque de la toxicité cardiaque du trastuzumab (20).…”