Cardiotoxicity of anthracycline‑free targeted oncological therapies in HER2‑positive breast cancer (Review)

Abstract

Anthracycline drugs are considered to be pivotal drugs in numerous chemotherapy regimens for breast cancer. However, the cardiotoxicity associated with the treatment is an important issue to be addressed. With the emergence of increasingly diverse antitumor drugs, anthracycline-free therapies are able to reduce the cardiotoxicity caused by anthracycline drugs while ensuring that a therapeutic effect is achieved. In the present review, anthracycline-free oncological therapy regimens for the treatment of patients with human epidermal growth factor receptor 2 (HER2)-positive breast cancer and the associated cardiovascular toxicity are discussed, as well as some monitoring strategies. It is recommended that patients with HER2-positive breast cancer patients should receive adjuvant chemotherapy with single or dual-targeted therapy, with or without endocrine therapy according to the hormone receptor status determined by immunohistochemical examination. The main side effects of targeted therapy include cardiac dysfunction, hypertension and arrhythmia. According to individual risk stratification, it is recommended that patients should be periodically monitored using echocardiography, electrocardiography and serum markers, to enable the timely detection of the cardiovascular adverse reactions associated with tumor treatment, thereby preventing the morbidity and mortality caused by the cardiotoxicity of these drugs.

Multimodality Advanced Cardiovascular and Molecular Imaging for Early Detection and Monitoring of Cancer Therapy-Associated Cardiotoxicity and the Role of Artificial Intelligence and Big Data

“…Nuclear can evaluate for T cell infiltration using tracers targeting CD4, CD8 cells. Tracers directed against FAP, such as 68 Ga-FAPI has been shown to be increased in an animal model of checkpoint inhibitor myocarditis. Evaluation of pericarditis (bottom left), a complication of checkpoint inhibitors can be assessed by echo for detection of pericardial effusion, but with greater specificity MRI can identify edema and DGE.…”

“…ROS has also been shown to confer mitochondrial dysfunction. Disruption of mitochondrial membrane potential in mitochondrial dysfunction mediated by anthracycline can be evaluated by 68 Ga-Galmydar. In a rodent model, uptake of 68 Ga-Galmydar was reduced by 2-fold with anthracycline treatment compared to control and in H9c2 rat cardiomyoblasts, this was associated with activation of the apoptosis cascade (36).…”

“…Increased somatostatin receptor 2 (SSTR2) on the cell surface of inflammatory macrophages is a marker of macrophage activation. In a study of symptomatic stroke patients, increased uptake of SSTR2 in culprit vessels assessed by PET tracer 68 Ga-DOTATATE was shown to predict plaque rupture (58). Thus, evaluation of SSRT2 levels in patients on ICI therapy may help identify vulnerable plaques and warrants further investigation.…”

“…Thus, evaluation of SSRT2 levels in patients on ICI therapy may help identify vulnerable plaques and warrants further investigation. The mechanisms for TKI mediated MI on the other hand are attributed to endothelial cell dysfunction and activation of apoptosis pathways, although direct evidence for MI mechanisms are still lacking, thus further research would be 68 Ga-Galmydar uptake (middle bottom). Mitochondrial damage can lead to apoptosis, which can be detected by Annexin V positivity (detected by 99m Tc-Annexin (bottom right).…”

“…It is emerging as an imaging marker for fibroblast activation and fibrosis (116,117). A PET radiotracer tracer targeting FAP is 68 Ga-FAPI. In a recent study, 68 Ga-FAPI was shown to be a potential early marker of ICI myocarditis with median standardized uptake values (SUV) 1.79 (IQR 1.62, 1.85) in myocarditis patients vs. 1.15 (IQR 0.955, 1.52) in nonmyocarditis patients (45).…”