Cancer survivors (CS) constitute an expanding population with underrecognized cardiometabolic risk. Despite substantial improvements in five-year survival rates, both childhood and adult survivors remain at high risk for premature morbidity and mortality. These risks are particularly pronounced following exposure to anthracyclines and/or chest radiotherapy, typically in a dose-dependent manner. In Chile, the establishment of the National Pediatric Antineoplastic Drug Program (PINDA) in 1998 marked a milestone in improving equitable access to high-quality pediatric oncology care through evidence-based treatment protocols across the public health system; the adult counterpart (PANDA) has developed diagnostic, treatment, and monitoring protocols for hematological neoplasms. Few prospective cohort or mechanistic studies have clarified risk stratification or surveillance strategies in survivor populations. The regulated, short-term activation of inflammation and innate immunity can be an adaptive and protective response to tissue injury, whereas persistent low-grade inflammation may trigger neutrophil extracellular traps formation (NETosis) and other maladaptive pathways that accelerate endothelial injury, thrombosis, and adverse cardiovascular remodeling. NETosis represents a putative immunomodulatory target for therapeutic immunomodulation in heart failure and maladaptive left ventricular remodeling in preclinical models. Concurrently, skeletal muscle-derived and hormonal mediators known as exerkines—together with increased NET activity—may modulate the pathophysiology of chronic cardiometabolic disease and contribute to cancer progression, particularly in the context of obesity, diabetes, and insulin resistance. Structured exercise is a promising non-pharmacological intervention that modulates inflammatory and metabolic pathways and may thereby help prevent non-communicable diseases, including cancer. We synthesize basic and clinical evidence to (1) define how cancer therapies promote low-grade inflammation and NETosis; (2) describe how exerkines and structured exercise influence cardiometabolic biology; and (3) evaluate exercise as a mechanistic and clinically pragmatic strategy to reduce long-term CVD risk in pediatric and adult CS.

Breast cancer is associated with systemic inflammation and increased cardiovascular risk, and anthracycline chemotherapy may contribute to persistent myocardial injury. This study aimed to evaluate acute changes in inflammatory cytokines and plasma redox status after the first anthracycline cycle and to assess long-term ventricular function after 10 years in women with breast cancer. We conducted a prospective study of 17 patients with breast cancer treated with anthracycline-based chemotherapy at Salvador Hospital, Santiago, Chile. Plasma cytokines were measured at baseline (day −7) and on day +3 after the first cycle using a MILLIPLEX Luminex^® assay. Echocardiographic assessment of left ventricular systolic and diastolic function, together with oxidative stress parameters, was performed at baseline and after 10 years of follow-up. Anthracycline exposure was associated with an acute increase in several cytokines related to inflammatory and vascular remodeling, including EGF, eotaxin, MCP-1, and VEGF. In addition, markers of redox imbalance suggested an acute pro-oxidant response after treatment. At long-term follow-up (10 years), left ventricular ejection fraction (LVEF) remained within the normal range in all patients. However, integrative echocardiographic assessment revealed impaired left ventricular relaxation, evidenced by significant reductions in the mitral inflow E/A ratio, and septal and lateral e′ velocities with respect to baseline, despite preserved estimated filling pressures. These alterations were accompanied by persistent oxidative stress, reflected by persistently elevated levels of lipid peroxidation markers, such as in vivo 8-isoprostanes. In this pilot cohort, anthracycline chemotherapy induced an early inflammatory and oxidative response that was not associated with overt long-term systolic dysfunction but was accompanied by persistent biochemical and diastolic alterations. These findings support the concept of a long-term subclinical cardiotoxic phenotype and highlight the potential value of combining echocardiographic assessment with circulating redox and inflammatory biomarkers to improve long-term cardiovascular surveillance in breast cancer survivors.