Long-Term Effect of Anthracycline Chemotherapy on Ventricular Function, Oxidative Stress Parameters, and Inflammatory Cytokine Profile in Patients with Breast Cancer

Abstract

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.