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ANTthracycline-induced Inflammation and OXidative Stress: 10-year Follow-up (ANTIOX-10)

25 de junho de 2026 atualizado por: RODRIGO CASTILLO, University of Chile

Long-Term Effects of Anthracycline Chemotherapy on Inflammatory Cytokines, Redox Status, and Ventricular Function in Breast Cancer Survivors

The goal of this observational study is to learn about the long-term effects of anthracycline chemotherapy on inflammation, oxidative stress, and heart function in adult women with breast cancer.

The main questions it aims to answer are:

Do inflammatory cytokine levels change after anthracycline chemotherapy and remain altered many years after treatment?
Are long-term markers of oxidative stress and antioxidant capacity associated with changes in heart structure or function after anthracycline exposure?

This study does not include a comparison group. All participants were previously treated with anthracycline-based chemotherapy as part of their standard cancer care.

Participants will:

Provide blood samples for the measurement of inflammatory cytokines and oxidative stress-related biomarkers
Undergo a clinical cardiovascular evaluation
Receive a transthoracic echocardiogram to assess heart function, including measures of systolic and diastolic function and myocardial deformation
Participate in a long-term follow-up assessment approximately 10 years after their initial cancer treatment

Visão geral do estudo

Status

Concluído

Condições

Descrição detalhada

Study design and population. This is a prospective, observational translational study including adult patients with breast cancer undergoing anthracycline-based chemotherapy at a single tertiary-care center. Patients are evaluated longitudinally to assess subclinical cardiovascular alterations associated with anthracycline exposure. All participants are managed according to standard oncologic and cardiologic care pathways.
Echocardiographic assessment. Transthoracic echocardiography is performed by experienced cardiologists following current American Society of Echocardiography (ASE) recommendations. Studies are acquired at predefined time points, including baseline (prior to anthracycline exposure) and long-term follow-up. Left ventricular systolic function is assessed using biplane left ventricular ejection fraction (LVEF) calculated by the modified Simpson method. Diastolic function parameters include transmitral inflow velocities, tissue Doppler-derived mitral annular velocities, E/e' ratio, and left atrial volume index (LAVI).
Left ventricular global longitudinal strain (GLS) is assessed at long-term follow-up using semi-automated speckle-tracking techniques. Right ventricular-pulmonary artery coupling is explored using the Tricuspid Annular Plane Systolic Excursion (TAPSE)/Pulmonary Artery Systolic Pressure (PASP) ratio. All measurements are performed offline, and segments with inadequate image quality are excluded from analysis.
Blood sample collection and processing. Peripheral venous blood samples are collected under standardized conditions at baseline (pre-anthracycline), early after chemotherapy exposure, and at long-term follow-up. Samples are obtained using chilled anticoagulant-containing tubes, centrifuged according to protocol, aliquoted, and stored at -80 °C until biochemical analyses are performed. All samples are processed under identical experimental conditions to minimize analytical variability.
Oxidative stress and antioxidant parameters. Plasma antioxidant capacity is assessed using the Ferric Reducing Ability of Plasma (FRAP) assay at predefined time points. Activities of antioxidant enzymes, including superoxide dismutase, catalase, and glutathione peroxidase, are determined in erythrocyte lysates using commercially available assay kits according to manufacturers' instructions. Lipid peroxidation and intracellular redox status are evaluated using established biochemical methods. Results are normalized to protein concentration when applicable.
Inflammatory and proinflammatory cytokines. Circulating cytokines and growth factors are quantified in plasma samples using multiplex bead-based immunoassays. Measurements are performed at baseline and early after anthracycline exposure following standardized manufacturer protocols. Analyte concentrations are calculated based on standard curves generated for each biomarker.
Data integration and quality control. Clinical, echocardiographic, and biochemical data are collected using predefined case report forms. Data quality is ensured through consistency checks and verification procedures. All laboratory analyses and imaging measurements are performed blinded to clinical outcomes.
Exploratory analyses Echocardiographic parameters are integrated with biochemical markers of oxidative stress and inflammation for exploratory mechanistic analyses aimed at identifying associations between myocardial deformation indices and biological signatures of anthracycline-related cardiotoxicity.

Tipo de estudo

Observacional

Inscrição (Real)

Critérios de participação

Os pesquisadores procuram pessoas que se encaixem em uma determinada descrição, chamada de critérios de elegibilidade. Alguns exemplos desses critérios são a condição geral de saúde de uma pessoa ou tratamentos anteriores.

Critérios de elegibilidade

Idades elegíveis para estudo

Adulto
Adulto mais velho

Aceita Voluntários Saudáveis

Não

Método de amostragem

Amostra Não Probabilística

População do estudo

Adult women with breast cancer treated at Hospital del Salvador, Santiago, Chile. Patients were consecutively recruited between 2010 and 2013 from a prospective cohort of individuals initiating anthracycline-based chemotherapy. A protocol amendment approved by the local ethics committee allowed long-term follow-up of the original cohort at 10 years for cardiovascular, inflammatory, and oxidative stress assessment.

Descrição

Inclusion Criteria:

Female patients with histologically confirmed breast cancer
Age between 18 and 75 years
Indication for anthracycline-based chemotherapy (>200 mg/m²)
Eastern Cooperative Oncology Group (ECOG) performance status 0-2
Written informed consent signed prior to study participation
Availability for baseline cardiovascular and biomarker assessment and long-term follow-up

Exclusion Criteria:

History of heart failure or left ventricular dysfunction (LVEF <53%)
Known coronary artery disease or clinically significant ischemic heart disease
History of clinically significant arrhythmias or requirement for antiarrhythmic therapy
Dilated or hypertrophic cardiomyopathy
Moderate to severe valvular heart disease (mitral or aortic stenosis or regurgitation)
Congenital heart disease (including atrial or ventricular septal defects, patent ductus arteriosus, Ebstein anomaly, tetralogy of Fallot, coarctation of the aorta)
Chronic kidney disease (creatinine >2 mg/dL)
Hepatic failure (bilirubin >3 mg/dL, albumin <3.5 g/dL, or prothrombin activity <60% in absence of anticoagulation)

Plano de estudo

Esta seção fornece detalhes do plano de estudo, incluindo como o estudo é projetado e o que o estudo está medindo.

Como o estudo é projetado?

Detalhes do projeto

Número de grupos/coortes

Coortes e Intervenções

Grupo / Coorte
Long-term anthracycline breast cancer cohort Women with histologically confirmed breast cancer who received anthracycline-based chemotherapy (>200 mg/m²) between 2010 and 2013 at Hospital Salvador, Santiago, Chile. This cohort was followed longitudinally from baseline pre-chemotherapy assessment and reassessed after 10 years. The study is observational and no therapeutic intervention was assigned as part of the protocol. Serial evaluations included echocardiographic parameters, inflammatory cytokines, oxidative stress biomarkers, and cardiac remodeling indicators.

Grupo / Coorte

Long-term anthracycline breast cancer cohort

Women with histologically confirmed breast cancer who received anthracycline-based chemotherapy (>200 mg/m²) between 2010 and 2013 at Hospital Salvador, Santiago, Chile. This cohort was followed longitudinally from baseline pre-chemotherapy assessment and reassessed after 10 years. The study is observational and no therapeutic intervention was assigned as part of the protocol. Serial evaluations included echocardiographic parameters, inflammatory cytokines, oxidative stress biomarkers, and cardiac remodeling indicators.

O que o estudo está medindo?

Medidas de resultados primários

Medida de resultado	Descrição da medida	Prazo
Change in left ventricular ejection fraction from baseline to 10-year follow-up Prazo: From baseline (7 days before the first anthracycline chemotherapy cycle) to 10 years after completion of chemotherapy	Assessment of left ventricular systolic function by biplane Simpson method using transthoracic echocardiography. Left ventricular ejection fraction (LVEF) was measured at baseline (7 days before the first cycle of anthracycline chemotherapy) and at the 10-year follow-up.	From baseline (7 days before the first anthracycline chemotherapy cycle) to 10 years after completion of chemotherapy
Change in left ventricular filling pressure (E/e' ratio) from baseline to 10-year follow-up Prazo: From baseline (7 days before the first anthracycline chemotherapy cycle) to 10 years after completion of chemotherapy	Assessment of left ventricular diastolic function using the average E/e' ratio obtained by transthoracic echocardiography. Measurements were performed at baseline (7 days before the first cycle of anthracycline chemotherapy) and at the 10-year follow-up.	From baseline (7 days before the first anthracycline chemotherapy cycle) to 10 years after completion of chemotherapy

Medidas de resultados secundários

Medida de resultado	Descrição da medida	Prazo
Left ventricular global longitudinal strain at 10-year follow-up Prazo: 10 years after completion of chemotherapy	Assessment of left ventricular global longitudinal strain (LVGLS) using speckle-tracking echocardiography at the 10-year follow-up. Baseline LVGLS measurements were not available; therefore, only long-term values were assessed.	10 years after completion of chemotherapy
Left atrial volume index at 10-year follow-up Prazo: 10 years after completion of chemotherapy	Assessment of left atrial volume index (LAVI) by transthoracic echocardiography as an indicator of long-term left atrial remodeling after anthracycline exposure.	10 years after completion of chemotherapy
Right ventricular-pulmonary arterial coupling (TAPSE/PASP ratio) at 10-year follow-up Prazo: 10 years after completion of chemotherapy	Assessment of right ventricular-pulmonary arterial coupling using the tricuspid annular plane systolic excursion (TAPSE) to pulmonary artery systolic pressure (PASP) ratio obtained by transthoracic echocardiography.	10 years after completion of chemotherapy
Plasma antioxidant capacity measured by ferric reducing ability of plasma assay Prazo: Baseline (7 days before the first anthracycline chemotherapy cycle), day 3 after the first anthracycline chemotherapy cycle (cycle length: 21 days), and 10 years after completion of chemotherapy.	Assessment of systemic antioxidant capacity using the ferric reducing ability of plasma (FRAP) assay. Plasma samples were obtained at baseline (7 days before the first anthracycline chemotherapy cycle), on day 3 after the first chemotherapy cycle , and at the 10-year follow-up.	Baseline (7 days before the first anthracycline chemotherapy cycle), day 3 after the first anthracycline chemotherapy cycle (cycle length: 21 days), and 10 years after completion of chemotherapy.
Erythrocyte antioxidant enzyme activity Prazo: Baseline (7 days before the first anthracycline chemotherapy cycle), day 3 after the first anthracycline chemotherapy cycle (cycle length: 21 days), and 10 years after completion of chemotherapy.	Assessment of erythrocyte antioxidant enzyme activity by measuring superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) activities using standardized commercial assays. These enzymes were evaluated as complementary indicators of endogenous antioxidant defense mechanisms.	Baseline (7 days before the first anthracycline chemotherapy cycle), day 3 after the first anthracycline chemotherapy cycle (cycle length: 21 days), and 10 years after completion of chemotherapy.
Markers of oxidative stress and intracellular redox status Prazo: Baseline (7 days before the first anthracycline chemotherapy cycle), day 3 after the first anthracycline chemotherapy cycle (cycle length: 21 days), and 10 years after completion of chemotherapy.	Assessment of oxidative stress by measuring plasma 8-isoprostane concentrations and intracellular redox status using the reduced-to-oxidized glutathione (GSH/GSSG) ratio.	Baseline (7 days before the first anthracycline chemotherapy cycle), day 3 after the first anthracycline chemotherapy cycle (cycle length: 21 days), and 10 years after completion of chemotherapy.
Inflammatory cytokine profile measured by multiplex immunoassay Prazo: Baseline (7 days before the first anthracycline chemotherapy cycle), and day 3 after the first anthracycline chemotherapy cycle (cycle length: 21 days).	Assessment of the systemic inflammatory cytokine profile using a validated MILLIPLEX® multiplex bead-based immunoassay based on Luminex® xMAP® technology. Plasma cytokines were measured simultaneously as a single multiplex biomarker panel comprising inflammatory cytokines and chemokines, including interleukin-1 beta (IL-1β), interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α), interleukin-10 (IL-10), monocyte chemoattractant protein-1 (MCP-1), vascular endothelial growth factor (VEGF), interferon gamma (IFN-γ), and additional analytes included in the assay. This outcome represents the overall inflammatory biomarker profile generated by a single multiplex assay rather than multiple independent outcome measures.	Baseline (7 days before the first anthracycline chemotherapy cycle), and day 3 after the first anthracycline chemotherapy cycle (cycle length: 21 days).

Colaboradores e Investigadores

É aqui que você encontrará pessoas e organizações envolvidas com este estudo.

Patrocinador

University of Chile

Datas de registro do estudo

Essas datas acompanham o progresso do registro do estudo e os envios de resumo dos resultados para ClinicalTrials.gov. Os registros do estudo e os resultados relatados são revisados pela National Library of Medicine (NLM) para garantir que atendam aos padrões específicos de controle de qualidade antes de serem publicados no site público.

Datas Principais do Estudo

Início do estudo (Real)

1 de fevereiro de 2011

Conclusão Primária (Real)

1 de abril de 2026

Conclusão do estudo (Real)

1 de abril de 2026

Datas de inscrição no estudo

Enviado pela primeira vez

15 de junho de 2026

Enviado pela primeira vez que atendeu aos critérios de CQ

25 de junho de 2026

Primeira postagem (Real)

2 de julho de 2026

Atualizações de registro de estudo

Última Atualização Postada (Real)