ANTthracycline-induced Inflammation and OXidative Stress: 10-year Follow-up (ANTIOX-10)
25 de junio de 2026 actualizado 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
Descripción general del estudio
Estado
Terminado
Descripción detallada
- 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 estudio
De observación
Inscripción (Actual)
17
Criterios de participación
Los investigadores buscan personas que se ajusten a una determinada descripción, denominada criterio de elegibilidad. Algunos ejemplos de estos criterios son el estado de salud general de una persona o tratamientos previos.
Criterio de elegibilidad
Edades elegibles para estudiar
- Adulto
- Adulto Mayor
Acepta Voluntarios Saludables
No
Método de muestreo
Muestra no probabilística
Población de estudio
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.
Descripción
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)
Plan de estudios
Esta sección proporciona detalles del plan de estudio, incluido cómo está diseñado el estudio y qué mide el estudio.
¿Cómo está diseñado el estudio?
Detalles de diseño
Cohortes e Intervenciones
Grupo / Cohorte |
|---|
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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.
|
¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
|
Change in left ventricular ejection fraction from baseline to 10-year follow-up
Periodo de tiempo: 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
Periodo de tiempo: 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 resultado secundarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
|
Left ventricular global longitudinal strain at 10-year follow-up
Periodo de tiempo: 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
Periodo de tiempo: 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
Periodo de tiempo: 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
Periodo de tiempo: 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
Periodo de tiempo: 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
Periodo de tiempo: 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
Periodo de tiempo: 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).
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Colaboradores e Investigadores
Aquí es donde encontrará personas y organizaciones involucradas en este estudio.
Patrocinador
Fechas de registro del estudio
Estas fechas rastrean el progreso del registro del estudio y los envíos de resultados resumidos a ClinicalTrials.gov. Los registros del estudio y los resultados informados son revisados por la Biblioteca Nacional de Medicina (NLM) para asegurarse de que cumplan con los estándares de control de calidad específicos antes de publicarlos en el sitio web público.
Fechas importantes del estudio
Inicio del estudio (Actual)
1 de febrero de 2011
Finalización primaria (Actual)
1 de abril de 2026
Finalización del estudio (Actual)
1 de abril de 2026
Fechas de registro del estudio
Enviado por primera vez
15 de junio de 2026
Primero enviado que cumplió con los criterios de control de calidad
25 de junio de 2026
Publicado por primera vez (Actual)
2 de julio de 2026
Actualizaciones de registros de estudio
Última actualización publicada (Actual)
2 de julio de 2026
Última actualización enviada que cumplió con los criterios de control de calidad
25 de junio de 2026
Última verificación
1 de junio de 2026
Más información
Términos relacionados con este estudio
Palabras clave
Términos MeSH relevantes adicionales
- Enfermedades cardiovasculares
- Heridas y Lesiones
- Procesos Patológicos
- Neoplasias por sitio
- Neoplasias
- Enfermedades cardíacas
- Trastornos inducidos químicamente
- Enfermedades de la piel
- Enfermedades de los senos
- Efectos secundarios y reacciones adversas relacionados con los medicamentos
- Lesiones por radiación
- Condiciones Patológicas, Signos y Síntomas
- Enfermedades de la piel y del tejido conectivo
- Neoplasias de mama
- Cardiotoxicidad
Otros números de identificación del estudio
- CEC-SSMO-97-2021
Información sobre medicamentos y dispositivos, documentos del estudio
Estudia un producto farmacéutico regulado por la FDA de EE. UU.
No
Estudia un producto de dispositivo regulado por la FDA de EE. UU.
No
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