Long-Term Effects of Anthracycline Chemotherapy on Inflammatory Cytokines, Redox Status, and Ventricular Function in Breast Cancer Survivors
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- 入组人数
- 17
- 主要终点
- Change in left ventricular ejection fraction from baseline to 10-year follow-up
研究概览
简要总结
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
详细描述
- 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. 3. 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. 4. 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. 5. 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. 6. 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. 7. 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.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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)
结局指标
主要结局
Change in left ventricular ejection fraction from baseline to 10-year follow-up
时间窗: 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.
Change in left ventricular filling pressure (E/e' ratio) from baseline to 10-year follow-up
时间窗: 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.
次要结局
- Left ventricular global longitudinal strain at 10-year follow-up(10 years after completion of chemotherapy)
- Left atrial volume index at 10-year follow-up(10 years after completion of chemotherapy)
- Right ventricular-pulmonary arterial coupling (TAPSE/PASP ratio) at 10-year follow-up(10 years after completion of chemotherapy)
- Plasma antioxidant capacity measured by ferric reducing ability of plasma assay(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(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(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(Baseline (7 days before the first anthracycline chemotherapy cycle), and day 3 after the first anthracycline chemotherapy cycle (cycle length: 21 days).)
研究者
RODRIGO CASTILLO
Associate Professor, Faculty of Medicine
University of Chile