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

25 czerwca 2026 zaktualizowane przez: 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

Przegląd badań

Status

Zakończony

Warunki

Szczegółowy opis

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.

Typ studiów

Obserwacyjny

Zapisy (Rzeczywisty)

Kryteria uczestnictwa

Badacze szukają osób, które pasują do określonego opisu, zwanego kryteriami kwalifikacyjnymi. Niektóre przykłady tych kryteriów to ogólny stan zdrowia danej osoby lub wcześniejsze leczenie.

Kryteria kwalifikacji

Wiek uprawniający do nauki

Dorosły
Starszy dorosły

Akceptuje zdrowych ochotników

Nie

Metoda próbkowania

Próbka bez prawdopodobieństwa

Badana populacja

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.

Opis

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 studiów

Ta sekcja zawiera szczegółowe informacje na temat planu badania, w tym sposób zaprojektowania badania i jego pomiary.

Jak projektuje się badanie?

Szczegóły projektu

Kohorty i interwencje

Grupa / Kohorta Grupa / Kohorta Grupa lub podgrupa uczestników badania obserwacyjnego ocenianego pod kątem wyników biomedycznych lub zdrowotnych.
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.

Grupa / Kohorta

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.

Co mierzy badanie?

Podstawowe miary wyniku

Miara wyniku	Opis środka	Ramy czasowe
Change in left ventricular ejection fraction from baseline to 10-year follow-up Ramy czasowe: 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 Ramy czasowe: 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

Miary wyników drugorzędnych

Miara wyniku	Opis środka	Ramy czasowe
Left ventricular global longitudinal strain at 10-year follow-up Ramy czasowe: 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 Ramy czasowe: 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 Ramy czasowe: 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 Ramy czasowe: 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 Ramy czasowe: 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 Ramy czasowe: 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 Ramy czasowe: 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).

Współpracownicy i badacze

Tutaj znajdziesz osoby i organizacje zaangażowane w to badanie.

Sponsor

University of Chile

Daty zapisu na studia

Daty te śledzą postęp w przesyłaniu rekordów badań i podsumowań wyników do ClinicalTrials.gov. Zapisy badań i zgłoszone wyniki są przeglądane przez National Library of Medicine (NLM), aby upewnić się, że spełniają określone standardy kontroli jakości, zanim zostaną opublikowane na publicznej stronie internetowej.

Główne daty studiów

Rozpoczęcie studiów (Rzeczywisty)

1 lutego 2011

Zakończenie podstawowe (Rzeczywisty)

1 kwietnia 2026

Ukończenie studiów (Rzeczywisty)

1 kwietnia 2026

Daty rejestracji na studia

Pierwszy przesłany

15 czerwca 2026

Pierwszy przesłany, który spełnia kryteria kontroli jakości

25 czerwca 2026

Pierwszy wysłany (Rzeczywisty)

2 lipca 2026

Aktualizacje rekordów badań

Ostatnia wysłana aktualizacja (Rzeczywisty)