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

25. Juni 2026 aktualisiert von: 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:

  1. Do inflammatory cytokine levels change after anthracycline chemotherapy and remain altered many years after treatment?
  2. 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:

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

Studienübersicht

Status

Abgeschlossen

Bedingungen

Detaillierte Beschreibung

  1. 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.

  2. 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.

Studientyp

Beobachtungs

Einschreibung (Tatsächlich)

17

Teilnahmekriterien

Forscher suchen nach Personen, die einer bestimmten Beschreibung entsprechen, die als Auswahlkriterien bezeichnet werden. Einige Beispiele für diese Kriterien sind der allgemeine Gesundheitszustand einer Person oder frühere Behandlungen.

Zulassungskriterien

Studienberechtigtes Alter

  • Erwachsene
  • Älterer Erwachsener

Akzeptiert gesunde Freiwillige

Nein

Probenahmeverfahren

Nicht-Wahrscheinlichkeitsprobe

Studienpopulation

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.

Beschreibung

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)

Studienplan

Dieser Abschnitt enthält Einzelheiten zum Studienplan, einschließlich des Studiendesigns und der Messung der Studieninhalte.

Wie ist die Studie aufgebaut?

Designdetails

Kohorten und Interventionen

Gruppe / Kohorte
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.

Was misst die Studie?

Primäre Ergebnismessungen

Ergebnis Maßnahme
Maßnahmenbeschreibung
Zeitfenster
Change in left ventricular ejection fraction from baseline to 10-year follow-up
Zeitfenster: 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
Zeitfenster: 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

Sekundäre Ergebnismessungen

Ergebnis Maßnahme
Maßnahmenbeschreibung
Zeitfenster
Left ventricular global longitudinal strain at 10-year follow-up
Zeitfenster: 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
Zeitfenster: 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
Zeitfenster: 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
Zeitfenster: 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
Zeitfenster: 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
Zeitfenster: 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
Zeitfenster: 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).

Mitarbeiter und Ermittler

Hier finden Sie Personen und Organisationen, die an dieser Studie beteiligt sind.

Sponsor

University of Chile

Studienaufzeichnungsdaten

Diese Daten verfolgen den Fortschritt der Übermittlung von Studienaufzeichnungen und zusammenfassenden Ergebnissen an ClinicalTrials.gov. Studienaufzeichnungen und gemeldete Ergebnisse werden von der National Library of Medicine (NLM) überprüft, um sicherzustellen, dass sie bestimmten Qualitätskontrollstandards entsprechen, bevor sie auf der öffentlichen Website veröffentlicht werden.

Haupttermine studieren

Studienbeginn (Tatsächlich)

1. Februar 2011

Primärer Abschluss (Tatsächlich)

1. April 2026

Studienabschluss (Tatsächlich)

1. April 2026

Studienanmeldedaten

Zuerst eingereicht

15. Juni 2026

Zuerst eingereicht, das die QC-Kriterien erfüllt hat

25. Juni 2026

Zuerst gepostet (Tatsächlich)

2. Juli 2026

Studienaufzeichnungsaktualisierungen

Letztes Update gepostet (Tatsächlich)

2. Juli 2026

Letztes eingereichtes Update, das die QC-Kriterien erfüllt

25. Juni 2026

Zuletzt verifiziert

1. Juni 2026

Mehr Informationen

Begriffe im Zusammenhang mit dieser Studie

Schlüsselwörter

Zusätzliche relevante MeSH-Bedingungen

Andere Studien-ID-Nummern

  • CEC-SSMO-97-2021

Arzneimittel- und Geräteinformationen, Studienunterlagen

Studiert ein von der US-amerikanischen FDA reguliertes Arzneimittelprodukt

Nein

Studiert ein von der US-amerikanischen FDA reguliertes Geräteprodukt

Nein

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