Novel Biomarkers and Echocardiography for Subclinical Cardiac Toxicity in Breast Cancer Patients Receiving Anthracyclines

Use of Novel Biomarkers and Echocardiography to Assess Subclinical Cardiac Toxicity in Breast Cancer Patients Receiving Anthracyclines

This is a pilot prospective cohort study, in adult female subjects 18-85 years old with a diagnosis of invasive breast cancer who are planned for anthracycline-inclusive chemotherapy and followed up for a time period of 6 months post completion of anthracycline chemotherapy. They will participate in blood and imaging tests with a goal of determining the best method for predicting the occurrence of cardiotoxicity in this subpopulation.

Study Overview

• Status: Unknown
• Conditions: Heart Failure; Breast Cancer; Biomarkers; Cardiotoxicity; Echocardiography; Anthracycline Induced Cardiomyopathy

Detailed Description

Anthracyclines and other chemotherapy agents are associated with cardiotoxicity. The risk of cardiac related toxicity is increased in patients with advanced age, with multiple comorbid conditions, and those needing prolonged or intensive treatment. These patients require a tailored approach to surveillance, early diagnosis and treatment of cardiac issues related to cancer therapy, with timely decision making with respect to alterations in therapy. A serum biomarker approach alone or in combination with imaging indices holds promise for early identification, risk stratification and monitoring of chemotherapy related cardiotoxicity.

Thirty-five consecutive adult females between the ages of 18-85 with diagnosis of invasive breast cancer, planned for anthracycline inclusive chemotherapy (+/- taxanes, +/- trastuzumab) will be enrolled.

A detailed medical history (interim where appropriate), physical exam, collection of blood samples for the measurement of Heart Failure (HF) biomarkers (and standard chemistry and hematology parameters), electrocardiogram and a 2D/3D echo cardiogram including the measurement of global longitudinal strain will be performed at baseline, mid chemotherapy, at the end of chemotherapy and 6 months post the completion of chemotherapy. (echocardiogram will not be done during chemotherapy).

The hypothesis being tested in this prospective trial is whether early changes in the levels of serum biomarkers of stress (N terminal pro B-type natriuretic peptide (NT-proBNP)), inflammation (ST2), necrosis (hs troponin), and fibrosis (galectin-3) will correlate with changes in sub-clinical left ventricular dysfunction as assessed by 3-dimensional (3D) echocardiogram with speckle tracking/strain in breast cancer patients receiving anthracycline based chemotherapy.

• Study Type: Observational
• Enrollment (Anticipated): 35

Contacts and Locations

Study Locations

• United States
  • New York
    • Stony Brook, New York, United States, 11738
      • Recruiting
      • Stony Brook Medicine
      • Contact: Michelle Bloom, MD; Phone Number: 631-444-2031; Email: michelle.bloom@stonybrookmedicine.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

• Sampling Method: Non-Probability Sample

Study Population

females between the ages of 18-85 with diagnosis of invasive breast cancer, planned for anthracycline inclusive chemotherapy (+/- taxanes, +/- trastuzumab).

Description

Inclusion Criteria:

1. Female subjects aged 18-85 years old
2. Biopsy-proven diagnosis of invasive breast cancer carcinoma
3. Plan for anthracycline inclusive chemotherapy (+/- taxanes, +/- trastuzumab)

Exclusion Criteria:

1. History of major heart disease at the time of breast cancer diagnosis (myocardial infarction or known left ventricular dysfunction (LVD) at baseline (defined as ejection fraction <40%)
2. History of known obstructive coronary artery disease (CAD), or coronary revascularization within the past 1 year
3. History of clinical heart failure or previous heart failure hospitalization
4. Patients with elevations in NT-pro BNP (above 3x ULN), or ST2 (above 2x ULN), galectin-3 (above 2x ULN), or hs troponin (above 2x ULN) during baseline screening
5. Patients with metastatic disease or recurrent breast cancer at diagnosis
6. History of other chemotherapy treated malignancy

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Association of Heart Failure Biomarkers with Global Longitudinal strain rate	N Terminal-proBNP, hs troponin, ST2, galectin-3 with global longitudinal strain rate	up to 35 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Prediction of initiation/change in cardiovascular medications based on serum biomarkers	NT-proBNP	up to 35 weeks
Prediction of initiation/change in cardiovascular medications based on serum biomarkers	ST2	up to 35 weeks
Prediction of initiation/change in cardiovascular medications based on serum biomarkers	hs-troponin	up to 35 weeks
Prediction of initiation/change in cardiovascular medications based on serum biomarkers	galectin-3	up to 35 weeks
Prediction of cardiotoxicity based on serum biomarkers	galectin-3	up to 35 weeks
Prediction of cardiotoxicity based on serum biomarkers	NT-proBNP	up to 35 weeks
Prediction of cardiotoxicity based on serum biomarkers	hs-troponin	up to 35 weeks
Prediction of cardiotoxicity based on serum biomarkers	ST2	up to 35 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Association between modifications in chemotherapy with detection of subclinical cardiotoxicity	frequency of chemotherapy changes with subclinical cardiotoxicity	up to 10 weeks

Collaborators and Investigators

• Sponsor: Stony Brook University
• Collaborators: Gilead Sciences

Study record dates

Study Major Dates

• Study Start (Actual): April 18, 2017
• Primary Completion (Anticipated): December 1, 2020
• Study Completion (Anticipated): December 1, 2020

Study Registration Dates

• First Submitted: April 17, 2017
• First Submitted That Met QC Criteria: May 15, 2017
• First Posted (Actual): May 16, 2017

Study Record Updates

• Last Update Posted (Actual): November 1, 2019
• Last Update Submitted That Met QC Criteria: October 30, 2019
• Last Verified: October 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Chemically-Induced Disorders; Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Skin Diseases; Neoplasms; Neoplasms by Site; Wounds and Injuries; Breast Diseases; Drug-Related Side Effects and Adverse Reactions; Radiation Injuries; Breast Neoplasms; Cardiomyopathies; Cardiotoxicity
• Other Study ID Numbers: 922042

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No