Cardiotoxicity of Cancer Therapy: Mechanisms and Predictors
Overview
- Phase
- Not Applicable
- Intervention
- Echocardiography
- Conditions
- Breast Cancer
- Sponsor
- Abramson Cancer Center at Penn Medicine
- Enrollment
- 700
- Locations
- 1
- Primary Endpoint
- Cardiac dysfunction or signs or symptoms of heart failure
- Status
- Enrolling By Invitation
- Last Updated
- 2 months ago
Overview
Brief Summary
The objective of this study is to define the clinical significance of mechanistic biomarkers (including Neuregulin-1Beta) and novel echocardiographic measures of cardiac function in predicting the incident risk of cancer therapy cardiotoxicity.
Detailed Description
The overall study objectives are: 1. To determine the longitudinal relationships between circulating markers, such as Neuregulin (NRG)-1Beta levels and incident risk of adverse cardiovascular outcomes in patients exposed to anthracycline, trastuzumab, or a combination of the two agents. We hypothesize that a sustained increase in NRG-1Beta, indicative of enhanced cardiac stress with exposure to chemotherapeutic agents, is predictive of an increased risk of cardiac dysfunction and heart failure. 2. To study the single nucleotide polymorphism (SNP)/haplotype variation in pathways of interest, such as the Neuregulin/Epidermal Growth Factor (ErbB) signaling pathway, on incident risk of adverse cardiovascular outcomes. We hypothesize that there will be SNP/haplotypes variations that are associated with incident cardiovascular outcomes. 3. To determine the longitudinal relationships between novel echocardiographic measures, such as strain and strain rate and incident cardiac dysfunction in patients exposed to anthracycline, trastuzumab, or a combination of the two agents. We hypothesize that early declines in strain and strain rate are predictive of an increased risk of future cardiac dysfunction and heart failure. 4. To explore the changes in biomarkers such as NRG-1Beta levels and the relationships with novel echocardiographic measures of cardiac function. 5. To create a biobank as a future resource for additional questions in novel biomarkers and genetics. 6. To determine the long-term effects of cancer therapy cardiotoxicity by following patients yearly for 5 years after their exposure to cancer therapy, with the option to extend up to an additional 5 years.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Age 18 years or older
- •HER-2 positive breast cancer designated to receive trastuzumab chemotherapy with or without prior exposure to anthracycline-based chemotherapy
- •Non-HER-2 positive breast cancer designated to receive treatment with an anthracycline-containing regimen
Exclusion Criteria
- •Other contraindications to trastuzumab or anthracycline chemotherapy.
- •Vulnerable populations
Arms & Interventions
Subgroup 2
Subgroup2 represents will undergo trastuzumab therapy only
Intervention: Echocardiography
Subgroup 2
Subgroup2 represents will undergo trastuzumab therapy only
Intervention: Blood Collection
Subgroup 2
Subgroup2 represents will undergo trastuzumab therapy only
Intervention: Symptoms Questionnaire
Subgroup 1
Subgroup 1 are anthracycline only treated patients.
Intervention: Echocardiography
Subgroup 1
Subgroup 1 are anthracycline only treated patients.
Intervention: Blood Collection
Subgroup 1
Subgroup 1 are anthracycline only treated patients.
Intervention: Symptoms Questionnaire
Subgroup 3
Subgroup 3 are patients that will undergo trastuzumab therapy with anthracyclines.
Intervention: Echocardiography
Subgroup 3
Subgroup 3 are patients that will undergo trastuzumab therapy with anthracyclines.
Intervention: Blood Collection
Subgroup 3
Subgroup 3 are patients that will undergo trastuzumab therapy with anthracyclines.
Intervention: Symptoms Questionnaire
Outcomes
Primary Outcomes
Cardiac dysfunction or signs or symptoms of heart failure
Time Frame: 15 years
Cardiac dysfunction. as defined according to the Cardiac Review and Evaluation Committee (CREC) criteria as a decline in LVEF of 10% to less than 55% without signs or symptoms
Secondary Outcomes
- Change in quantitated Left Ventricular Ejection Fraction (LVEF)(15 years)