Cardiotoxicity of Cancer Therapy (CCT)

Conditions

Breast Cancer

Keywords

Chemotherapy-induced cardiotoxicity, Anthracycline, Trastuzumab

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.

Anran Huang, Uğurcan Vurgun, Anthony Thompson, Patty Kuo, Maxwell Ye et al. (10 authors)

2026-04-23

10.2196/preprints.99147

Risk-guided cardioprotection with carvedilol in patients with breast cancer (CCT guide): a phase 1 randomized clinical trial.

Jung W, Hubbard RA, Smith AM, Ko K, Huang A, Wang J, Isaacs JM, Zhang L, Liu PP, Chen Z, Shah PD, Mintzer D, Bhattacharya S, Knollman HM, Clark AS, Koropeckyj-Cox D, Messinger M, Wilcox NS, Xia C, Narayan V, Upshaw JN, Armenian SH, Ky B.

2025-04-02

10.1007/s10549-025-07636-3

Sustained Increases in IGFBP-7 May Be Related to Doxorubicin in Breast Cancer Patients

Nicholas S. Wilcox, Biniyam G. Demessei, Amanda M. Smith, Joseph R. Carver, Liyong Zhang et al. (8 authors)

JACC CardioOncology2021-09-013 citations

10.1016/j.jaccao.2021.06.005

Changes in Cardiovascular Biomarkers With Breast Cancer Therapy and Associations With Cardiac Dysfunction.

Demissei BG, Hubbard RA, Zhang L, Smith AM, Sheline K, McDonald C, Narayan V, Domchek SM, DeMichele A, Shah P, Clark AS, Fox K, Matro J, Bradbury AR, Knollman H, Getz KD, Armenian SH, Januzzi JL, Tang WHW, Liu P, Ky B.

2020-01-21127 citations

10.1161/jaha.119.014708

Comprehensive Assessment of Changes in Left Ventricular Diastolic Function With Contemporary Breast Cancer Therapy

Jenica Upshaw, Brian S. Finkelman, Rebecca A. Hubbard, Amanda M. Smith, Hari K. Narayan et al. (16 authors)

JACC. Cardiovascular imaging2019-09-18142 citations

10.1016/j.jcmg.2019.07.018

Genetic Variants Associated With Cancer Therapy–Induced Cardiomyopathy

Pablo García‐Pavía, Yuri Kim, María Alejandra Restrepo-Córdoba, Ida G. Lunde, Hiroko Wakimoto et al. (52 authors)

Circulation2019-04-16328 citations

10.1161/circulationaha.118.037934

Interventions

DIAGNOSTIC_TESTEchocardiography

Prior to chemotherapy, prior to and after anthracyclines, every 6 weeks during trastuzumab, and yearly for up to 10 years.

OTHERBlood Collection

Drawn at first chemo treatment and periodically during treatment (exact schedule varies with clinically ordered treatment plan), then annually for up to 10 years. Blood is banked for future biomarker testing.

OTHERSymptoms Questionnaire

Survey collected at first chemotherapy, periodically during therapy (exact schedule determined by clinically ordered treatment regimen), and annually for up to 10 years.

Study design

Observational model

COHORT

Time perspective

PROSPECTIVE

Eligibility

Sex/Gender

FEMALE

Age

18 Years to No maximum

Healthy volunteers

No

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

Design outcomes

Primary

Measure	Time frame	Description
Cardiac dysfunction or signs or symptoms of heart failure	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

Measure	Time frame	Description
Change in quantitated Left Ventricular Ejection Fraction (LVEF)	15 years	Change in LVEF over the course of chemotherapy; incident diastolic dysfunction by echocardiography; the combined endpoint of any incident adverse cardiovascular outcome (arrhythmia, heart failure, systolic dysfunction, or diastolic dysfunction by echo)

Countries

United States

Contacts

PRINCIPAL_INVESTIGATORBonnie Ky, MD

Abramson Cancer Center

Outcome results

None listed