Mechanisms, Predictors, and Social Determinants of Cardiotoxicity in Breast Cancer (CCT2)

Cardiotoxicity of Cancer Therapy 2: Mechanisms, Predictors, and Social Determinants of Health in Breast Cancer Patients Treated With Doxorubicin and/or Trastuzumab

This is an observational study for patients with breast cancer that will be treated with doxorubicin (Adriamycin) and/or trastuzumab (Herceptin). The study will help the investigators learn more about how these medications affect the heart and how those effects relate to patients' medical history and social determinants of health (such as race, gender identity, education, occupation, access to health services and economic resources). Patients on this study will have echocardiograms, blood draws, and answer questions about their symptoms and activity level. Patients will be followed on this study for up to 15 years.

Study Overview

• Status: Active, not recruiting
• Conditions: Cardiovascular Diseases; Breast Cancer; Drug-Related Side Effects and Adverse Reactions; Cardiotoxicity
• Intervention / Treatment: Other: Social Determinants of Health

Detailed Description

The investigators propose a prospective longitudinal cohort of breast cancer patients treated with anthracyclines and/or trastuzumab to determine the associations between social determinants of health (SDOH) and cardiotoxicity risk and to determine whether associations between SDOH and cardiotoxicity risk differ according to race. Patients will be followed with serial echo, blood draw, and surveys every 3 months for the first year, then annually for two years. After 3 years following start of cancer therapy, patients will have study visits every other year for up to 15 years.

• Study Type: Observational
• Enrollment (Estimated): 200

Contacts and Locations

Study Locations

• United States
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Patients will be recruited from the medical oncology practices at the Abramson Cancer Center.

Description

Inclusion Criteria:

• Women older than 18 years of age
• Breast cancer with treatment plan that includes doxorubicin and/or trastuzumab
• Ability to provide written informed consent

Exclusion Criteria:

• Pregnancy at enrollment
• Inability or unwillingness to provide consent

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Doxorubicin; Patients treated with doxorubicin (Adriamycin) for breast cancer	Other: Social Determinants of Health; The study will perform detailed phenotyping of Social Determinants of Health using the National Institute of Minority Health and Health Disparities PhenX SDOH toolkit at baseline.
Trastuzumab; Patients treated with trastuzumab (Herceptin) for breast cancer	Other: Social Determinants of Health; The study will perform detailed phenotyping of Social Determinants of Health using the National Institute of Minority Health and Health Disparities PhenX SDOH toolkit at baseline.
Doxorubicin and Trastuzumab; Patients treated with both doxorubicin (Adriamycin) and trastuzumab (Herceptin) for breast cancer	Other: Social Determinants of Health; The study will perform detailed phenotyping of Social Determinants of Health using the National Institute of Minority Health and Health Disparities PhenX SDOH toolkit at baseline.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Left Ventricular Ejection Fraction (LVEF)	Absolute change in LVEF by echocardiogram at follow-up	through study completion (expected to be 15 years)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cancer therapy-related cardiac dysfunction (CTRCD)	Incidence of CTRCD defined as at least a 10% absolute change in LVEF by echocardiogram at follow-up relative to baseline to a value < 50%	through study completion (expected to be 15 years)
Symptomatic Heart Failure (HF)	Incidence of symptomatic heart failure (centrally adjudicated)	through study completion (expected to be 15 years)
Change in Longitudinal Strain	Change in longitudinal strain by echo from baseline	through study completion (expected to be 15 years)
Change in Circumferential Strain	Change in circumferential strain by echo from baseline	through study completion (expected to be 15 years)
Change in Diastolic function	Change in diastolic function defined as E/e' by echo from baseline	through study completion (expected to be 15 years)
Change in Left Ventricular (LV) Mass	Change in LV Mass by echo from baseline	through study completion (expected to be 15 years)
Change in Relative LV Wall Thickness	Change in relative LV wall thickness from baseline	through study completion (expected to be 15 years)
Change in Ventricular-Arterial Coupling	Change in Ventricular-Arterial Coupling defined as Ea/Ees by echo from baseline	through study completion (expected to be 15 years)
Change in LV Twist	Change in LV Twist measured by 3D echo from baseline	through study completion (expected to be 15 years)
Change in LV Torsion	Change in LV Torsion measured by 3D echo from baseline	through study completion (expected to be 15 years)
Change in NTproBNP	Change in NTproBNP measured in batches from banked samples from baseline.	through study completion (expected to be 15 years)
Change in high-sensitivity troponin (hsTnT)	Change in hs-TnT measured in batches from banked samples from baseline.	through study completion (expected to be 15 years)
Change in patient reported fatigue	Change in Patient Reported Outcomes Information System (PROMIS) Fatigue Score from baseline. A higher score corresponds to higher reported levels of fatigue.	through study completion (expected to be 15 years)
Change in patient reported quality of life	Change in Patient Reported Outcomes Information System (PROMIS) Global Health score from baseline. Higher scores indicate a healthier patient.	through study completion (expected to be 15 years)
Change in patient reported activity level	Change in total weekly leisure activity in METS assessed by Godin Leisure Time Exercise Questionnaire from baseline.	through study completion (expected to be 15 years)

Collaborators and Investigators

• Sponsor: Abramson Cancer Center at Penn Medicine
• Collaborators: American Heart Association
• Investigators: Principal Investigator: Bonnie Ky, MD, MSCE, University of Pennsylvania

Publications and helpful links

General Publications

• Barrett M, Wilcox NS, Huang A, Levy R, Demissei B, Narayan V, Ky B. Bearing allostatic load: insights into a more equitable future within cardio-oncology. Trends Mol Med. 2022 Dec;28(12):1040-1049. doi: 10.1016/j.molmed.2022.09.006. Epub 2022 Oct 4.

Study record dates

Study Major Dates

• Study Start (Actual): October 21, 2021
• Primary Completion (Estimated): October 1, 2039
• Study Completion (Estimated): October 1, 2039

Study Registration Dates

• First Submitted: October 12, 2021
• First Submitted That Met QC Criteria: October 12, 2021
• First Posted (Actual): October 14, 2021

Study Record Updates

• Last Update Posted (Estimated): November 6, 2025
• Last Update Submitted That Met QC Criteria: November 5, 2025
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Keywords: Social Determinants of Health; Cardio-Oncology; Cardiotoxicity of Chemotherapy
• Additional Relevant MeSH Terms: Wounds and Injuries; Pathologic Processes; Neoplasms by Site; Neoplasms; Heart Diseases; Chemically-Induced Disorders; Skin Diseases; Breast Diseases; Radiation Injuries; Pathological Conditions, Signs and Symptoms; Skin and Connective Tissue Diseases; Cardiovascular Diseases; Breast Neoplasms; Drug-Related Side Effects and Adverse Reactions; Cardiotoxicity; Population Characteristics; Health Status; Demography; Health; Social Determinants of Health
• Other Study ID Numbers: UPCC 11121

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No