Mechanisms, Predictors, and Social Determinants of Cardiotoxicity in Breast Cancer

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Breast Cancer, Cardiotoxicity, Drug-Related Side Effects and Adverse Reactions, Cardiovascular Diseases

Intervention / Treatment
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* Other: Social Determinants of Health


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Doxorubicin<br>Patients treated with doxorubicin (Adriamycin) for breast cancer | Other: Social Determinants of Health<br>* 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.<br>|
| Trastuzumab<br>Patients treated with trastuzumab (Herceptin) for breast cancer | Other: Social Determinants of Health<br>* 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.<br>|
| Doxorubicin and Trastuzumab<br>Patients treated with both doxorubicin (Adriamycin) and trastuzumab (Herceptin) for breast cancer | Other: Social Determinants of Health<br>* 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.<br>|

What is the study measuring?
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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) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cardiotoxicity of Chemotherapy, Cardio-Oncology, Social Determinants of Health