The Cardio-Oncology Breast Cancer Study

Study Overview
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Brief Summary
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The main objective of this randomized controlled trial is to test the association between standard cardiac risk factors, biomarkers and parameters of echocardiography, electrocardiography, and cardiac magnetic resonance imaging, (predictors) and subsequent occurrence, frequency and severity of clinical or subclinical cardiotoxicity (outcome) within and between-groups, before start of chemotherapy, during treatment and at 1, 5, and 10 years after the completion of the chemotherapy among women with early breast cancer.

Detailed Description
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Rationale for the study: Breast cancer is the most common cancer among Swedish women, accounting for a third of all cancer cases among females. The breast cancer incidence has increased from 2596 to more than 8000 breast cancer diagnosis 2011. During the past 40 years, the age-adjusted incidence has doubled. Early adjuvant therapy reduces the risk of dying with about 50%. (Early adjuvant therapies; chemotherapy, antibodies, endocrine therapy, and radiotherapy). Treatment advances have improved survival rates, but treatment-related cardiotoxicity (CT) remains a substantial problem. In general, earlier treatment of cardiotoxicity offers the best chances of preventing or ameliorating clinical cardiotoxicity. Risk factors should be modified or reduced by treating elevated blood pressure, normalizing lipids, encouraging weight reduction and smoking cessation. Patient-tailored therapy is now possible, especially given the availability of different chemotherapy regimens, safer anthracycline analogs such as liposomal doxorubicin, and cardioprotective medications such as angiotensin converting enzyme (ACE)-inhibitors, angiotensin receptor blockers, and b-blockers. It is now suggested that new cardiac biomarkers and ultrasound techniques can detect cardiotoxicity in its early, subclinical, stages. The investigators hypothesized that biomarkers can be used to detect subclinical cardiotoxicity and that detecting early signs of cardiotoxicity might reduce the number, time-to-onset, and severity of cardiotoxic events. In present proposal the investigators aim in a randomized study to compare primary cardiac preventive measurements versus standard care. Objectives of the trial: Primary objective In a randomized study to investigate the cumulative incidence of cardiotoxic events, per randomized arm, before start of chemotherapy, during treatment and at 1, 5, and 10 years after the completion of the chemotherapy. Secondary Objectives To compare the number, time-to-onset, and severity of cardiotoxic events in an experimental group assessed and treated for subclinical cardiotoxicity before start of chemotherapy, during treatment and at 1, 5, and 10 years after the completion of the chemotherapy and a control group receiving standard of care without early assessment for subclinical cardiotoxicity. Data on the same variables will be collected from both groups before start of chemotherapy, during treatment and at 1, 5, and 10 years. Data from the experimental group will be used in real time to guide therapy, but data from the control group will be not be analyzed until after the end of the study. To assess subclinical cardiotoxicity with serum concentrations of biomarkers, tissue Doppler and strain echocardiography, electrocardiography, and magnetic resonance imaging, as well as with standard cardiac risk assessment based on standard risk factors: a history of heart disease, increasing age, obesity, hypertension, diabetes mellitus, hypercholesterolemia, smoking, parasternal radiotherapy, and the cumulative dose of anthracyclines and trastuzumab. To assess the association between primary treatment of existing standard cardiac risk factors, biomarkers and parameters of echocardiography, electrocardiography, and cardiac magnetic resonance imaging, (predictors) and subsequent occurrence of clinical or subclinical cardiotoxicity of cardiotoxicity (outcome) within and between-groups, over time. To examine how a diagnosis of breast cancer and the development of cardiotoxicity influences women's quality of life.

Official Title
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Effects of Identifying and Treating Early, Subclinical Cardiotoxicity on the Long-Term Incidence of Clinical Cardiotoxicity in Women With Breast Cancer, A Prospective Randomized Study: The Cardio-Oncology Breast Cancer Study (COBC)

Conditions
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Cardiotoxicity, Cardiomyopathies, Breast Cancer

Intervention / Treatment
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* Other: Subclinical cardiotoxicity surveillance and treatment


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Women with newly diagnosed breast cancer who are eligible to receive neo-adjuvant or adjuvant chemotherapy, with or without trastuzumab, according to the guidelines for breast cancer. Written informed consent must be given. Exclusion Criteria: A history of heart disease; ischemic heart disease, arrhythmias, heart failure, and valve diseases. Previously received oncological treatment for any malignancy. Other disease or conditions that complicates or precludes the patient from following the study protocol.

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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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Observational arm<br>Participants randomized to observational arm will receive standard oncological followup and care. | |
| Experimental: Intervention arm<br>Intervention arm receives standard oncological followup and care + subclinical cardiotoxicity surveillance and treatment. | Other: Subclinical cardiotoxicity surveillance and treatment<br>* Intervention arm receives cardiology assessment and intervention.<br>* Other names: Assessment of biomarkers, echocardiography and ECG.;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Event free survival | The cumulative incidence of clinical or subclinical cardiotoxicity, per randomized arm, in women with breast cancer at 1 year after treatment with neo- or adjuvant chemotherapy. | 1 year after the completion of the chemotherapy. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Event free survival |  | 5 and 10 years after the completion of the chemotherapy. | 
| Overall survival |  | 1, 5 and 10 years after the completion of the chemotherapy. | 
| The levels of serum biomarkers (hs-Troponin T (hs-TnT), B-type natriuretic peptide (BNP)). |  | 1, 5 and 10 years after the completion of the chemotherapy. | 
| Echocardiographic global longitudinal strain |  | 1, 5 and 10 years after the completion of the chemotherapy. | 
| The quality of life |  | 1, 5 and 10 years after the completion of the chemotherapy. |