Cardiotoxicity of Adjuvant Trastuzumab

Study Overview
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Brief Summary
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Trastuzumab (Herceptin®) increases the chances of cure in patients with Her-2 overexpressing early breast cancer. Unfortunately, both the chemotherapy drugs used in this setting (anthracyclines) and trastuzumab are known to cause cardiac dysfunction in a proportion of patients. Patients who develop heart problems when taking trastuzumab might have to stop this treatment, which could jeopardise their chances of cure. N-terminal pro-B-type natriuretic peptide (NT pro-BNP) is a cardiac biomarker that is measured in the blood, the levels of which have been shown to indicate the presence of heart failure. Some early research has suggested that there may be a correlation between elevated NT pro-BNP and heart damage due to cancer chemotherapy and also trastuzumab. Troponin is another substance measured in the blood that can indicate heart damage. Finally, certain variations in an individual's genetic makeup (called polymorphisms) could put them at increased risk of heart damage from trastuzumab. Here we are studying whether any of these factors (NT pro-BNP levels, troponin levels, or certain genetic polymorphisms) can accurately predict who is at highest risk of trastuzumab-related cardiotoxicity. The principal aim of this study is to evaluate the utility of NT pro-BNP as a predictive biomarker for the development of trastuzumab related cardiotoxicity (TRC). The investigators will also examine if single nucleotide polymorphisms in the HER2 gene or Fc-gamma-receptor genes predict for TRC.

Official Title
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Prediction of Cardiotoxicity Using Serum N-terminal Pro-B-type Natriuretic Peptide in Breast Cancer Patients Receiving Adjuvant Trastuzumab

Conditions
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Breast Neoplasms, Heart Failure

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Female 18 years or older Histologically confirmed, completely excised invasive breast cancer with Her-2 overexpression Primary surgery less than twelve weeks prior to registration LVEF>50% as assessed by transthoracic echocardiogram or gated heart pool scan Eastern Cooperative Oncology Group Performance Status 0-2 Adjuvant systemic treatment plan comprises at least three cycles of anthracycline chemotherapy AND 52 weeks of trastuzumab Before patient registration, informed consent must be given according to local regulations. Exclusion Criteria: Pregnancy Distant metastases from breast cancer Any systemic chemotherapy prior to study entry

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 |
| --- | --- |
| Her-2 positive ESBC<br> | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cardiotoxicity (Cardiac death; grade 3/4 arrhythmia or ischaemia; NYHA Class 3 or 4 heart failure decline in LVEF by >10% to a level <55%; decline in LVEF by >5% to a level <50%) |  | Until 6 months after completing trastuzumab |