Acute and Long-term Cardiovascular Toxicity After Modern Radiotherapy for Breast Cancer

Study Overview
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Brief Summary
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In Europe, breast cancer is by far the most common form of cancer diagnosed in women today, accounting for 29% of all cases. The 5-year survival rate is approximately 90%. Surgery is usually combined with radiotherapy (RT), anthracyclines, aromatase inhibitors and/or trastuzumab (Herceptin) which all have improved the life expectancy and survival in breast cancer patients. Unfortunately, RT is associated with a broad spectrum of cardiovascular diseases, which includes coronary artery disease, valvular dysfunction, congestive heart failure and stroke, and is the most common non-malignancy cause of death. During the last two decades, RT regimens for breast cancer have changed and the doses of radiation to which the heart is exposed are now potentially lower due to new and improved RT techniques. However, there are no data on whether these new regimes decrease the risk of cardiovascular disease. In this study the incidence and prevalence of cardiovascular diseases will be estimated 8 and 15 years after both conventional and laser assisted breath controlled RT, and compared with cardiovascular diseases in the general female population. A further aim is to evaluate signs and prevalence of acute cardiotoxicity from RT with the use of cardiac magnetic resonance imaging, coronary fractional flow reserve, ECG and inflammatory and cardiac biomarkers and to investigate whether these signs can predict later cardiovascular disease. The importance of traditional cardiovascular risk factors (age, hypertension, hypercholesterolemia, smoking habits and physical activity, as registered before RT) will also be evaluated.

Detailed Description
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The study is an observational study. In 2007-2012 conventional RT was part of the common treatment regime for breast cancer, but has recently been replaced by laser assisted breath controlled RT. Thus, two cohorts of breast cancer patients treated with different modes of RT will be followed for the development of cardiovascular disease for the subsequent 15 years.

Official Title
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Acute and Long-term Cardiovascular Toxicity After Modern Radiotherapy for Breast Cancer - a Prospective Longitudinal Study

Conditions
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Breast Neoplasms, Cardiovascular Diseases

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: diagnosis of breast cancer expected life-expectancy above 10 years Exclusion Criteria: Not willing to participate

Ages Eligible for Study
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Minimum Age: 30 Years
Maximum Age: 70 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 |
| --- | --- |
| conventional radiotherapy<br>450 breast cancer patients treated with conventional radiotherapy with or without anthracyclines and/or trastuzumab during 2007-2012 | |
| breath controlled radiotherapy<br>350 breast cancer patients treated with laser assisted breath controlled radiotherapy with or without anthracyclines and/or trastuzumab during 2015-2017 | |
| controls<br>per participating patient 2 age-matched female controls from the HUNT-3 population (total 800) | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| incidence of cardiovascular disease | compared with corresponding estimates from the female general population (HUNT-registry data, age-matched sample) | 8 years | 
| incidence of cardiovascular disease | compared with corresponding estimates from the female general population (HUNT-registry data, age-matched sample) | 15 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Radiotherapy, Biological markers, Magnetic resonance imaging, Echocardiography, Tomography, X-Ray Computed, Risk factors, Heart, Quality of Life