Imaging Markers of Subclinical Cardiotoxicity in Breast Cancer

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 DESCRIPTION (provided by applicant): Breast cancer is the most frequently diagnosed cancer and the leading cause of cancer death in women worldwide. Human epidermal growth factor receptor 2 (HER2) is overexpressed in 25-30% of invasive breast cancers and is associated with high mortality. In HER2+ patients, anthracycline (i.e. doxorubicin) chemotherapy is usually followed by treatment with trastuzumab, which has led to a dramatic improvement in survival. However, cardiovascular toxicity remains the most devastating complications of cancer treatments. In a recent large study, the adjusted 3-year incidence of congestive heart failure (CHF) or cardiomyopathy was 42% for HER2+ patients. To monitor for potential cardiotoxicity, left ventricular ejection fraction (LVEF) is monitored and if a decline in LVEF develops, therapy is withheld. However, an LVEF decline occurs very late, and significant myocardial injury may have already occurred by the time an LVEF decline is detected. Therefore, an early detection of cardiotoxicity will have significant clinical impact by enabling initiation of cardioprotective theapy to prevent development of CHF and allowing uninterrupted completion of cancer therapy; however currently there is no non-invasive method to detect subclinical cardiotoxicity. Recent advances in cardiac MR (CMR) allow non-invasive assessment of the degree of extracellular volume expansion, diffuse interstitial fibrosis, inflammation, and edema which are directly related to myocardial injury associated with chemotherapy. Therefore, we hypothesize that CMR can provide noninvasive, quantitative evidence of early cardiotoxicity associated with adjuvant therapy for HER2+ patients to devise personalized treatment planning for management of toxicity without interrupting the chemotherapy. We will perform both pre-clinical (in a swine model of cardiotoxicity) and clinical study (in HER2+ breast cancer patient) to establish role of CMR in detecting subclinical cardiotoxicity.