Quantitative Cardiac MRI for Detection of Subclinical Cardiotoxicity in Breast Cancer

 描述(申请人提供)：乳腺癌是最常见的诊断癌症，也是全球女性癌症死亡的主要原因。人表皮生长因子受体2(HER2)在25%-30%的浸润性乳腺癌中过度表达，并与高死亡率有关。在HER2+患者中，通常在接受蒽环素(即阿霉素)化疗后再使用曲妥珠单抗治疗，这大大提高了患者的存活率。然而，心血管毒性仍然是癌症治疗最具破坏性的并发症。在最近的一项大型研究中，HER2+患者调整后的3年充血性心力衰竭(CHF)或心肌病发生率为42%。为了监测潜在的心脏毒性，监测左心室射血分数(LVEF)，如果出现LVEF下降，则暂停治疗。然而，LVEF下降发生得很晚，在检测到LVEF下降时，可能已经发生了显著的心肌损伤。因此，早期检测心脏毒性将具有重大的临床意义，因为它能够启动心脏保护理论，以防止心力衰竭的发展，并使癌症治疗不间断地完成；然而，目前还没有非侵入性方法来检测亚临床心脏毒性。心脏磁共振(CMR)的最新进展使我们能够无创性地评估细胞外体积扩张、弥漫性间质纤维化、炎症和水肿的程度，这些都与化疗相关的心肌损伤直接相关。因此，我们假设CMR可以在不中断化疗的情况下，为HER2+患者提供与辅助治疗相关的早期心脏毒性的非侵入性定量证据，以设计个性化的治疗计划来管理毒性。

 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.