Cardiovascular Impact of Near-complete Estrogen Deprivation for Breast Cancer

突然绝经诱导联合抗雌激素治疗可提高无复发 乳腺癌的存活率，是激素治疗绝经前妇女的新标准 受体(HR)阳性的乳腺癌。这种几乎完全的雌激素剥夺(NCED)疗法 也使这些妇女面临与早期低雌激素血症相关的器官损害的风险。 有非癌症原因导致过早绝经的妇女的早期低雌激素血症 与显著的心血管(CV)损害相关，包括动脉粥样硬化和 冠状动脉疾病，临床前可以通过心肌灌注成像和 计算机断层血管造影术。关于NCED治疗将如何影响简历，我们知之甚少 数万名确诊为HR阳性乳房的绝经前妇女的健康状况 癌症患者每年都会接受NCED治疗。了解早期的自然历史是至关重要的。 这是因为与低雌激素血症相关的临床心血管疾病是不可逆的。vt.给出 HR阳性乳腺癌的患病率和术后生存期的显著改善 乳腺癌、癌症治疗带来的长期心血管后遗症对两者都有潜在影响 大量妇女死亡，抵消了这些生存收益。我们将研究NCED的早期影响 心动过速系统识别心肌损害的临床前标志物。的简历健康状况 启动NCED的女性将通过全面、定量的系列心脏磁学进行评估 为期两年的磁共振成像压力研究，以记录两者血流的变化 心动过速血管的大小及整体左心室的结构和功能。 我们将检验最重要的假设，即绝经前妇女接受NCED治疗HR- 阳性乳腺癌的CV下降可以在临床前使用以下方法识别 目的：描述和量化微血管损伤和血流灌注改变的程度。 在早期NCED治疗中所经历的；表征和量化结构和 接受NCED治疗时主动脉和左心室的功能改变；确定潜在的 接受NCED治疗的患者CV下降的生物标志物和其他危险因素。《知识》 根据这些目标得出的结果将有助于了解哪些患者存在心血管疾病的风险 来自NCED的妥协。这些研究将进一步促进护理标准的发展 在NCED临床表现明显之前评估NCED女性心血管指数下降的预测性工具 目标是允许妇女安全地继续接受抗肿瘤治疗，从而降低 癌症和心血管治疗相关毒性的负担。

Abrupt menopause induction together with anti-estrogen therapy improves recurrence-free survival in breast cancer and is a new standard of care for premenopausal women with hormone receptor (HR)-positive breast cancer. This near-complete estrogen deprivation (NCED) therapy also places these women at risk of organ compromise associated with early hypoestrogenemia. Early hypoestrogenemia in women with non-cancerous reasons for premature menopause is associated with significant cardiovascular (CV) compromise including atherosclerosis and coronary artery disease, which can be detected preclinically by myocardial perfusion imaging and computed tomography angiography. Less is known about how NCED therapy will impact CV health in the tens of thousands of premenopausal women diagnosed with HR-positive breast cancer each year who will see NCED therapy. It is critical to understand the early natural history of this risk because clinical CV disease related to hypoestrogenemia will not be reversible. Given the prevalence of HR-positive breast cancer and marked improvements in survival following breast cancer, long-term CV sequalae from cancer treatments have the potential to both impact large numbers of women and offset these survival gains. We will study the early impact of NCED on the CV system to identify pre-clinical markers of myocardial compromise. The CV health of women initiating NCED will be assessed by comprehensive, quantitative serial cardiac magnetic resonance imaging stress studies over a two-year period to document changes in flow of both small and large CV vessels as well as overall left ventricular structure and function. We will test the overarching hypothesis that premenopausal women receiving NCED for HR- positive breast cancer have CV declines that can be identified preclinically using the following aims: Characterize and quantify the extent of microvascular injury and perfusion changes experienced during early NCED therapy; Characterize and quantify the extent structural and functional alterations to the aorta and left ventricle while on NCED therapy; Identify potential biomarkers and additional risk factors for CV decline in patients receiving NCED. The knowledge derived from these aims will provide an understanding of which patients are at risk of CV compromise from NCED. These studies will further enable development of standard of care predictive tools to assess CV decline in women on NCED before it is clinically apparent with the goal of allowing women to safely remain on anti-neoplastic regimens and thereby lower both the burdens of cancer and cardiovascular treatment-related toxicity.