Cardiovascular Impact of Near-complete Estrogen Deprivation for Breast Cancer

近乎完全剥夺雌激素对乳腺癌的心血管影响

• 批准号: 10615786
• 负责人: Jennifer Hawthorne Jordan
• 金额: $ 61.27万
• 依托单位: WAKE FOREST UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-05-01 至 2027-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10615786
• 关键词: Age; Angiography; Antiestrogen Therapy; Antineoplastic Agents; Aorta; Atherosclerosis; Biological Markers; Blood; Blood Pressure; Blood Vessels; Cancer Burden; Cardiotoxicity; Cardiovascular Diseases; Cardiovascular system; Characteristics; Clinical; Coronary Arteriosclerosis; Descending aorta; Development; Diagnosis; EFRAC; Electrocardiogram; Endothelium; Estrogens; Ethnic Origin; Goals; Heart; Hormone Receptor; Incidence; Inflammation; Knowledge; Left; Left Ventricular Mass; Left ventricular structure; Maps; Measurement; Measures; Menopause; Myocardial; Myocardial perfusion; Natural History; Organ; Ovarian; Patients; Perfusion; Physiologic pulse; Pilot Projects; Premature Menopause; Premenopause; Prevalence; Race; Recommendation; Recurrence; Regimen; Risk; Risk Factors; Serum; Stress; Stroke Volume; Testing; Time; Toxic effect; Treatment-related toxicity; Troponin; United States; Ventricular; Woman; Women' s Health; Work; X-Ray Computed Tomography; ascending aorta; calcification; cancer survival; cancer therapy; cardiac magnetic resonance imaging; cardiovascular health; cardiovascular risk factor; coronary calcium scoring; demographics; deprivation; experience; heart damage; heart imaging; hormone receptor-positive; improved; malignant breast neoplasm; multidisciplinary; perfusion imaging; potential biomarker; pre-clinical; predictive tools; pro-brain natriuretic peptide (1-76); social health determinants; standard of care; tool; trend; triple-negative invasive breast carcinoma; vascular injury

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.

突然绝经诱导联合抗雌激素治疗可提高无复发率 是绝经前妇女激素治疗的新标准 受体（HR）阳性乳腺癌。这种近乎完全的雌激素剥夺（NCED）疗法 也使这些妇女处于与早期低雌激素血症相关的器官损害的风险中。 早期低雌激素血症的妇女与非癌原因过早绝经， 与显著心血管（CV）损害相关，包括动脉粥样硬化和 冠状动脉疾病，可以通过心肌灌注成像在临床前检测到， 计算机体层摄影血管造影术。关于NCED治疗将如何影响CV，我们知之甚少 成千上万被诊断为HR阳性乳腺癌的绝经前妇女的健康状况 每年都有癌症患者接受NCED治疗。了解早期的自然历史是至关重要的 因为与低雌激素血症相关的临床CV疾病是不可逆的。给定 HR阳性乳腺癌的患病率和以下生存率的显著改善 乳腺癌，癌症治疗的长期CV后遗症有可能同时影响 大量的妇女和抵消这些生存的收益。我们将研究NCED的早期影响 用于识别心肌受损的临床前标志物。的CV健康状况 开始NCED的女性将通过全面、定量的系列心脏磁共振成像（MRI） 两年内的共振成像应力研究，以记录两者流动的变化 小型和大型CV血管以及整体左心室结构和功能。 我们将检验总体假设，即接受NCED治疗HR的绝经前妇女- 阳性乳腺癌具有CV下降，可使用以下方法在临床前确定 目的：表征和量化微血管损伤和灌注变化的程度 在早期NCED治疗期间经历;表征和量化结构和 NCED治疗期间主动脉和左心室的功能改变;确定潜在的 接受NCED的患者中CV下降的生物标志物和其他风险因素。知识 从这些目的中得出的结论将有助于了解哪些患者存在CV风险 NCED的妥协。这些研究将进一步促进护理标准的发展 用于评估NCED女性患者CV下降的预测工具， 目标是让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。