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.

突然绝经诱导结合抗雌激素治疗可改善无复发情况 乳腺癌的生存率，是绝经前妇女激素护理的新标准 受体（HR）阳性乳腺癌。这种近乎完全雌激素剥夺（NCED）疗法 还使这些女性面临与早期低雌激素血症相关的器官损害的风险。 因非癌症原因导致过早绝经的女性早期低雌激素血症是 与严重的心血管（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进行临床前检测 计算机断层扫描血管造影。关于 NCED 治疗将如何影响 CV 知之甚少 数万名被诊断患有 HR 阳性乳房的绝经前妇女的健康状况 每年癌症患者都会接受 NCED 治疗。了解早期自然历史至关重要 这种风险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。给定 HR 阳性乳腺癌的患病率以及术后生存率的显着改善 乳腺癌、癌症治疗造成的长期 CV 后遗症都有可能产生影响 大量妇女并抵消了这些生存收益。我们将研究 NCED 的早期影响 在 CV 系统上识别心肌受损的临床前标志物。简历健康状况 开始 NCED 的女性将通过全面、定量的系列心脏磁力评估 两年期间的共振成像应力研究，记录两者流量的变化 小和大 CV 血管以及整体左心室结构和功能。 我们将检验一个总体假设，即绝经前妇女接受 NCED 是为了 HR- 阳性乳腺癌的 CV 下降，可以通过以下方法在临床前进行识别 目的：表征和量化微血管损伤和灌注变化的程度 早期 NCED 治疗期间有经验；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；识别潜力 接受 NCED 的患者 CV 下降的生物标志物和其他危险因素。知识点 从这些目标中得出的结果将有助于了解哪些患者面临心血管风险 NCED 的妥协。这些研究将进一步促进护理标准的发展 预测工具，用于评估接受 NCED 治疗的女性的 CV 下降，然后才出现临床明显的下降 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。