Intensive Blood Pressure Control During Cardiotoxic Breast Cancer Treatment (PROTECT) Trial

心脏毒性乳腺癌治疗 (PROTECT) 试验期间强化血压控制

• 批准号: 10660289
• 负责人: Anthony Francis Yu
• 金额: $ 63.42万
• 依托单位: SLOAN-KETTERING INST CAN RESEARCH
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-06-01 至 2028-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10660289
• 关键词: Address; Adrenergic beta-Antagonists; Adverse event; Algorithms; Angiotensin-Converting Enzyme Inhibitors; Anthracycline; Attenuated; Biological Markers; Blood Pressure; Breast Cancer Treatment; Breast Cancer survivor; Breast Cancer therapy; CXCL10 gene; Cardiac Myocytes; Cardiotoxicity; Cardiovascular Diseases; Cardiovascular Physiology; Cardiovascular system; Cessation of life; Clinical; Cyclic GMP; Data; Development; Epidermal Growth Factor Receptor; Event; Exclusion; Frequencies; Future; Goals; Guidelines; Heart failure; Human; Hypertension; Image; Impairment; Inflammation; Intervention; Investigation; Knowledge; Left Ventricular Ejection Fraction; Long-Term Survivors; Malignant Neoplasms; Measures; Modeling; Morbidity - disease rate; Myocarditis; Natriuretic Peptides; Oncology; Outcome; Oxygen Consumption; Patient Outcomes Assessments; Patients; Play; Prevention; Prognostic Marker; Quality of life; Random Allocation; Randomized, Controlled Trials; Recommendation; Risk; Risk Factors; Role; Safety; Stimulator of Interferon Genes; Stress; Stroke; Toxic effect; Troponin; Woman; Work; blood pressure control; cancer care; cancer initiation; cancer therapy; cardioprotection; cardiorespiratory fitness; cardiovascular health; cardiovascular risk factor; cell free DNA; chemotherapy; circulating biomarkers; clinical implementation; clinically significant; comorbidity; efficacy evaluation; high risk; hypertension control; hypertension treatment; improved; insight; malignant breast neoplasm; modifiable risk; mortality; myocardial injury; prevent; primary outcome; randomized trial; secondary outcome; standard care; targeted agent; targeted treatment; therapy development; treatment response; treatment trial; trial design

PROJECT SUMMARY Hypertension (HTN) is the most common cardiovascular (CV) comorbidity among patients with breast cancer and is an important modifiable risk factor for adverse CV events during and after cancer treatment. Work by our group and others has shown that HTN is an important risk factor for cardiotoxicity caused by curative breast cancer treatments including anthracyclines and human epidermal growth factor receptor 2 (HER2) targeted agents, which occurs in up to 20% of patients receiving these therapies and presents with a reduced left ventricular ejection fraction or heart failure. Furthermore, cardiotoxicity is a leading treatment-limiting toxicity that interferes with curative cancer treatment delivery, worsens cancer outcomes, and leads to persistent impairment of cardiorespiratory fitness in long-term survivors of breast cancer. CV disease is now a leading cause of morbidity and mortality among breast cancer survivors who are living longer due to advances in cancer care, therefore strategies to mitigate CV risk in patients with breast cancer are critically needed. No standard treatment option is currently available to prevent cardiotoxicity during cancer treatment, and no guidelines exist to inform the optimal approach to blood pressure control during cancer treatment. Multiple trials have shown that intensive blood pressure control is associated with CV risk reductions, however exclusion of patients with cancer represents an important limitation of these trials. The association between HTN and cardiotoxicity risk provide a strong rationale for optimizing blood pressure control to improve CV health and reduce cardiotoxicity risk in patients with HTN who are most vulnerable, however no previous trial has assessed the role of intensive blood pressure control on the cardiotoxic effects of breast cancer treatment. The objective of this study is therefore to evaluate intensive systolic blood pressure (SBP) control in women with HTN at risk for cardiotoxicity during BC treatment and the effects of intensive SBP control on biomarkers (imaging, functional, and circulating) of cardiotoxicity. Using a randomized controlled trial design, 130 patients with breast cancer at increased risk for cardiotoxicity (defined by baseline SBP ≥130 mm Hg and treatment with anthracyclines with or without HER2- targeted therapy) will be randomly allocated (ratio 1:1) to intensive SBP control (goal SBP <120 mm Hg) versus standard SBP control (goal SBP <140 mm Hg) prior to initiating breast cancer treatment. Aim 1: Evaluate the efficacy of an intensive SBP control intervention during active BC treatment in patients at risk for cardiotoxicity. Aim 2: Evaluate the effects of intensive SBP control on imaging and functional biomarkers of cardiotoxicity. Aim 3: Assess the effect of intensive SBP control on circulating biomarkers of cardiotoxicity. The results from this investigation will: 1) establish critical data to inform clinical implementation of intensive SBP control for patients with breast cancer at risk for cardiotoxicity, 2) provide functional and mechanistic insights into the effects of intensive SBP control on mitigation of cardiotoxicity risk, and 3) guide future cardio-oncology practice recommendations on the role of HTN management to improve CV health in patients with cancer.

项目概要 高血压（HTN）是乳腺癌患者中最常见的心血管（CV）合并症 是癌症治疗期间和治疗后不良心血管事件的重要可改变危险因素。由我们的工作 小组等人表明，高血压是治疗性乳房引起心脏毒性的重要危险因素 癌症治疗包括靶向蒽环类药物和人表皮生长因子受体 2 (HER2) 多达 20% 接受这些治疗的患者会出现这种情况，并表现为左心室减少 心室射血分数或心力衰竭。此外，心脏毒性是一种主要的治疗限制性毒性， 干扰癌症治疗的实施，使癌症结果恶化，并导致持续性损伤 乳腺癌长期幸存者的心肺健康。心血管疾病现在是导致 由于癌症护理的进步而延长了乳腺癌幸存者的发病率和死亡率， 因此，迫切需要降低乳腺癌患者心血管风险的策略。无标准治疗 目前可以选择在癌症治疗期间预防心脏毒性，并且没有指南可以告知 癌症治疗期间控制血压的最佳方法。多项试验表明，强化 血压控制与心血管风险降低相关，但排除癌症患者 代表了这些试验的一个重要局限性。 HTN 与心脏毒性风险之间的关联提供了 优化血压控制以改善心血管健康并降低心脏毒性风险的有力理由 最容易受到感染的高血压患者，但之前没有试验评估强化血液的作用 压力控制对乳腺癌治疗的心脏毒性作用。因此，本研究的目的是 评估 BC 期间有心脏毒性风险的 HTN 女性的强化收缩压 (SBP) 控制 治疗以及强化 SBP 控制对生物标志物（影像学、功能性和循环）的影响 心脏毒性。使用随机对照试验设计，130 名乳腺癌风险增加患者 心脏毒性（定义为基线 SBP ≥130 mm Hg 以及联合或不联合 HER2- 的蒽环类药物治疗 靶向治疗）将被随机分配（比例 1:1）至强化 SBP 控制（目标 SBP <120 mm Hg）与 在开始乳腺癌治疗之前进行标准 SBP 控制（目标 SBP <140 mm Hg）。目标 1：评估 在积极的 BC 治疗期间，强化 SBP 控制干预对有心脏毒性风险的患者的疗效。 目标 2：评估强化 SBP 控制对心脏毒性的影像学和功能性生物标志物的影响。目的 图 3：评估强化 SBP 控制对心脏毒性循环生物标志物的影响。由此得出的结果 调查将：1) 建立关键数据，为临床实施患者强化 SBP 控制提供信息 乳腺癌有心脏毒性的风险，2）提供对以下影响的功能和机制的见解 强化 SBP 控制可减轻心脏毒性风险，3) 指导未来的心脏肿瘤学实践 关于高血压管理在改善癌症患者心血管健康方面的作用的建议。