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.

项目总结 高血压(HTN)是乳腺癌患者最常见的心血管并发症 并且是癌症治疗期间和治疗后不良心血管事件的一个重要的可改变的危险因素。工作由我们的 小组和其他人的研究表明，HTN是治疗乳房引起心脏毒性的重要危险因素 针对肿瘤的治疗，包括蒽环类药物和人表皮生长因子受体2(HER2) 药物，在接受这些治疗的患者中，高达20%会发生这种情况，并出现左半身减少 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， 干扰根治性癌症治疗的实施，恶化癌症预后，并导致持续性损害 乳腺癌长期存活者的心肺健康状况。心血管疾病现在是导致 乳腺癌幸存者的发病率和死亡率，由于癌症护理的进步，他们的寿命更长， 因此，降低乳腺癌患者心血管风险的策略是非常必要的。没有标准的治疗 目前可用于预防癌症治疗期间心脏毒性的选择，并且没有指南来告知 癌症治疗中控制血压的最佳方法。多项试验表明，密集的 血压控制与心血管风险降低有关，但癌症患者除外 代表了这些试验的一个重要限制。HTN和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和降低心脏毒性风险的有力理由 HTN患者是最脆弱的，然而，以前没有试验评估密集血液的作用 压力控制对乳腺癌治疗心脏毒性的影响。因此，这项研究的目的是 评估有心脏毒性风险的HTN妇女在BC期间的强化收缩压控制 强化SBP治疗及对急性心肌梗死生物标志物(影像、功能和循环)的影响 心脏毒性。采用随机对照试验设计，130名乳腺癌患者患乳腺癌的风险增加 心脏毒性(定义为基础收缩压、≥、130毫米汞柱和使用或不使用蒽环类药物治疗- 靶向治疗)将随机分配(比例1：1)强化SBP控制(目标SBP和lt；120 mm Hg)与 开始乳腺癌治疗前的标准SBP控制(目标SBP&lt；140毫米汞柱)。目标1：评估 心脏毒性风险患者在主动BC治疗期间强化SBP控制干预的效果。 目的：评价SBP强化控制对心脏毒性的影像和功能生物标志物的影响。目标 3：评估SBP强化控制对心脏毒性循环生物标志物的影响。由此产生的结果是 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)提供功能和机制上的洞察力 加强SBP控制以减少心脏毒性风险，以及3)指导未来的心脏肿瘤学实践 关于HTN管理在改善癌症患者心血管健康方面的作用的建议。