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

项目摘要 高血压（HTN）是乳腺癌患者中最常见的心血管（CV）合并症 并且是癌症治疗期间和之后不良CV事件的重要可改变风险因素。我们的工作 研究组和其他研究表明，HTN是治疗性乳腺癌引起心脏毒性的一个重要危险因素， 癌症治疗，包括蒽环类药物和人表皮生长因子受体2（HER 2）靶向 药物，这发生在高达20%的患者接受这些治疗，并提出了减少左 心室射血分数或心力衰竭。此外，心脏毒性是主要的治疗限制性毒性， 干扰治愈性癌症治疗的实施，影响癌症的结果，并导致持续性损害 乳腺癌长期幸存者的心肺功能。心血管疾病现在是导致 由于癌症护理的进步，乳腺癌幸存者的发病率和死亡率延长， 因此，迫切需要降低乳腺癌患者CV风险的策略。无标准治疗 目前，在癌症治疗期间可选择预防心脏毒性，并且没有指导方针可以告知 癌症治疗期间血压控制的最佳方法。多项试验表明， 血压控制与CV风险降低相关，但排除癌症患者 这是这些试验的一个重要局限性。HTN和心脏毒性风险之间的关联提供了一个 优化血压控制以改善CV健康并降低心脏毒性风险的有力依据， HTN患者是最脆弱的，但是以前没有试验评估了强化血液的作用， 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 在BC期间评估有心脏毒性风险的HTN女性患者的强化收缩压（SBP）控制 治疗和强化SBP控制对以下生物标志物（成像、功能和循环）的影响 心脏毒性使用随机对照试验设计，130例乳腺癌患者的风险增加， 心脏毒性（定义为基线SBP ≥130 mm Hg和蒽环类药物治疗伴或不伴HER 2- 靶向治疗）将被随机分配（比例1：1）到强化SBP控制（目标SBP <120 mm Hg）组， 在开始乳腺癌治疗之前，标准SBP控制（目标SBP <140 mm Hg）。目标1：评估 在有心脏毒性风险的患者中，积极BC治疗期间强化SBP控制干预的有效性。 目的2：评价强化收缩压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 3：评估强化SBP控制对心脏毒性循环生物标志物的影响。结果是 研究将：1）建立关键数据，为患者强化SBP控制的临床实施提供信息 乳腺癌有心脏毒性的风险，2）提供功能和机制的见解， 加强收缩压控制以减轻心脏毒性风险，3）指导未来心脏肿瘤学实践 关于HTN管理在改善癌症患者CV健康方面的作用的建议。

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.