Rapid Response Monitoring with Circulating Tumor DNA in Metastatic Breast Cancer

项目摘要 乳腺癌是第二种最常见的恶性肿瘤，远处扩散到其他器官是一种 癌症死亡的主要原因。转移性乳腺癌的治疗仍然非常具有挑战性，需要 连续的放射监测，以确保患者在正确的时间接受正确的治疗。这一过程 通常需要重复的CT或PET成像扫描，这是昂贵的，并使患者受到潜在的不良影响 反应，包括与对比相关的过敏和器官损伤。放射监测的成本已经 急剧增加，至少与药品成本一样快。此外，因为放射检测相对来说是 罕见的是，许多人接受无效治疗的时间太长。在此期间，疾病可能会发展，留下 长期暴露于不必要的毒性并造成重大费用负担的未得到充分治疗的患者， 尤其是有了较新的靶向治疗药物课程。在光谱的另一端，耐久的患者 在他们的管理过程中，反应可能被分配给延长的放射成像。 癌症的基因组特征彻底改变了我们破译肿瘤生物学复杂性的能力 并促进更精确的癌症治疗。DNA测序的进步使检测到 肿瘤中的突变，现在是在血液中循环的肿瘤DNA(CtDNA)。无细胞循环肿瘤 有人建议将脱氧核糖核酸作为替代生物样本来确定原发肿瘤的遗传变化(S) 和/或癌症患者的转移性疾病，并作为诊断、预后和 监测对治疗的反应。然而，下一代测序(NGS)ctDNA面板价格昂贵 并且在用于疾病的连续监测时通常不报销。在本申请中，我们提出了一种 利用定制数字技术对转移性乳腺癌患者进行动态分子监测的低成本策略 滴状聚合酶链式反应(DdPCR)分析是从基线的NGS ctDNA测试中构建的。我们假设这个混血儿 该方法将为疾病进展的放射检测提供相当长的提前期，从而 对于适应性治疗的改变，将减少患者暴露于无效治疗的时间 以及暴露在不必要的毒性中。这一节约成本的努力将大大改善疾病监测。 在转移性乳腺癌患者中，减少与无效治疗相关的毒性，改善临床试验 登记并作为一种可行的方法来解决服务不足的癌症健康不平等问题 由于这些程序的成本，获得成像的机会有限的人群。

Project Summary Breast cancer is the second most commonly diagnosed malignancy and distant spread to other organs is a leading cause of cancer death. The treatment of metastatic breast cancer remains very challenging and requires serial radiological monitoring to ensure that the patient is on the right treatment at the right time. This process typically requires repeat CT or PET imaging scans which are expensive and subject patients to potential adverse reactions, including contrast-related allergies and organ damage. The cost of radiological monitoring has increased dramatically, at least as rapid as drug costs. Furthermore, because the radiological testing is relatively infrequent, many stay on ineffective treatments too long. During this period the disease may progress, leaving the patient under-treated with prolonged exposure to unnecessary toxicities and at significant cost burden, especially with newer targeted-therapy drug classes. At the other end of the spectrum, patients with durable response may be assigned to prolonged radiological imaging over the course of their management. Genomic characterization of cancer has revolutionized our ability to decipher the complexities of tumor biology and promote more precise cancer treatments. Advances in DNA sequencing have enabled the detection of mutations in the tumor and now in tumor DNA that circulate in the blood (ctDNA). Cell-free circulating tumor DNA has been proposed as a surrogate biological sample to define the genetic change(s) of a primary tumor and/or metastatic disease in a cancer patient, and to serve as a biomarker for diagnosis, prognostication, and monitoring of response to therapy. However, next generation sequencing (NGS) ctDNA panels are expensive and are typically not reimbursed when used for serial monitoring of disease. In this application we propose a low-cost strategy for dynamic molecular monitoring of metastatic breast cancer patients using bespoke digital droplet PCR (ddPCR) assays constructed from a baseline NGS ctDNA test. We hypothesize that this hybrid approach will offer a substantial lead-time over radiological detection of disease progression, allowing for adaptive treatment changes that will reduce the time patients are exposed to ineffective treatment and exposure to unnecessary toxicities. This cost-saving effort will substantially improve disease monitoring in metastatic breast cancer patients, reduce toxicity associated with ineffective treatment, improve clinical trial enrollment and serve as a viable approach to addressing cancer health inequities among underserved populations with limited access to imaging due to the cost of these procedures.