Assessment of Molecular Relapse Detection in Early-Stage Breast Cancer
Assessment of Molecular Relapse Detection in Early-Stage Breast Cancer
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DOI：
10.1001/jamaoncol.2019.1838
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发表时间：
2019-10-01
期刊：
影响因子：
28.4
通讯作者：
Turner, Nicholas C.
中科院分区：
文献类型：
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作者：
Garcia-Murillas, Isaac;Chopra, Neha;Turner, Nicholas C.
本验证研究评估了循环肿瘤DNA分析在早期乳腺癌中分子复发检测的临床有效性。Key Points循环肿瘤DNA分析在早期乳腺癌中分子复发检测的临床有效性是什么？这项独立的、前瞻性的、多中心的、验证性的研究对101名早期乳腺癌妇女进行了评估，评估了循环肿瘤DNA突变跟踪，发现在随访期间检测循环肿瘤DNA与临床复发相比的中位提前时间为10.7个月，预测了所有主要乳腺癌亚型的复发。仅脑转移通过循环肿瘤DNA分析检测的频率较低，可能需要替代监测。MeaningThe研究结果表明，分子复发检测具有高水平的临床有效性，并在分子复发时开始治疗而无需等待无法治愈的转移性疾病发展的临床试验是need.ImportanceCurrent治疗治愈大多数早期原发性乳腺癌病例。然而，需要更好的技术来确定哪些患者有复发的风险。目的评价循环肿瘤DNA（ctDNA）分析用于早期乳腺癌分子复发检测的临床有效性。设计、设置和样本这项前瞻性、多中心、样本收集、验证研究于2011年11月24日至2016年10月18日在5家英国医疗中心进行，评估早期乳腺癌患者，不考虑激素受体和ERBB 2（以前称为HER 2或HER 2/neu）状态，接受新辅助化疗，随后接受手术或在辅助化疗前接受手术。该研究招募了170名女性，在101名患者中发现了突变，形成了主要队列。对144例患者的合并队列进行了次要分析，包括先前在原理证明研究中分析的43例患者。对原发性肿瘤进行测序以识别体细胞突变，并使用个性化的肿瘤特异性数字聚合酶链反应检测来监测第一年随访中每3个月和随后每6个月采集的连续血浆样本中的这些突变。主要结局和指标主要终点为无复发生存期，采用考克斯比例风险回归模型进行分析。结果在101例女性患者（平均[SD]年龄，54 [11]岁）的主要队列中，中位随访时间为35.5个月（四分位距，27.9-43.0个月），随访期间ctDNA的检测与复发相关（风险比，25.2; 95%CI，6.7-95.6; P
This validation study assesses the clinical validity of molecular relapse detection with circulating tumor DNA analysis in early-stage breast cancer.Key PointsQuestionWhat is the clinical validity of molecular relapse detection with circulating tumor DNA analysis in early-stage breast cancer? FindingsThis independent, prospective, multicenter, validation study of 101 women early-stage breast cancer assessed circulating tumor DNA mutation tracking and found that detection of circulating tumor DNA during follow-up had a median lead time of 10.7 months compared with clinical relapse, anticipating relapse in all major breast cancer subtypes. Brain-only metastasis was detected less frequently by circulating tumor DNA analysis, potentially requiring alternative surveillance. MeaningThe findings suggest that molecular relapse detection has high levels of clinical validity, and clinical trials of treatment initiated at molecular relapse without waiting for incurable metastatic disease to develop are needed.ImportanceCurrent treatment cures most cases of early-stage, primary breast cancer. However, better techniques are required to identify which patients are at risk of relapse. ObjectiveTo assess the clinical validity of molecular relapse detection with circulating tumor DNA (ctDNA) analysis in early-stage breast cancer. Design, Setting, and ParticipantsThis prospective, multicenter, sample collection, validation study conducted at 5 United Kingdom medical centers from November 24, 2011, to October 18, 2016, assessed patients with early-stage breast cancer irrespective of hormone receptor and ERBB2 (formerly HER2 or HER2/neu) status who were receiving neoadjuvant chemotherapy followed by surgery or surgery before adjuvant chemotherapy. The study recruited 170 women, with mutations identified in 101 patients forming the main cohort. Secondary analyses were conducted on a combined cohort of 144 patients, including 43 patients previously analyzed in a proof of principle study. InterventionsPrimary tumor was sequenced to identify somatic mutations, and personalized tumor-specific digital polymerase chain reaction assays were used to monitor these mutations in serial plasma samples taken every 3 months for the first year of follow-up and subsequently every 6 months. Main Outcomes and MeasuresThe primary end point was relapse-free survival analyzed with Cox proportional hazards regression models. ResultsIn the main cohort of 101 female patients (mean [SD] age, 54 [11] years) with a median follow-up of 35.5 months (interquartile range, 27.9-43.0 months), detection of ctDNA during follow-up was associated with relapse (hazard ratio, 25.2; 95% CI, 6.7-95.6; P