在早期乳腺癌 (EBC) 患者中，我们的目的是确定初次手术后、全身治疗前的循环肿瘤 DNA (ctDNA) 分析是否能够识别分子残留疾病，并与复发和无复发生存 (RFS) 风险相关。血浆回顾性收集手术前、术后 1-14 周、辅助治疗前以及辅助治疗后的一部分患者的数据。使用个性化、肿瘤信息多重 PCR 新一代测序测定 (Signatera™) 进行 ctDNA 检测和定量。主要目的是比较检测到 ctDNA 的患者与未检测到 ctDNA 的患者的 RFS 和远处无复发生存 (DRFS)。 总共 48 名 EBC 患者（中位年龄 50.5 岁）[34 激素受体阳性/人表皮生长因子包括受体 2 阴性 (HR /HER2-)、5 例 HER2、9 例三阴性乳腺癌。术前 64.5% (20/31) 的患者检测到 ctDNA，术后检测到 35.4% (17/48) 的患者。术前ctDNA检测与肿瘤分级相关（P=0.019），术后ctDNA检测与受体亚型相关（P=0.01）。术后检测到 ctDNA 的患者 DRFS 较差 [风险比 = 5.5，95% 置信区间 (CI) 1.1-28.5，P = 0.04]。术后检测到 ctDNA 的患者的 RFS 比未检测到 ctDNA 的患者差，尽管没有统计学意义（风险比 = 3.7，95% CI 0.9-15.7，P = 0.073）。术前或术后检测到 ctDNA 的患者有 RFS（风险比 = 7.8，95% CI 0.9-63.7，P = 0.05）和 DRFS（风险比 = 6.8，95% CI 0.8-57，P = 0.07）较差的趋势）与在两个时间点均未检测到 ctDNA 的患者进行比较。 ctDNA 检测预计临床复发的中位时间为 16 个月。对于初治 EBC 患者，手术后可检测到 ctDNA。单个术后时间点 ctDNA 的缺失与 DRFS 的改善相关，支持未来研究全身治疗降级试验的开发。版权所有 © 2024 作者。由爱思唯尔有限公司出版。保留所有权利。

In early breast cancer (EBC) patients, we aimed to determine whether circulating tumor DNA (ctDNA) analysis following primary surgery, before systemic therapy, identified molecular residual disease and was associated with risk of relapse and relapse-free survival (RFS).Plasma was collected, retrospectively, before surgery, 1-14 weeks post-operatively, and before adjuvant therapy, and in a subset of patients after adjuvant therapy. A personalized, tumor-informed, multiplex PCR next generation sequencing assay (Signatera™) was used for ctDNA detection and quantification. The primary objective was to compare RFS and distant recurrence-free survival (DRFS) in patients with detected versus non-detected ctDNA.A total of 48 patients with EBC (median age 50.5 years) [34 hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-), 5 HER2+, 9 triple-negative breast cancer) were included. ctDNA was detected in 64.5% (20/31) of patients before surgery, and 35.4% (17/48) after surgery. ctDNA detection before surgery was associated with tumor grade (P = 0.019), ctDNA detection after surgery was associated with receptor subtype (P = 0.01). Patients with ctDNA detected after surgery had worse DRFS [hazard ratio = 5.5, 95% confidence interval (CI) 1.1-28.5, P = 0.04]. RFS in patients with ctDNA detected after surgery was worse than in those with lack of ctDNA detection, although not statistically significant (hazard ratio = 3.7, 95% CI 0.9-15.7, P = 0.073). Patients with ctDNA detected preoperatively or post-operatively had a trend towards worse RFS (hazard ratio = 7.8, 95% CI 0.9-63.7, P = 0.05) and DRFS (hazard ratio = 6.8, 95% CI 0.8-57, P = 0.07) compared with those with ctDNA undetected at both timepoints. ctDNA detection anticipated clinical relapse with a median lead time of 16 months.In patients with treatment-naive EBC, ctDNA is detectable after surgery. The absence of ctDNA at a single post-surgical timepoint is associated with improved DRFS, supporting the development of future trials studying de-escalation of systemic therapy.Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.