术后 ctDNA 检测与早期乳腺癌患者预后相关性的研究
Association of post-operative ctDNA detection with outcomes of patients with early breast cancers
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影响因子:8.3
分区:医学1区 Top / 肿瘤学2区
发表日期:2024 Sep
作者:
R Cutts, L Ulrich, M Beaney, M Robert, M Coakley, C Bunce, G W Crestani, S Hrebien, E Kalashnikova, H-T Wu, S Dashner, H Sethi, A Aleshin, M Liu, A Ring, A Okines, I E Smith, P Barry, N C Turner, I Garcia-Murillas
DOI:
10.1016/j.esmoop.2024.103687
摘要
在早期乳腺癌（EBC）患者中，我们旨在确定在系统性治疗前的原发手术后，通过循环肿瘤DNA（ctDNA）分析是否能检测到分子残留疾病，并评估其与复发风险及无复发生存期（RFS）的相关性。通过回顾性收集血浆样本，包括手术前、术后1-14周、辅助治疗前，以及在部分患者接受辅助治疗后采集。采用个性化、肿瘤信息驱动的多重PCR新一代测序（Signatera™）方法进行ctDNA的检测与定量。主要目标是比较检测到ctDNA与未检测到ctDNA患者的RFS及远处复发无病生存期（DRFS）。共纳入48名早期乳腺癌患者（中位年龄50.5岁），其中34例激素受体阳性/人表皮生长因子受体2阴性（HR+/HER2-）、5例HER2阳性、9例三阴性乳腺癌。结果显示，术前ctDNA检测率为64.5%（20/31），术后检测率为35.4%（17/48）。术前ctDNA检测与肿瘤等级相关（P=0.019），术后ctDNA检测与受体亚型相关（P=0.01）。术后ctDNA阳性患者的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虽较未检测者差，但差异未达统计学显著（风险比=3.7，95% CI 0.9-15.7，P=0.073）。在术前或术后检测到ctDNA的患者表现出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）趋势性下降，与两时间点均未检测到ctDNA的患者相比。ctDNA检测提前预示临床复发的中位提前期为16个月。在未经治疗的早期乳腺癌患者中，手术后ctDNA可被检测到。单一术后时间点未检测到ctDNA与改善的DRFS相关，支持未来关于系统性治疗减量的临床试验设计。
Abstract
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.