术后CTDNA检测与早期乳腺癌患者结局的关联
Association of post-operative ctDNA detection with outcomes of patients with early breast cancers
影响因子:8.30000
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
摘要
在早期的乳腺癌（EBC）患者中，我们旨在确定一次手术后循环肿瘤DNA（CTDNA）分析是否在全身治疗前，确定了分子残留疾病，并与患者进行了1-14周的临时治疗，并在手术前进行了1-14周的临时治疗。使用个性化的，肿瘤的多重PCR下一代测序测定法（Signatera™）进行CTDNA检测和定量。主要目标是比较检测到的与未检测的CTDNA的患者的RF和远处复发生存（DRF）。总共48例EBC患者（中位年龄为50.5岁）[34例激素受体受体阳性/人类表皮生长因子受体2-乳腺癌（HR+/hr 2-乳腺癌），5 hers2-+hers2-+hers2+her2+ - 9 triple-9 triple，9 triple。在手术前的64.5％（20/31）患者中检测到CTDNA，手术后35.4％（17/48）检测到CTDNA。手术前的CTDNA检测与肿瘤级相关（P = 0.019），手术后的CTDNA检测与受体亚型有关（P = 0.01）。手术后检测到的CTDNA患者的DRF较差[危险比= 5.5，95％置信区间（CI）1.1-28.5，p = 0.04]。手术后检测到的CTDNA患者的RF比缺乏CTDNA检测的患者差，尽管没有统计学意义（危险比= 3.7，95％CI 0.9-15.7，p = 0.073）。术前或术后检测到的CTDNA患者的RFS趋势（危险比= 7.8、95％CI 0.9-63.7，p = 0.05）和DRFS（危险比= 6.8，95％CI 0.8-57，p = 0.07，p = 0.07），与CTDNA相比，这两个时间点都没有时间点。 ctDNA检测预期的临床复发，中间的铅时间为16个月。在接受治疗的EBC患者中，ctDNA在手术后可检测。在单个后的术后时间点上没有ctDNA与改善的DRF有关，这支持了研究系统治疗降级的未来试验的发展。
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.