PDF(Pubmed)
Abstract：
BACKGROUND: We assessed the potential role of serial circulating tumor DNA (ctDNA) as a biomarker to monitor treatment response to primary systemic therapy (PST) in breast cancer and evaluated the predictive value of ctDNA to further identify patients with residual disease.
METHODS: We prospectively enrolled 208 plasma samples collected at three time points (before PST, after 2 cycles of treatment, before surgery) of 72 patients with stage Ⅱ-III breast cancer. Somatic mutations in plasma samples were identified using a customized 128-gene capture panel with next-generation sequencing. The correlation between early change in ctDNA levels and treatment response or long-term clinical outcomes was assessed.
RESULTS: 37 of 72 (51.4%) patients harbored detectable ctDNA alterations at baseline. Patients with complete response showed a larger decrease in ctDNA levels during PST. The median relative change of variant allele fraction (VAF) was -97.4%, -46.7%, and +21.1% for patients who subsequently had a complete response (n = 11), partial response (n = 11), and no response (n = 15) (p = 0.0012), respectively. In addition, the relative change of VAF between the pretreatment and first on-treatment blood draw exhibited the optimal predictive value to tumor response after PST (area under the curve, AUC = 0.7448, p = 0.02). More importantly, early change of ctDNA levels during treatment have significant prognostic value for patients with BC, there was a significant correlation between early decrease of VAF and longer recurrence-free survival compared to those with an VAF increase (HR = 12.54; 95% CI, 2.084 to 75.42, p = 0.0063).
CONCLUSIONS: Early changes of ctDNA are strongly correlated with therapeutic efficacy to PST and clinical outcomes in BC patients. The integration of preoperative ctDNA evaluation could help improving the perioperative management for BC patients receiving PST.
METHODS: We prospectively enrolled 208 plasma samples collected at three time points (before PST, after 2 cycles of treatment, before surgery) of 72 patients with stage Ⅱ-III breast cancer. Somatic mutations in plasma samples were identified using a customized 128-gene capture panel with next-generation sequencing. The correlation between early change in ctDNA levels and treatment response or long-term clinical outcomes was assessed.
RESULTS: 37 of 72 (51.4%) patients harbored detectable ctDNA alterations at baseline. Patients with complete response showed a larger decrease in ctDNA levels during PST. The median relative change of variant allele fraction (VAF) was -97.4%, -46.7%, and +21.1% for patients who subsequently had a complete response (n = 11), partial response (n = 11), and no response (n = 15) (p = 0.0012), respectively. In addition, the relative change of VAF between the pretreatment and first on-treatment blood draw exhibited the optimal predictive value to tumor response after PST (area under the curve, AUC = 0.7448, p = 0.02). More importantly, early change of ctDNA levels during treatment have significant prognostic value for patients with BC, there was a significant correlation between early decrease of VAF and longer recurrence-free survival compared to those with an VAF increase (HR = 12.54; 95% CI, 2.084 to 75.42, p = 0.0063).
CONCLUSIONS: Early changes of ctDNA are strongly correlated with therapeutic efficacy to PST and clinical outcomes in BC patients. The integration of preoperative ctDNA evaluation could help improving the perioperative management for BC patients receiving PST.
摘要：
背景：我们评估了连续循环肿瘤DNA（ctDNA）作为生物标志物的潜在作用，以监测乳腺癌对初级全身治疗（PST）的治疗反应，并评估了ctDNA的预测价值，以进一步识别残留疾病的患者。
方法：我们前瞻性登记了在三个时间点收集的208个血浆样本（PST前，经过2个周期的治疗，术前）72例Ⅱ-Ⅲ期乳腺癌患者。使用定制的128基因捕获组及下一代测序鉴定血浆样品中的体细胞突变。评估ctDNA水平的早期变化与治疗反应或长期临床结果之间的相关性。
结果：72例患者中有37例（51.4%）在基线时存在可检测的ctDNA改变。具有完全反应的患者在PST期间显示出ctDNA水平的较大下降。变异等位基因分数（VAF）的中位数相对变化为-97.4％，-46.7%，随后完全缓解的患者为+21.1%(n=11)，部分响应（n=11），无反应（n=15）（p=0.0012），分别。此外,治疗前和治疗后第一次抽血之间VAF的相对变化表现出对PST后肿瘤反应的最佳预测值（曲线下面积，AUC=0.7448，p=0.02）。更重要的是,治疗期间ctDNA水平的早期变化对BC患者具有显著的预后价值，与VAF增加的患者相比,VAF的早期减少与更长的无复发生存期之间存在显著相关性(HR=12.54;95%CI,2.084~75.42,p=0.0063).
结论：早期ctDNA的变化与BC患者对PST的疗效和临床结局密切相关。术前ctDNA评估的整合有助于改善接受PST的BC患者的围手术期管理。
方法：我们前瞻性登记了在三个时间点收集的208个血浆样本（PST前，经过2个周期的治疗，术前）72例Ⅱ-Ⅲ期乳腺癌患者。使用定制的128基因捕获组及下一代测序鉴定血浆样品中的体细胞突变。评估ctDNA水平的早期变化与治疗反应或长期临床结果之间的相关性。
结果：72例患者中有37例（51.4%）在基线时存在可检测的ctDNA改变。具有完全反应的患者在PST期间显示出ctDNA水平的较大下降。变异等位基因分数（VAF）的中位数相对变化为-97.4％，-46.7%，随后完全缓解的患者为+21.1%(n=11)，部分响应（n=11），无反应（n=15）（p=0.0012），分别。此外,治疗前和治疗后第一次抽血之间VAF的相对变化表现出对PST后肿瘤反应的最佳预测值（曲线下面积，AUC=0.7448，p=0.02）。更重要的是,治疗期间ctDNA水平的早期变化对BC患者具有显著的预后价值，与VAF增加的患者相比,VAF的早期减少与更长的无复发生存期之间存在显著相关性(HR=12.54;95%CI,2.084~75.42,p=0.0063).
结论：早期ctDNA的变化与BC患者对PST的疗效和临床结局密切相关。术前ctDNA评估的整合有助于改善接受PST的BC患者的围手术期管理。
