早期评估循环肿瘤 DNA 作为原发性全身治疗期间乳腺癌患者治疗效果和预后的标志物。

Early evaluation of circulating tumor DNA as marker of therapeutic efficacy and prognosis in breast cancer patients during primary systemic therapy.

机构信息

Department of Breast Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, 710061, China.

Biobank of the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, 710061, China.

出版信息

Breast. 2024 Aug;76:103738. doi: 10.1016/j.breast.2024.103738. Epub 2024 Apr 24.

DOI:10.1016/j.breast.2024.103738

PMID:38685149

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11067540/

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).

CONCLUSION

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

我们评估了循环肿瘤 DNA（ctDNA）作为生物标志物监测乳腺癌原发系统性治疗（PST）治疗反应的潜在作用，并评估了 ctDNA 的预测价值，以进一步识别有残留疾病的患者。

方法

我们前瞻性纳入了 72 例Ⅱ-Ⅲ期乳腺癌患者的 208 个血浆样本，这些样本分别在 PST 前、治疗 2 个周期后和手术前三个时间点采集。使用定制的 128 个基因捕获面板和下一代测序检测血浆样本中的体细胞突变。评估 ctDNA 水平的早期变化与治疗反应或长期临床结局之间的相关性。

结果

72 例患者中有 37 例（51.4%）基线时可检测到 ctDNA 改变。完全缓解的患者在 PST 期间 ctDNA 水平下降更大。随后完全缓解（n=11）、部分缓解（n=11）和无反应（n=15）的患者，其变异等位基因分数（VAF）的中位相对变化分别为-97.4%、-46.7%和+21.1%（p=0.0012）。此外，PST 后肿瘤反应的最佳预测值是治疗前与首次治疗时的 VAF 相对变化（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 升高的患者相比，VAF 降低与更长的无复发生存期显著相关（HR=12.54；95%CI，2.084 至 75.42，p=0.0063）。