Department of Laboratory Medicine, University of California San Francisco, San Francisco, California.
Department of Surgery, University of California San Francisco, San Francisco, California.
Clin Cancer Res. 2024 Jun 3;30(11):2444-2451. doi: 10.1158/1078-0432.CCR-23-2928.
We previously demonstrated the clinical significance of circulating tumor DNA (ctDNA) in patients with HER2-negative breast cancer receiving neoadjuvant chemotherapy (NAC). Here, we compared its predictive and prognostic value with cell-free DNA (cfDNA) concentration measured in the same samples from the same patients.
145 patients with hormone receptor (HR)-positive/HER2-negative and 138 triple-negative breast cancer (TNBC) with ctDNA data from a previous study were included in the analysis. Associations of serial cfDNA concentration with residual cancer burden (RCB) and distant recurrence-free survival (DRFS) were examined.
In TNBC, we observed a modest negative correlation between cfDNA concentration 3 weeks after treatment initiation and RCB, but none of the other timepoints showed significant correlation. In contrast, ctDNA was significantly positively correlated with RCB at all timepoints (all R > 0.3 and P < 0.05). In the HR-positive/HER2-negative group, cfDNA concentration did not associate with response to NAC, but survival analysis showed that high cfDNA shedders at pretreatment had a significantly worse DRFS than low shedders (hazard ratio, 2.12; P = 0.037). In TNBC, the difference in survival between high versus low cfDNA shedders at all timepoints was not statistically significant. In contrast, as previously reported, ctDNA at all timepoints was significantly correlated with DRFS in both subtypes.
In TNBC, cfDNA concentrations during therapy were not strongly correlated with response or prognosis. In the HR-positive/HER2-negative group, pretreatment cfDNA concentration was prognostic for DRFS. Overall, the predictive and prognostic value of cfDNA concentration was more limited than that of ctDNA.
我们之前证明了循环肿瘤 DNA（ctDNA）在接受新辅助化疗（NAC）的 HER2 阴性乳腺癌患者中的临床意义。在这里，我们比较了其与从同一患者相同样本中测量的游离细胞 DNA（cfDNA）浓度的预测和预后价值。
对来自先前研究的 145 例激素受体（HR）阳性/HER2 阴性和 138 例三阴性乳腺癌（TNBC）患者的 ctDNA 数据进行分析。检查了连续 cfDNA 浓度与残留肿瘤负担（RCB）和远处无复发生存（DRFS）的相关性。
在 TNBC 中，我们观察到治疗开始后 3 周时 cfDNA 浓度与 RCB 之间存在适度的负相关，但其他时间点均无显著相关性。相比之下，ctDNA 与所有时间点的 RCB 均呈显著正相关（所有 R > 0.3，P < 0.05）。在 HR 阳性/HER2 阴性组中，cfDNA 浓度与 NAC 反应无关，但生存分析表明，预处理时高 cfDNA 分泌者的 DRFS 明显差于低分泌者（风险比，2.12；P = 0.037）。在 TNBC 中，高 cfDNA 分泌者与低 cfDNA 分泌者在所有时间点的生存差异均无统计学意义。相比之下，正如之前报道的那样，ctDNA 在两个亚型的所有时间点均与 DRFS 显著相关。
在 TNBC 中，治疗期间的 cfDNA 浓度与反应或预后无密切相关性。在 HR 阳性/HER2 阴性组中，预处理 cfDNA 浓度是 DRFS 的预后因素。总体而言，cfDNA 浓度的预测和预后价值比 ctDNA 更有限。
