小柯机器人

美国加州大学Mark Jesus M. Magbanua团队近期取得重要工作进展，他们报道了循环肿瘤DNA在接受新辅助化疗（NAC）的高危早期HER2阴性乳腺癌中的临床意义及生物学研究。相关研究成果2023年5月4日在线发表于《癌细胞》杂志上。

据介绍，循环肿瘤DNA（ctDNA）分析可通过无创性肿瘤负担评估改善早期乳腺癌的治疗。

为了研究ctDNA脱落的临床意义和生物学亚型特异性差异，研究人员在I-SPY2试验中对NAC的激素受体（HR）阳性/HER2阴性乳腺癌症和三阴性乳腺癌症（TNBC）患者进行了一系列个性化ctDNA分析。TNBC患者NAC前、中、后ctDNA阳性率均高于HR阳性/HER2阴性乳腺癌患者。治疗开始后3周ctDNA的早期清除预测仅TNBC对NAC有良好反应。而ctDNA阳性与两种亚型的无远处复发生存率降低有关。相反，NAC后ctDNA阴性与改善预后相关，即使是广泛残留癌症患者。预处理肿瘤mRNA谱揭示了ctDNA脱落与细胞周期和免疫相关信号传导之间的关系。

总之，基于这些发现，I-SPY2试验将前瞻性地测试ctDNA在重定向治疗中的效用，以改善反应和预后。

附：英文原文

Title: Clinical significance and biology of circulating tumor DNA in high-risk early-stage HER2-negative breast cancer receiving neoadjuvant chemotherapy

Author: Mark Jesus M. Magbanua, Lamorna Brown Swigart, Ziad Ahmed, Rosalyn W. Sayaman, Derrick Renner, Ekaterina Kalashnikova, Gillian L. Hirst, Christina Yau, Denise M. Wolf, Wen Li, Amy L. Delson, Smita Asare, Minetta C. Liu, Kathy Albain, A. Jo Chien, Andres Forero-Torres, Claudine Isaacs, Rita Nanda, Debu Tripathy, Angel Rodriguez, Himanshu Sethi, Alexey Aleshin, Matthew Rabinowitz, Jane Perlmutter, W. Fraser Symmans, Douglas Yee, Nola M. Hylton, Laura J. Esserman, Angela M. DeMichele, Hope S. Rugo, Laura J. van ’t Veer

Issue&Volume: 2023-05-04

Abstract: Circulating tumor DNA (ctDNA) analysis may improve early-stage breast cancer treatment via non-invasive tumor burden assessment. To investigate subtype-specific differences in the clinical significance and biology of ctDNA shedding, we perform serial personalized ctDNA analysis in hormone receptor (HR)-positive/HER2-negative breast cancer and triple-negative breast cancer (TNBC) patients receiving neoadjuvant chemotherapy (NAC) in the I-SPY2 trial. ctDNA positivity rates before, during, and after NAC are higher in TNBC than in HR-positive/HER2-negative breast cancer patients. Early clearance of ctDNA 3 weeks after treatment initiation predicts a favorable response to NAC in TNBC only. Whereas ctDNA positivity associates with reduced distant recurrence-free survival in both subtypes. Conversely, ctDNA negativity after NAC correlates with improved outcomes, even in patients with extensive residual cancer. Pretreatment tumor mRNA profiling reveals associations between ctDNA shedding and cell cycle and immune-associated signaling. On the basis of these findings, the I-SPY2 trial will prospectively test ctDNA for utility in redirecting therapy to improve response and prognosis.

DOI: 10.1016/j.ccell.2023.04.008

Source: https://www.cell.com/cancer-cell/fulltext/S1535-6108(23)00134-4

Cancer Cell：《癌细胞》，创刊于2002年。隶属于细胞出版社，最新IF：38.585
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