PO.MCB08.04 · 分子与细胞生物学
乳腺癌患者的纵向液体活检分析：临床应用价值与指南
Longitudinal liquid biopsy profiling in breast cancer patient: Clinical utility and guidelines
作者与单位 Authors & Affiliations
摘要 Abstract
中文摘要
背景：重复液体活检在转移性乳腺癌中的临床意义尚未完全确立。虽然循环肿瘤DNA（ctDNA）分析可提供可指导治疗的信息，但在初次检测阳性后其价值尚不明确。我们根据初次活检结果评估了系列ctDNA分析的临床相关性。
方法：对前瞻性STING试验（NCT04932525）中接受≥2次血浆来源ctDNA二代测序检测的患者进行分析。体细胞变异根据ESMO分子靶点临床可操作性量表（ESCAT）进行分类。在首次（BL1）与后续（≥BL2）活检之间比较突变负荷、克隆演变及新出现的可操作性改变。记录临床试验及超适应证治疗的可及性。
结果：152例患者中，77%为激素受体阳性，19%为三阴性疾病。液体活检次数为2至6次（中位数=2）。59例患者（38.8%）首次活检无信息价值；其中38例在BL2、3例在BL3转为有信息价值，14例仍无信息价值。突变总数在BL1与后续活检之间无显著差异（p = 0.274），但呈强相关（Spearman ρ = 0.65）。新出现的变异多涉及克隆性造血相关基因（TP53、DNMT3A、TET2）或耐药相关基因（RB1、BRCA）。86例患者获得临床试验或超适应证靶向治疗；其中68例（79%）由BL1已检出的改变指导，14例（9%）由新出现的突变指导。仅10例患者出现新的ESCAT I-III级改变，包括7例ESR1突变；其余涉及ERBB2、PTEN及体细胞BRCA2。4例患者获得ESCAT IV级改变。
结论：系列液体活检对初次检测无信息价值的患者最为相关，转化率达64%，因为重复检测常能获得可操作性发现。相比之下，在有信息价值的活检后重复全panel测序所增加的价值有限，芳香化酶抑制剂暴露后的ESR1突变监测除外，后者可采用成本更低的靶向检测完成。这些结果强调，再次活检的选择应权衡潜在临床影响与成本效益。
查看英文原文 English abstract
Background :The clinical impact of repeated liquid biopsies in metastatic breast cancer have not been fully established. While circulating tumor DNA (ctDNA) profiling provides actionable insights, its value after an initially positive test is uncertain. We evaluated the clinical relevance of serial ctDNA analyses according to the initial biopsy result.
Methods :Patients from the prospective STING trial (NCT04932525) who underwent ≥2 plasma-derived ctDNA next-generation sequencing assays were analyzed. Somatic variants were classified according to the ESMO Scale for Clinical Actionability of Molecular Targets (ESCAT). Mutational burden, clonal evolution, and emergent actionable alterations were compared between the first (BL1) and subsequent (≥BL2) biopsies. Clinical trial and off-label therapy access were recorded.
Results :Among 152 patients, 77% had hormone receptor-positive and 19% triple-negative disease. The number of liquid biopsies ranged from 2 to 6 (median = 2). Fifty-nine patients (38.8%) had a non-contributive first biopsy; 38 became contributive at BL2 and 3 at BL3, while 14 remained non-contributive. The total number of mutations did not differ significantly between BL1 and later biopsies (p = 0.274) but showed a strong correlation (Spearman ρ = 0.65). Newly emergent variants mostly involved clonal hematopoiesis-related ( TP53, DNMT3A, TET2 ) or resistance-associated genes ( RB1, BR CA). Eighty-six patients accessed a clinical trial or off-label targeted therapy; 68 (79%) were guided by alterations already detected at BL1 and 14 (9%) by emerging mutations. Only 10 patients developed new ESCAT I-III alterations, including 7 with ESR1 mutations; others involved ERBB2, PTEN, and somatic BRCA2. Four patients acquired ESCAT IV alterations.
Conclusions :Serial liquid biopsies are most relevant in patients with an initially non-contributive assay, with a conversion rate of 64%, as repetition frequently yields actionable findings. In contrast, repeating full-panel sequencing after a contributive biopsy provides limited added value, except for ESR1 mutation monitoring after aromatase inhibitor exposure, which could be performed using lower-cost targeted assays. These results underline that the choice of re-biopsy should balance potential clinical impact and cost-effectiveness.
利益披露 Disclosure
A. Robert, None..
A. Xu-Vuillard, None..
T. Grinda, None..
A. Italiano, None..
C. Massard, None..
E. El-Rassy, None..
A. Mouren, None..
A. Viansone, None..
B. Pistilli, None..
J. Mourato-Ribeiro, None..
C. Roussel-Simonin, None.