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乳腺癌液体和标准活检中程序性细胞死亡配体 1 状态的临床相关性。

Clinical Correlations of Programmed Cell Death Ligand 1 Status in Liquid and Standard Biopsies in Breast Cancer.

机构信息

Department of Medical Oncology, Institut du Cancer Montpellier (ICM), Montpellier University, Montpellier, France.

Institut de Recherche en Cancérologie de Montpellier (IRCM), INSERM U1194, Montpellier University, Montpellier, France.

出版信息

Clin Chem. 2020 Aug 1;66(8):1093-1101. doi: 10.1093/clinchem/hvaa121.

DOI:10.1093/clinchem/hvaa121
PMID:32712650
Abstract

BACKGROUND

Data regarding the prognostic value of programmed cell death ligand 1 (PD-L1) expression on circulating tumor cells (CTCs) are lacking. However, CTCs could represent an alternative approach to serial biopsies, allowing real-time monitoring of cancer phenotype.

METHODS

We evaluated, in a dedicated prospective clinical trial, the clinicopathological correlations and prognostic value of PD-L1(+)-CTCs in 72 patients with metastatic breast cancer (MBC).

RESULTS

Eighteen of 56 patients with available archival tissue presented at least one positive (≥1%) PD-L1 tumor sample. Baseline CTCs and PD-L1(+)-CTCs were detected in 57 (79.2%) and 26 (36.1%) patients. No significant correlation was found between PD-L1 tumors and CTC expression. In univariate analysis, triple negative (TN) phenotype, number of metastatic treatments, >2 metastatic sites, ≥5 CTCs and PD-L1(+)-CTCs were significantly associated with progression-free survival, while tissue PD-L1 expression was not. In multivariate analysis, TN phenotype, number of metastatic treatments and of metastatic sites were the only 3 variables independently associated with progression-free survival. Progesterone receptor negativity, TN phenotype, >2 metastatic sites and ≥5 CTCs were significantly associated with overall survival in univariate analysis. In multivariable analysis, TN phenotype and >2 metastatic sites were the only 2 independent variables.

CONCLUSIONS

Unlike PD-L1(+)-tumor, PD-L1(+)-CTCs correlate to survival in MBC. Reappraisal of the role of PD-L1 expression by tumor tissue and by CTCs under anti-PD-1/PD-L1 treatment is necessary to evaluate its predictive value and potential role as a stratifying factor in strategies and trials for MBC patients with MBC.

CLINICAL TRIAL REGISTRATION

NCT02866149.

摘要

背景

关于循环肿瘤细胞(CTC)中程序性死亡配体 1(PD-L1)表达的预后价值的数据尚缺乏。然而,CTC 可以作为连续活检的替代方法,允许实时监测癌症表型。

方法

我们在一项专门的前瞻性临床试验中评估了 72 例转移性乳腺癌(MBC)患者中 PD-L1(+)-CTC 的临床病理相关性和预后价值。

结果

56 例有可用存档组织的患者中有 18 例至少有一个阳性(≥1%)PD-L1 肿瘤样本。57 例(79.2%)和 26 例(36.1%)患者检测到基线 CTC 和 PD-L1(+)-CTC。PD-L1 肿瘤与 CTC 表达之间无显著相关性。在单因素分析中,三阴性(TN)表型、转移性治疗次数、>2 个转移部位、≥5 个 CTC 和 PD-L1(+)-CTC 与无进展生存期显著相关,而组织 PD-L1 表达则无显著相关性。多因素分析中,TN 表型、转移性治疗次数和转移部位是与无进展生存期独立相关的 3 个变量。孕激素受体阴性、TN 表型、>2 个转移部位和≥5 个 CTC 与总生存期显著相关。在多变量分析中,TN 表型和>2 个转移部位是唯一 2 个独立变量。

结论

与 PD-L1(+)-肿瘤不同,PD-L1(+)-CTC 与 MBC 的生存相关。在抗 PD-1/PD-L1 治疗下,需要重新评估肿瘤组织和 CTC 中 PD-L1 表达的作用,以评估其预测价值和作为 MBC 患者分层因素的潜在作用。

临床试验注册

NCT02866149。

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