转移性乳腺癌患者血清血管内皮生长因子（VEGF）与循环肿瘤细胞及其他血清生物标志物相关性的临床意义。

The clinical relevance of serum vascular endothelial growth factor (VEGF) in correlation to circulating tumor cells and other serum biomarkers in patients with metastatic breast cancer.

机构信息

Department of Gynecology and Obstetrics, Marienkrankenhaus Hamburg, Hamburg, Germany.

Department of Gynecology, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246, Hamburg, Germany.

出版信息

Breast Cancer Res Treat. 2018 Nov;172(1):93-104. doi: 10.1007/s10549-018-4882-z. Epub 2018 Jul 12.

DOI:10.1007/s10549-018-4882-z

PMID:30003393

Abstract

PURPOSE

VEGF is one of the most important angiogenesis-stimulating cytokines and has been previously shown to be overexpressed in several solid cancers. The aim of the present study was to assess the clinical relevance of serum VEGF (sVEGF) in a large cohort of metastatic breast cancer patients and to explore the relationship between sVEGF and other blood-based biomarkers.

METHODS

Two hundred fifty-three patients with metastatic breast cancer were enrolled in this prospective, multicentre study. Blood samples were collected before start of first-line or later-line treatment. sVEGF was quantified by a commercially available ELISA. Circulating tumor cells (CTCs) were detected using CellSearch and other biomarkers (EGFR, HER2, RAS p21, TIMP1, CAIX) by ELISA.

RESULTS

Levels of sVEGF were determined in all patients, with a median concentration of 231 pg/ml. After a median follow-up of 19 months, median overall survival (OS) was 10.2 months in patients with sVEGF levels above the upper quartile (i.e. 367 pg/ml), while median OS has not been reached in patients with sVEGF < 367 pg/ml (p < 0.001). Median progression-free survival (PFS) was 4.8 months for patients with sVEGF ≥ 367 pg/ml versus 9.1 months with sVEGF levels < 367 pg/ml (p < 0.001). Patients with sVEGF levels ≥ 367 pg/ml and ≥ 5 CTCs had the shortest OS, while those with sVEGF < 367 pg/ml and non-elevated CTCs had the longest OS. CTCs, grading, line of therapy and RAS p21 were independent predictors of OS. sVEGF, line of therapy and CTCs were independent predictors of PFS in the multivariate analysis.

CONCLUSIONS

Metastatic breast cancer patients with elevated levels of sVEGF have significantly worse clinical outcome. This finding supports the biological role of VEGF in breast cancer.

TRIAL REGISTRATION

Current Controlled Trials ISRCTN59722891 (DETECT).

摘要

目的

VEGF 是最重要的血管生成刺激细胞因子之一，先前已显示其在几种实体癌中过表达。本研究的目的是评估大样本转移性乳腺癌患者血清 VEGF（sVEGF）的临床相关性，并探讨 sVEGF 与其他血液生物标志物之间的关系。

方法

本前瞻性多中心研究纳入了 253 名转移性乳腺癌患者。在一线或二线治疗开始前采集血液样本。通过商业上可用的 ELISA 定量测定 sVEGF。使用 CellSearch 检测循环肿瘤细胞（CTC），并通过 ELISA 检测其他生物标志物（EGFR、HER2、RAS p21、TIMP1、CAIX）。

结果

所有患者均测定了 sVEGF 水平，中位数浓度为 231pg/ml。中位随访 19 个月后，sVEGF 水平高于上四分位数（即 367pg/ml）的患者中位总生存期（OS）为 10.2 个月，而 sVEGF<367pg/ml 的患者中位 OS 尚未达到（p<0.001）。sVEGF≥367pg/ml 的患者中位无进展生存期（PFS）为 4.8 个月，而 sVEGF 水平<367pg/ml 的患者为 9.1 个月（p<0.001）。sVEGF 水平≥367pg/ml 且≥5 个 CTCs 的患者 OS 最短，而 sVEGF<367pg/ml 且 CTCs 非升高的患者 OS 最长。CTC、分级、治疗线和 RAS p21 是 OS 的独立预测因素。多变量分析显示，sVEGF、治疗线和 CTCs 是 PFS 的独立预测因素。