背景:血管生成对肿瘤的发展至关重要,programming,和转移。血管生成最重要的调节因子是血管内皮生长因子(VEGF)家族,参与肿瘤微环境的多种途径。这项研究的目的是研究VEGF家族在转移性乳腺癌患者中的预后价值。重点是神经纤毛蛋白-1(NRP-1)和胎盘生长因子(PlGF)。
方法:在一项II期一线贝伐单抗加化疗试验中,使用65例转移性HER2阴性乳腺癌患者的基线血浆样本对VEGF家族的8个成员进行分析。将患者分为两组,高或低,根据每个VEGF家族成员的中位数。测定每个VEGF家族成员的无进展生存期(PFS)和总生存期(OS)。
结果:血浆NRP-1和PlGF水平低的患者的OS比血浆水平高的患者长[多变量校正风险比(HR)2.54(95%置信区间(CI)1.11-5.82,p=0.02)和3.11(95%CI1.30-7.47,p=0.01),分别]。NRP-1和PlGF水平均较低的患者的OS明显较长,HR为6.24(95%CI1.97-19.76,p=0.002)。此外,与低水平组相比,高基线NRP-1水平显著缩短PFS[多变量校正HR2.90(95%CI1.02-8.28,p=0.04)]。高基线血管内皮生长因子受体-2水平与较长的PFS相关[多变量校正HR0.43(95%CI0.19-0.98,p=0.04)].
结论:尤其是NRP-1和PlGF在接受贝伐单抗-紫杉烷联合治疗的转移性乳腺癌患者中具有预后潜力。血浆NRP-1或PlGF水平低的患者比血浆水平高的患者具有更长的OS。具有低NRP-1和PlGF水平的患者似乎具有优异的长期存活。
背景:ClinicalTrials.gov标识符:NCT00979641,注册日期2009年9月18日。区域伦理委员会:R08142M,注册日期18/11/2008。
BACKGROUND: Angiogenesis is crucial for tumor development, progression, and metastasizing. The most important regulator of angiogenesis is the vascular endothelial growth factor (VEGF) family, which is involved in multiple pathways in tumor microenvironment. The objective of this study was to investigate the prognostic value of the VEGF family in patients treated for metastatic breast cancer. The emphasis was on neuropilin-1 (NRP-1) and placental growth factor (PlGF).
METHODS: An analysis of eight members of the VEGF family was performed using baseline plasma samples of 65 patients treated for metastatic HER2 negative breast cancer in a phase II first-line bevacizumab plus chemotherapy trial. The patients were divided into two groups, high or low, according to the median for each VEGF family member. Progression-free survival (PFS) and overall survival (OS) were determined for each VEGF family member.
RESULTS: The patients with low plasma levels of NRP-1 and PlGF had a longer OS than those with high plasma levels [multivariable adjusted hazard ratios (HRs) 2.54 (95% confidence interval (CI) 1.11-5.82, p = 0.02) and 3.11 (95% CI 1.30-7.47, p = 0.01), respectively]. The patients with low levels of both NRP-1 and PlGF had a remarkably long OS with HR of 6.24, (95% CI 1.97-19.76, p = 0.002). In addition, high baseline NRP-1 level was associated with a significantly shorter PFS [multivariable adjusted HR 2.90 (95% CI 1.02-8.28, p = 0.04)] than that in the low-level group, and a high baseline vascular endothelial growth factor receptor-2 level was associated with a longer PFS [multivariable adjusted HR 0.43 (95% CI 0.19-0.98, p = 0.04)].
CONCLUSIONS: Especially NRP-1 and PlGF have prognostic potential in metastatic breast cancer patients treated with a bevacizumab-taxane combination. Patients with low plasma levels of NRP-1 or PlGF have longer OS than patients with high levels. Patients with both low NRP-1 and PlGF levels appear to have excellent long-term survival.
BACKGROUND: ClinicalTrials.gov identifier: NCT00979641, registration date 18/09/2009. The regional Ethics Committee: R08142M, registration date 18/11/2008.