Mäenpää Niina, Tiainen Leena, Hämäläinen Mari, Luukkaala Tiina, Tanner Minna, Lahdenperä Outi, Vihinen Pia, Karihtala Peeter, Kellokumpu-Lehtinen Pirkko-Liisa, Moilanen Eeva, Jukkola Arja
Faculty of Medicine and Health Technology, Tampere University, FI-33014, Tampere, Finland.
Department of Oncology, Tays Cancer Centre, Tampere University Hospital, FICAN Mid, Teiskontie 35, FI-33521, Tampere, Finland.
BMC Cancer. 2024 Mar 11;24(1):331. doi: 10.1186/s12885-024-12070-7.
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).
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.
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)].
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.
ClinicalTrials.gov identifier: NCT00979641, registration date 18/09/2009. The regional Ethics Committee: R08142M, registration date 18/11/2008.
血管生成对于肿瘤的发生、发展及转移至关重要。血管生成最重要的调节因子是血管内皮生长因子（VEGF）家族，其参与肿瘤微环境中的多种信号通路。本研究旨在探讨VEGF家族在转移性乳腺癌患者中的预后价值。重点关注神经纤毛蛋白-1（NRP-1）和胎盘生长因子（PlGF）。
在一项II期一线贝伐单抗联合化疗试验中，对65例接受转移性HER2阴性乳腺癌治疗的患者的基线血浆样本进行VEGF家族8个成员的分析。根据每个VEGF家族成员的中位数将患者分为高、低两组。确定每个VEGF家族成员的无进展生存期（PFS）和总生存期（OS）。
血浆NRP-1和PlGF水平低的患者的OS长于水平高的患者[多变量校正风险比（HRs）分别为2.54（95%置信区间（CI）1.11 - 5.82，p = 0.02）和3.11（95% CI 1.30 - 7.47，p = 0.01）]。NRP-1和PlGF水平均低的患者的OS显著延长，HR为6.
