Rochefort Pauline, Chabaud Sylvie, Pierga Jean-Yves, Tredan Olivier, Brain Etienne, Bidard François-Clément, Schiffler Camille, Polena Helena, Khalil-Mgharbel Abir, Vilgrain Isabelle, Bachelot Thomas
Department of Medical Oncology, Centre Léon Bérard, 28 Rue Laennec, Lyon F-69373, France.
Direction de la Recherche Clinique et de l'Innovation, Centre Léon Bérard, Lyon F-69373, France.
Br J Cancer. 2017 Jan;116(3):356-361. doi: 10.1038/bjc.2016.427. Epub 2017 Jan 5.
Patients with metastatic breast cancer (MBC) represent a heterogeneous group, with large differences in outcomes from individual patients. VE-cadherin, an endothelial-specific cadherin, was shown to promote tumour proliferation and angiogenesis. Soluble VE-cadherin has been recently associated to breast cancer progression. This study was designed to investigate the prognosis significance of soluble VE-cadherin in hormone-refractory MBC.
Between 2004 and 2007, 150 patients with a fully documented history of hormone-refractory MBC were included in the prospective SEMTOF study. Serum concentrations of VE-cadherin were measured at inclusion for 141 patients and 6 weeks after the beginning of chemotherapy, using a sandwich enzyme immunoassay.
The presence of high levels of serum VE-cadherin was significantly correlated to a shorter progression-free (PFS) and overall survival (OS). In a multivariate analysis along with clinical and biologic prognostic parameters, high serum VE-cadherin level was an independent adverse prognostic variable for PFS (median PFS 9.7 (IC95: 8; 11.9) vs 5.8 (IC95: 4.1; 8) months P=0.0008) and OS (median OS 34 (IC95: 26.6; 47.1) vs 14.8 (IC95: 9.3; 21.4) months P=0.0007). Moreover, VE-cadherin decrease during chemotherapy was also associated with good prognosis.
Serum VE-cadherin levels correlate to poorer survival in patients with hormone-refractory MBC. As sVE-cadherin reflects tumour angiogenesis, this could have therapeutic implications for antiangiogenic treatment.
转移性乳腺癌(MBC)患者是一个异质性群体,个体患者的预后差异很大。血管内皮钙黏蛋白(VE-钙黏蛋白)是一种内皮细胞特异性钙黏蛋白,已被证明可促进肿瘤增殖和血管生成。可溶性VE-钙黏蛋白最近与乳腺癌进展相关。本研究旨在探讨可溶性VE-钙黏蛋白在激素难治性MBC中的预后意义。
在2004年至2007年期间,前瞻性SEMTOF研究纳入了150例有完整激素难治性MBC病史记录的患者。使用夹心酶免疫测定法,对141例患者入组时及化疗开始6周后的血清VE-钙黏蛋白浓度进行了测量。
血清VE-钙黏蛋白水平高与无进展生存期(PFS)和总生存期(OS)较短显著相关。在一项结合临床和生物学预后参数的多变量分析中,高血清VE-钙黏蛋白水平是PFS(中位PFS 9.7(95%置信区间:8;11.9)个月对5.8(95%置信区间:4.1;8)个月,P = 0.0008)和OS(中位OS 34(95%置信区间:26.6;47.1)个月对14.8(95%置信区间:9.3;21.4)个月,P = 0.0007)的独立不良预后变量。此外,化疗期间VE-钙黏蛋白水平下降也与良好预后相关。
血清VE-钙黏蛋白水平与激素难治性MBC患者的较差生存率相关。由于可溶性VE-钙黏蛋白反映肿瘤血管生成,这可能对抗血管生成治疗具有治疗意义。