Servicio de Hematología y Oncología Médica, Hospital Universitario Morales Meseguer, Avda. Marqués de los Velez, s/n, 30008, Murcia, Spain.
Instituto Murciano de Investigación Biosanitaria (IMIB-Arrixaca), Murcia, Spain.
Breast Cancer Res Treat. 2018 May;169(1):83-92. doi: 10.1007/s10549-017-4656-z. Epub 2018 Jan 16.
Therapeutic exploitation of angiogenesis in breast cancer has been limited by the lack of reliable biomarkers. Circulating small-sized endothelial microparticles (sEMP) are likely to play a significant role as messengers of angiogenesis. Higher levels of EMP have been observed in cancer patients, but their prognostic value in breast cancer is unknown. Our aim was to determine the value of circulating sEMP as a marker of response to chemotherapy in breast cancer.
We included patients with breast cancer treated with neoadjuvant or first-line chemotherapy. Baseline and post-treatment circulating sEMP (CD144+) were quantified using a flow cytometer approach specifically designed for analysis of small-sized particles (0.1-0.5 μm). Small-sized EMP response was defined as a post-treatment decrease of sEMP larger than the median decrease of sEMP after chemotherapy. Baseline and post-chemotherapy VEGFA levels were determined with ELISA.
Forty-four breast cancer patients were included (19 with metastatic and 25 with locally advanced disease). Median levels of sEMP decreased after chemotherapy (P = 0.005). Response to chemotherapy showed a non-significant trend to associate with sEMP response (P = 0.056). A sEMP response was observed in 51% of patients and was associated with better overall survival (HR 0.18; 95% CI 0.04-0.87; P = 0.02) and progression free survival (HR 0.30; 95% CI 0.09-0.99; P = 0.04) in the group of women with metastatic disease. Post-chemotherapy decrease of VEGFA levels was not associated with breast cancer prognosis.
Our results did not support sEMP as a marker of response to chemotherapy. However, our exploratory analysis suggests that in patients with metastatic breast cancer, the decrease of sEMP levels after chemotherapy is associated with better overall and disease free survival and might be superior to VEGFA levels as an angiogenesis-related prognostic marker.
在乳腺癌中，血管生成的治疗利用受到缺乏可靠生物标志物的限制。循环中小型内皮细胞微颗粒（sEMP）可能作为血管生成的信使发挥重要作用。在癌症患者中观察到更高水平的 EMP，但它们在乳腺癌中的预后价值尚不清楚。我们的目的是确定循环 sEMP 作为乳腺癌对化疗反应的标志物的价值。
我们纳入了接受新辅助或一线化疗的乳腺癌患者。使用专门设计用于分析 0.1-0.5μm 小颗粒的流式细胞仪方法定量检测基线和治疗后循环 sEMP（CD144+）。将 sEMP 的小尺寸反应定义为治疗后 sEMP 的减少大于化疗后 sEMP 中位数减少。使用 ELISA 测定基线和化疗后 VEGFA 水平。
共纳入 44 例乳腺癌患者（转移性 19 例，局部晚期 25 例）。化疗后 sEMP 水平中位数降低（P=0.005）。化疗反应与 sEMP 反应呈非显著趋势相关（P=0.056）。在 51%的患者中观察到 sEMP 反应，与转移性疾病女性的总生存期（HR 0.18；95%CI 0.04-0.87；P=0.02）和无进展生存期（HR 0.30；95%CI 0.09-0.99；P=0.04）更好相关。化疗后 VEGFA 水平的降低与乳腺癌预后无关。
我们的结果不支持 sEMP 作为化疗反应的标志物。然而，我们的探索性分析表明，在转移性乳腺癌患者中，化疗后 sEMP 水平的降低与更好的总生存期和无病生存期相关，并且可能优于 VEGFA 水平作为与血管生成相关的预后标志物。
