Circulating small-sized endothelial microparticles as predictors of clinical outcome after chemotherapy for breast cancer: an exploratory analysis
Circulating small-sized endothelial microparticles as predictors of clinical outcome after chemotherapy for breast cancer: an exploratory analysis
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DOI：
10.1007/s10549-017-4656-z
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发表时间：
2018-05-01
影响因子：
3.8
通讯作者：
Ayala de la Pena, Francisco
中科院分区：
文献类型：
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作者：
Garcia Garre, Elisa;Luengo Gil, Gines;Ayala de la Pena, Francisco
由于缺乏可靠的生物标志物，乳腺癌血管生成的治疗利用受到限制。循环小尺寸内皮微粒（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较高水平的 EMP，但其对乳腺癌的预后价值尚不清楚。我们的目的是确定循环 sEMP 作为乳腺癌化疗反应标志物的价值。我们纳入了接受新辅助或一线化疗治疗的乳腺癌患者。使用专为分析小尺寸颗粒（0.1-0.5μm）而设计的流式细胞仪方法对基线和治疗后循环 sEMP（CD144+）进行定量。小规模 EMP 反应定义为治疗后 sEMP 下降幅度大于化疗后 sEMP 下降中位数。采用 ELISA 测定基线和化疗后 VEGFA 水平。纳入了 44 名乳腺癌患者（19 名患有转移性乳腺癌，25 名患有局部晚期疾病）。化疗后 sEMP 的中位水平下降（P = 0.005）。化疗反应与 sEMP 反应无显着相关趋势 (P = 0.056)。在 51% 的患者中观察到 sEMP 反应，并且与转移性疾病女性组中更好的总生存期（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）相关。化疗后 VEGFA 水平下降与乳腺癌预后无关。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体生存率和无病生存率相关，并且作为血管生成相关的预后标志物可能优于 VEGFA 水平。
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 mu m). 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.