Serial plasma osteopontin levels have prognostic value in metastatic breast cancer
Serial plasma osteopontin levels have prognostic value in metastatic breast cancer
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DOI：
10.1158/1078-0432.ccr-05-2354
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发表时间：
2006-06-01
影响因子：
11.5
通讯作者：
Chambers, Ann F.
中科院分区：
文献类型：
--
作者：
Bramwell, Vivien H. C.;Doig, Gordon S.;Chambers, Ann F.
目的：骨桥蛋白是一种可在血液和肿瘤组织中检测到的恶性肿瘤相关蛋白。为了评估其在晚期疾病的预后价值，我们进行了一项前瞻性的临床研究，测量一系列的骨桥蛋白血浆水平的妇女转移性乳腺癌在整个病程的diseases.Experimental设计：一百五十八名妇女，新诊断的转移性乳腺癌被纳入这项研究。在基线和治疗期间和治疗后每3至12周，使用我们验证的ELISA测量血浆骨桥蛋白，直至死亡。多变量的时间依赖性生存分析进行了使用模型，右删失患者的结果3，6，和12个月后，最后一次已知的骨桥蛋白measurement.Results：骨桥蛋白测定1,378样本（中位数，9每例患者）。99例患者基线骨桥蛋白升高（中位数，177 ng/mL;范围，1- 2，648 ng/mL）。在单变量分析中，基线骨桥蛋白升高与生存期短相关（P = 0.02）。在纳入标准预后因素的多变量模型中，基线骨桥蛋白与生存期显著相关（相对危险度，1.001; P = 0.038）。无转移间期、内脏转移和东部肿瘤协作组状态2 - 4也保持显著性。在纳入标准预后因素和骨桥蛋白水平连续变化的多变量模型中，骨桥蛋白在任何时间>250 ng/mL的增加是对不良生存率具有最大预后价值的变量（相对危险度，3.26; P = 0.0003），东部肿瘤协作组的不良状态也保持了显著性。这是第一项研究表明，在转移性乳腺癌妇女中，骨桥蛋白水平随时间的增加与生存率低密切相关。骨桥蛋白的连续监测可能有助于这些患者的治疗决策。
Purpose: Osteopontin is a malignancy-associated protein measurable in blood and tumor tissue. To evaluate its prognostic value in advanced disease, we conducted a prospective clinical study measuring serial osteopontin plasma levels in women with metastatic breast cancer throughout the course of their disease.Experimental Design: One hundred fifty-eight women with,newly diagnosed metastatic breast cancer were enrolled in the study. Plasma osteopontin was measured using our validated ELISA, at baseline and every 3 to 12 weeks during and after therapy until death. Multivariate time-dependent survival analyses were conducted using models that right censored patient outcomes 3, 6, and 12 months after the last known osteopontin measurement.Results: Osteopontin was measured in 1,378 samples (median, 9 per patient). Ninety-nine patients had elevated baseline osteopontin (median, 177 ng/mL; range, 1-2,648 ng/mL). In univariate analysis, elevated baseline osteopontin was associated with short survival (P = 0.02). In a multivariate model incorporating standard prognostic factors, baseline osteopontin was significantly associated with survival duration (relative risk, 1.001; P = 0.038). Metastasis-free interval, visceral metastases, and Eastern Cooperative Oncology Group status 2 to 4 also retained significance. In a multivariate model incorporating standard prognostic factors and changes in sequential osteopontin levels, an osteopontin increase of >250 ng/mL at any time was the variable with the most prognostic value for poor survival (relative risk, 3.26; P = 0.0003), and poor Eastern Cooperative Oncology Group status also retained significance.Conclusions: This is the first study to show that in women with metastatic breast cancer, increases in osteopontin levels over time are strongly associated with poor survival. Sequential monitoring of osteopontin may have use in making treatment decisions for these patients.