Tumor Microenvironment of Metastasis and Risk of Distant Metastasis of Breast Cancer
Tumor Microenvironment of Metastasis and Risk of Distant Metastasis of Breast Cancer
复制标题
DOI：
10.1093/jnci/dju136
复制
发表时间：
2014-08-01
影响因子：
10.3
通讯作者：
Jones, Joan G.
中科院分区：
文献类型：
--
作者：
Rohan, Thomas E.;Xue, Xiaonan;Jones, Joan G.
背景肿瘤转移微环境（TMEM）由巨噬细胞、内皮细胞和肿瘤细胞之间的直接接触组成，与啮齿动物乳腺肿瘤和人类乳腺癌的转移有关。方法采用病例对照研究的方法，对1980 ~ 2000年确诊的3760例浸润性导管乳腺癌患者进行随访，并对TMEM评分与IHC 4评分的相关性进行比较。病例患者为随后发生远处转移的女性;对照组受试者在初次诊断时的年龄和日历年匹配（1：1）。通过三重免疫染色评估TMEM，通过标准方法评估IHC 4;由对结果不知情的病理学家读取切片。使用逻辑回归估计比值比（OR）和95%置信区间（CI），并对临床变量进行调整。进行受试者操作特征分析，并估计曲线下面积。结果TMEM评分与雌激素受体（ER）（+）/人表皮生长因子受体（HER 2）-肿瘤远处转移风险增加相关（多变量OR（高与低三分位数）= 2.70; 95% CI = 1.39至5.26; P趋势= 0.004），而IHC 4评分具有临界正相关性（OR 10单位增加= 1.06; 95% CI = 1.00 - 1.13）;调整IHC 4评分后，TMEM评分的相关性持续存在。经临床变量调整后，TMEM的曲线下面积为0.78。结论TMEM评分预测ER+/HER 2-乳腺癌远处转移风险独立于IHC 4评分和经典临床病理特征。
Background Tumor microenvironment of metastasis (TMEM), consisting of direct contact between a macrophage, an endothelial cell, and a tumor cell, has been associated with metastasis in both rodent mammary tumors and human breast cancer. We prospectively examined the association between TMEM score and risk of distant metastasis and compared risk associated with TMEM score with that associated with IHC4.Methods We conducted a case-control study nested within a cohort of 3760 patients with invasive ductal breast carcinoma diagnosed between 1980 and 2000 and followed through 2010. Case patients were women who developed a subsequent distant metastasis; control subjects were matched (1: 1) on age at and calendar year of primary diagnosis. TMEM was assessed by triple immunostain and IHC4 by standard methods; slides were read by pathologists blinded to outcome. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using logistic regression, adjusted for clinical variables. A Receiver Operating Characteristic analysis was performed, and the area under the curve was estimated. All statistical tests were two-sided.Results TMEM score was associated with increased risk of distant metastasis in estrogen receptor (ER)(+)/human epidermal growth factor receptor (HER2)-tumors (multivariable OR (high vs low tertile) = 2.70; 95% CI = 1.39 to 5.26; P-trend = .004), whereas IHC4 score had a borderline positive association (OR10 unit increase = 1.06; 95% CI = 1.00 to 1.13); the association for TMEM score persisted after adjustment for IHC4 score. The area under the curve for TMEM, adjusted for clinical variables, was 0.78. Neither TMEM score nor IHC4 score was independently associated with metastatic risk overall or in the triple negative or HER2(+) subgroups.Conclusions TMEM score predicted risk of distant metastasis in ER+/HER2-breast cancer independently of IHC4 score and classical clinicopathologic features.