Elevated Biomarkers of Inflammation Are Associated With Reduced Survival Among Breast Cancer Patients
Elevated Biomarkers of Inflammation Are Associated With Reduced Survival Among Breast Cancer Patients
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DOI：
10.1200/jco.2008.18.9068
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发表时间：
2009-07-20
影响因子：
45.3
通讯作者：
Ulrich, Cornelia M.
中科院分区：
文献类型：
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作者：
Pierce, Brandon L.;Ballard-Barbash, Rachel;Ulrich, Cornelia M.
目的慢性炎症被认为有助于乳腺癌的发生和发展。系统性C-反应蛋白（CRP）和血清淀粉样蛋白A（SAA）的措施，低度慢性炎症和潜在的预测癌症survival.Patients和方法我们评估了炎症和乳腺癌生存的循环标志物之间的关系，从健康，饮食，活动和生活方式（HEAL）研究（一个多种族的前瞻性队列研究，诊断为0至IIIA期乳腺癌的妇女）的数据。在诊断后约31个月测量了CRP和SAA的循环浓度，并在734名无病乳腺癌幸存者中测试了其与无病生存期（约4.1年随访）和总生存期（约6.9年随访）的相关性。考克斯比例风险模型用于调整潜在的混杂因素，以产生风险比（HR）和95%CIs.Results SAA和CRP升高与总生存率降低相关，无论调整年龄，肿瘤分期，种族和体重指数（SAA P趋势<0.0001; CRP P趋势= 0.002）。SAA和CRP三分位数的HR表明对生存期存在阈值效应，而非剂量-反应关系（最高vs最低三分位数：SAA HR = 3.15; 95% CI，1.73 - 5.65; CRP HR = 2.27; 95% CI，1.27 - 4.08）。相关性相似，在调整了自我报告的心血管事件史和审查心血管疾病死亡后仍然显著。CRP和SAA升高也与无病生存率降低相关，尽管这些相关性具有边缘意义（SAA P趋势= .04; CRP P趋势= .07）。结论循环SAA和CRP可能是乳腺癌患者长期生存的重要预后标志物，与种族、肿瘤分期和体重指数无关。
Purpose Chronic inflammation is believed to contribute to the development and progression of breast cancer. Systemic C-reactive protein (CRP) and serum amyloid A (SAA) are measures of low-grade chronic inflammation and potential predictors of cancer survival.Patients and Methods We evaluated the relationship between circulating markers of inflammation and breast cancer survival using data from the Health, Eating, Activity, and Lifestyle (HEAL) Study (a multiethnic prospective cohort study of women diagnosed with stage 0 to IIIA breast cancer). Circulating concentrations of CRP and SAA were measured approximately 31 months after diagnosis and tested for associations with disease-free survival (approximately 4.1 years of follow-up) and overall survival (approximately 6.9 years of follow-up) in 734 disease-free breast cancer survivors. Cox proportional hazards models were used with adjustment for potential confounding factors to generate hazard ratios (HRs) and 95% CIs.Results Elevated SAA and CRP were associated with reduced overall survival, regardless of adjustment for age, tumor stage, race, and body mass index (SAA P trend < .0001; CRP P trend = .002). The HRs for SAA and CRP tertiles suggested a threshold effect on survival, rather than a dose-response relationship (highest v lowest tertile: SAA HR = 3.15; 95% CI, 1.73 to 5.65; CRP HR = 2.27; 95% CI, 1.27 to 4.08). Associations were similar and still significant after adjusting for self-reported history of cardiovascular events and censoring cardiovascular disease deaths. Elevated CRP and SAA were also associated with reduced disease-free survival, although these associations were of borderline significance (SAA P trend = .04; CRP P trend = .07).Conclusion Circulating SAA and CRP may be important prognostic markers for long-term survival in breast cancer patients, independent of race, tumor stage, and body mass index.