Systematic review and meta-analysis of C-reactive protein as a biomarker in breast cancer

Inflammation is an enabling characteristic of the hallmarks of cancer. There has therefore been increasing interest in the clinical value of circulating inflammatory biomarkers in cancer. In this review, we summarize results on C-reactive protein (CRP), alone or as part of the Glasgow Prognostic Score (GPS, composed of CRP and serum albumin), as a biomarker of prognosis or prediction and monitoring of therapeutic response in patients with breast cancer. A systematic literature search was performed in Medline and Embase from 1990 to August 2021. The association of serum CRP and overall survival and disease/progression-free survival was summarized in meta-analyses using a random effects model. The results from a total of 35 included studies (20,936 patients) were divided according to three identified patient settings (metastatic, non-metastatic, and general setting). Most of the studies examined prognostic utility. Several larger studies observed associations between high serum CRP and poor survival, but the meta-analyses suggested a limited value in a non-metastatic and general breast cancer setting (populations with unknown or varied disease stage). In metastatic patients, however, more consistent findings supported an association between serum CRP and prognosis (hazard ratio for overall survival: 1.87 (95% CI 1.31–2.67). Only five studies examined a role in prediction or monitoring of therapeutic response. One study reported a significant association between serum CRP levels and response to chemotherapy. Findings regarding serum CRP as a biomarker in breast cancer appear inconsistent, particularly in non-metastatic and general breast cancer, where the prognostic value could not be confirmed. In patients with metastatic breast cancer we suggest that high serum CRP is an indicator of poor prognosis. Too few studies assessed the role of serum CRP in prediction or monitoring of treatment response to allow conclusions.

炎症是癌症标志性特征（hallmarks of cancer）的核心赋能特征。因此，学界对循环炎症生物标志物（circulating inflammatory biomarkers）在癌症中的临床价值的关注度与日俱增。本综述总结了C反应蛋白（C-reactive protein，CRP）单独应用，或作为格拉斯哥预后评分（Glasgow Prognostic Score，GPS，由CRP与血清白蛋白组成）的组成部分时，作为乳腺癌患者预后、治疗反应预测与监测生物标志物的相关研究结果。本研究于1990年至2021年8月间，在Medline与Embase数据库中开展了系统文献检索（systematic literature search）。采用随机效应模型（random effects model）进行荟萃分析（meta-analyses），总结了血清CRP与总生存期、无病/无进展生存期（disease/progression-free survival）之间的关联。纳入的35项研究（共20936例患者）的结果，按三类明确的患者场景进行划分：转移性乳腺癌、非转移性乳腺癌以及泛乳腺癌人群。多数研究考察了CRP的预后价值。多项大规模研究观察到血清CRP水平升高与不良生存期存在关联，但荟萃分析结果显示，在非转移性与泛乳腺癌人群（疾病分期未知或异质性较强的队列）中，CRP的预后价值有限。然而在转移性乳腺癌患者中，更为一致的研究结果支持血清CRP水平与预后存在关联（总生存期的风险比（hazard ratio）：1.87，95%置信区间1.31~2.67）。仅有5项研究考察了CRP在治疗反应预测或监测中的作用。其中一项研究报告称，血清CRP水平与化疗（chemotherapy）响应存在显著关联。现有关于血清CRP作为乳腺癌生物标志物的研究结果并不一致，在非转移性与泛乳腺癌人群中尤为如此，这类人群中CRP的预后价值尚未得到证实。对于转移性乳腺癌患者，我们认为血清CRP水平升高可作为不良预后的指示指标。目前考察血清CRP在治疗反应预测或监测中作用的研究数量过少，尚无法得出明确结论。