Prognostic influence of pre-operative C-reactive protein in node-negative breast cancer patients

PLoS One. 2014 Oct 23;9(10):e111306. doi: 10.1371/journal.pone.0111306. eCollection 2014.

Abstract

The importance of inflammation is increasingly noticed in cancer. The aim of this study was to analyze the prognostic influence of pre-operative serum C-reactive protein (CRP) in a cohort of 148 lymph node-negative breast cancer patients. The prognostic significance of CRP level for disease-free survival (DFS), metastasis-free survival (MFS) and overall survival (OS) was evaluated using univariate and multivariate Cox regression, also including information on age at diagnosis, tumor size, tumor grade, estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) status, proliferation index (Ki67) and molecular subtype, as well as an assessment of the presence of necrosis and inflammation in the tumor tissue. Univariate analysis showed that CRP, as a continuous variable, was significantly associated with DFS (P = 0.002, hazard ratio [HR] = 1.04, 95% confidence interval [CI] = 1.02-1.07) and OS (P = 0.036, HR= 1.03, 95% CI = 1.00-1.06), whereas a trend was observed for MFS (P = 0.111). In the multivariate analysis, CRP retained its significance for DFS (P = 0.033, HR= 1.01, 95% CI = 1.00-1.07) as well as OS (P = 0.023, HR= 1.03, 95% CI = 1.00-1.06), independent of established prognostic factors. Furthermore, large-scale gene expression analysis by Affymetrix HG-U133A arrays was performed for 72 (48.6%) patients. The correlations between serum CRP and gene expression levels in the corresponding carcinoma of the breast were assessed using Spearman's rank correlation, controlled for false-discovery rate. No significant correlation was observed between CRP level and gene expression indicative of an ongoing local inflammatory process. In summary, pre-operatively elevated CRP levels at the time of diagnosis were associated with shorter DFS and OS independent of established prognostic factors in node-negative breast cancer, supporting a possible link between inflammation and prognosis in breast cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Breast Neoplasms / blood*
  • Breast Neoplasms / mortality
  • Breast Neoplasms / surgery
  • C-Reactive Protein / metabolism*
  • Cell Proliferation
  • Cohort Studies
  • Disease-Free Survival
  • Female
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic
  • Genome, Human
  • Humans
  • Inflammation / metabolism
  • Ki-67 Antigen / metabolism
  • Lymph Nodes / pathology*
  • Middle Aged
  • Neoplasm Metastasis
  • Prognosis
  • Proportional Hazards Models
  • Receptor, ErbB-2 / metabolism
  • Receptors, Estrogen / metabolism
  • Receptors, Progesterone / metabolism

Substances

  • Ki-67 Antigen
  • Receptors, Estrogen
  • Receptors, Progesterone
  • C-Reactive Protein
  • ERBB2 protein, human
  • Receptor, ErbB-2

Grant support

This work was supported by the Federal Ministry of Education and Research (BMBF, NGFN project Oncoprofile). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.