Prognostic Influence of Pre-Operative C-Reactive Protein in Node-Negative Breast Cancer Patients

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.

Pre-treatment serum alkaline phosphatase and lactate dehydrogenase as prognostic factors in triple negative breast cancer

“…In recent years, some studies have demonstrated the prognostic value of blood parameters and serum parameters, which are inexpensive, accurate, identified by easy method of detection and validated. Although underlying mechanism is unclear, increased pretreatment blood parameters and serum parameters have been confirmed to associate with prognosis of several cancers, such as neutrophil-to-lymphocyte ratio (NLR)17, 18, lymphocyte-to-monocyte ratio (LMR), monocyte count19, platelet-to-lymphocyte ratio (PLR)20, fibrinogen21 haptoglobin 22and C-reactive protein23. The serum levels of ALP and LDH are routine diagnostic tests in clinical laboratories.…”

C-Reactive Protein and Breast Cancer: New Insights from Old Molecule

“…But on gene expression analysis in a subgroup of 72 patients, they for first time highlighted no relation of circulating CRP with gene expression. Numerous epidemiological prospective studies proved CRP as a well-established independent prognostic marker in breast cancer [ 32 ]. Breast cancer survivors with the state of chronic inflammation are at risk of recurrence of the disease as well as metabolic disturbances and CVD.…”

Prognostic impact of interleukin‑6 and C‑reactive protein on patients with breast cancer

“…Although the prognostic impact of preoperative CRP has been reported (16,17), other studies have described controversial results (18)(19)(20). Thus, the present study aimed to evaluate the prognostic impact of preoperative CRP and IL-6 expression levels in patients with breast cancer.…”

“…CRP, which was named for its capacity to precipitate C-polysaccharide of Streptococcus pneumoniae, is a sensitive and widely used inflammatory marker produced primarily in the liver, in response to IL-1, IL-6, tumor necrosis factor-α and IL-17 (7,8). CRP was reported to be associated with poor prognosis in nasopharyngeal (9), hepatocellular (10), pancreatic (11), colorectal (12), renal (13), urothelial (14) and prostate cancer (15), in addition to breast cancer (16,17). However, the association between CRP and the prognosis of patients with breast cancer remains controversial (18)(19)(20).…”