title: 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.
authors.affiliation: Department of Obstetrics and Gynecology, Johannes Gutenberg University, Mainz, Germany.
authors.forename: Isabel
authors.initials: I
authors.lastname: Sicking
authors.affiliation: Leibniz Research Centre for Working Environment and Human Factors (IfADo), Dortmund University of Technology, Dortmund, Germany.
authors.forename: Karolina
authors.initials: K
authors.lastname: Edlund
authors.affiliation: Department of Obstetrics and Gynecology, Johannes Gutenberg University, Mainz, Germany.
authors.forename: Eva
authors.initials: E
authors.lastname: Wesbuer
authors.affiliation: Institute of Medical Biometry, Epidemiology and Informatics (IMBEI), Johannes Gutenberg University, Mainz, Germany.
authors.forename: Veronika
authors.initials: V
authors.lastname: Weyer
authors.affiliation: Department of Obstetrics and Gynecology, Johannes Gutenberg University, Mainz, Germany.
authors.forename: Marco J
authors.initials: MJ
authors.lastname: Battista
authors.affiliation: Department of Obstetrics and Gynecology, Johannes Gutenberg University, Mainz, Germany.
authors.forename: Antje
authors.initials: A
authors.lastname: Lebrecht
authors.affiliation: Department of Obstetrics and Gynecology, Johannes Gutenberg University, Mainz, Germany.
authors.forename: Christine
authors.initials: C
authors.lastname: Solbach
authors.affiliation: Department of Statistics, Dortmund University of Technology, Dortmund, Germany.
authors.forename: Marianna
authors.initials: M
authors.lastname: Grinberg
authors.affiliation: Institute for Clinical Chemistry, Johannes Gutenberg University, Mainz, Germany.
authors.forename: Johannes
authors.initials: J
authors.lastname: Lotz
authors.affiliation: Department of Obstetrics and Gynecology, Johannes Gutenberg University, Mainz, Germany.
authors.forename: Gerald
authors.initials: G
authors.lastname: Hoffmann
authors.affiliation: Department of Statistics, Dortmund University of Technology, Dortmund, Germany.
authors.forename: Jörg
authors.initials: J
authors.lastname: Rahnenführer
authors.affiliation: Leibniz Research Centre for Working Environment and Human Factors (IfADo), Dortmund University of Technology, Dortmund, Germany.
authors.forename: Jan G
authors.initials: JG
authors.lastname: Hengstler
authors.affiliation: Department of Obstetrics and Gynecology, Johannes Gutenberg University, Mainz, Germany.
authors.forename: Marcus
authors.initials: M
authors.lastname: Schmidt
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000097:blood* / Q000401:mortality / Q000601:surgery; D002097:C-Reactive Protein / Q000378:metabolism*; D049109:Cell Proliferation; D015331:Cohort Studies; D018572:Disease-Free Survival; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D015894:Genome, Human; D006801:Humans; D007249:Inflammation / Q000378:metabolism; D019394:Ki-67 Antigen / Q000378:metabolism; D008198:Lymph Nodes / Q000473:pathology*; D008875:Middle Aged; D009362:Neoplasm Metastasis; D011379:Prognosis; D016016:Proportional Hazards Models; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D011960:Receptors, Estrogen / Q000378:metabolism; D011980:Receptors, Progesterone / Q000378:metabolism
chemical_list: D002097:C-Reactive Protein; D019394:Ki-67 Antigen; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; C508053:ERBB2 protein, human