title: Plasma fibrin D-dimer levels correlate with tumour volume, progression rate and survival in patients with metastatic breast cancer.
abstract: Plasma levels of D-dimer are elevated in cancer patients. Activation of the extrinsic coagulation system and the fibrinolytic cascade within a tumour is thought to be related with growth, invasion and metastasis. We have investigated the relationship between these markers of fibrin metabolism, standard clinicopathological variables and serum levels of angiogenic cytokines in three cohorts: group A (n=30) consisted of 30 healthy female volunteers, group B (n=23) of consecutive patients with operable breast cancer and group C (n=84) of patients with untreated or progressive metastatic breast cancer. Plasma D-dimers, fibrinogen, IL-6, vascular endothelial growth factor and calculated vascular endothelial growth factor load in platelets are clearly increased in patients with breast cancer. D-dimers were increased in nearly 89% of patients with progressive metastatic disease. The level of D-dimers was positively correlated with tumour load (P<0.0001), number of metastatic sites (P=0.002), progression kinetics (P<0.0001) and the cytokines related to angiogenesis: serum vascular endothelial growth factor (P=0.0016, Spearman correlation=0.285), calculated vascular endothelial growth factor load in platelets (P<0.0001, Spearman correlation=0.37) and serum interleukin-6 (P<0.0001, Spearman correlation=0.59). Similarly increased D-dimer levels were positively correlated with increased fibrinogen levels (P<0.0001, Spearman correlation=0.38). The association between markers of fibrin degradation in patients with progressive breast cancer suggests that the D-dimer level is a clinically important marker for progression and points towards a relation between haemostasis and tumour progression. A role of interleukin-6, by influencing both angiogenesis and haemostasis, is suggested by these observations.
authors.affiliation: Oncology Center, AZ St-Augustinus Oosterveldlaan 24, 2610 Wilrijk, Belgium. luc.dirix@pandora.be
authors.forename: Luc Y
authors.initials: LY
authors.lastname: Dirix
authors.forename: R
authors.initials: R
authors.lastname: Salgado
authors.forename: R
authors.initials: R
authors.lastname: Weytjens
authors.forename: C
authors.initials: C
authors.lastname: Colpaert
authors.forename: I
authors.initials: I
authors.lastname: Benoy
authors.forename: P
authors.initials: P
authors.lastname: Huget
authors.forename: P
authors.initials: P
authors.lastname: van Dam
authors.forename: A
authors.initials: A
authors.lastname: Prové
authors.forename: J
authors.initials: J
authors.lastname: Lemmens
authors.forename: P
authors.initials: P
authors.lastname: Vermeulen
mesh_terms: D000933:Antifibrinolytic Agents / Q000097:blood; D014408:Biomarkers, Tumor / Q000097:blood*; D001780:Blood Coagulation Tests; D001943:Breast Neoplasms / Q000097:blood / Q000401:mortality / Q000473:pathology*; D018450:Disease Progression; D018572:Disease-Free Survival; D005260:Female; D005338:Fibrin Fibrinogen Degradation Products / Q000032:analysis*; D006801:Humans; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging
chemical_list: D000933:Antifibrinolytic Agents; D014408:Biomarkers, Tumor; D005338:Fibrin Fibrinogen Degradation Products; C036309:fibrin fragment D