The Prognostic Value of BCAR1 in Patients with Primary Breast Cancer
The Prognostic Value of BCAR1 in Patients with Primary Breast Cancer
Abstract Purpose: BCAR1, the human homologue of the rat p130Cas protein, was identified in a functional screen for human breast cancer cell proliferation resistant to antiestrogen drugs. Here, we study the prognostic value of quantitative BCAR1 levels in a large series of breast cancer specimens. Experimental Design: A specific ELISA was developed to measure BCAR1 protein levels in 2593 primary breast tumor cytosols. Tumor levels of BCAR1 were correlated with relapse-free survival (RFS) and overall survival (OS) and compared with collected data on urokinase-type plasminogen activator (uPA) and plasminogen activator inhibitor 1 (PAI-1). Results: In tumor cytosols, BCAR1 protein levels varied between 0.02 and 23 ng/mg protein. BCAR1 levels exhibited a positive correlation with steroid hormone receptor levels, age and menopausal status, and uPA and PAI-1 levels. The level of BCAR1 (continuous or categorized as low, intermediate, or high) was inversely related with RFS and OS time. Multivariate analysis showed that BCAR1 levels contributed independently to a base model containing the traditional prognostic factors for both RFS and OS (both P < 0.0001). When added together with uPA and PAI-1 in the multivariate model, BCAR1 contributed independently of PAI-1 and was favored over uPA. Interaction tests allowed for additional analyses of BCAR1 protein levels in clinically relevant subgroups stratified by nodal and menopausal status. Conclusions: The quantitative BCAR1 protein level represents a prognostic factor for RFS and OS in primary breast cancer, independent of the traditional prognostic factors and the other novel marker PAI-1.
- Radboud University Nijmegen Medical Centre Netherlands
- Radboud University Nijmegen Netherlands
- Erasmus University Rotterdam Netherlands
Adult, Breast Neoplasms, Enzyme-Linked Immunosorbent Assay, Disease-Free Survival, Cytosol, SDG 3 - Good Health and Well-being, Recurrence, Cell Line, Tumor, Plasminogen Activator Inhibitor 1, Humans, UMCN 5.2: Endocrinology and reproduction, Aged, Cell Proliferation, Proportional Hazards Models, Likelihood Functions, Proteins, Middle Aged, Prognosis, EMC MM-03-24-07, Crk-Associated Substrate Protein, Chemotherapy, Adjuvant, Multivariate Analysis, Female, EMC MM-03-86-01
Adult, Breast Neoplasms, Enzyme-Linked Immunosorbent Assay, Disease-Free Survival, Cytosol, SDG 3 - Good Health and Well-being, Recurrence, Cell Line, Tumor, Plasminogen Activator Inhibitor 1, Humans, UMCN 5.2: Endocrinology and reproduction, Aged, Cell Proliferation, Proportional Hazards Models, Likelihood Functions, Proteins, Middle Aged, Prognosis, EMC MM-03-24-07, Crk-Associated Substrate Protein, Chemotherapy, Adjuvant, Multivariate Analysis, Female, EMC MM-03-86-01
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