The prognostic value of BCAR1 in patients with primary breast cancer.
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.
|Keywords||Adult, Aged, Breast Neoplasms/diagnosis/*genetics/metabolism, Cell Line, Tumor, Cell Proliferation, Chemotherapy, Adjuvant, Crk-Associated Substrate Protein, Cytosol/metabolism, Disease-Free Survival, Enzyme-Linked Immunosorbent Assay, Female, Humans, Likelihood Functions, Middle aged, Multivariate Analysis, Plasminogen Activator Inhibitor 1/metabolism, Prognosis, Proportional Hazards Models, Proteins/*genetics, Recurrence, Research Support, Non-U.S. Gov't, Retinoblastoma-Like Protein p130, Urinary Plasminogen Activator/metabolism|
|Persistent URL||dx.doi.org/10.1158/1078-0432.CCR-04-0444, hdl.handle.net/1765/13506|
Dorssers, L.C.J., Grebenchtchikov, N., Brinkman, A., Look, M.P., Broekhoven, S.P., de Jong, D., … Sweep, F.C.. (2004). The prognostic value of BCAR1 in patients with primary breast cancer.. Clinical Cancer Research, 10(18 I), 6194–6202. doi:10.1158/1078-0432.CCR-04-0444