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.
PURPOSE:BCAR1, the human homologue of the ratp130Cas protein, was identified in a functional screen for humanbreast 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.
Authors: Yingchun Wang; Jonathan A Kelber; Hop S Tran Cao; Greg T Cantin; Rui Lin; Wei Wang; Sharmeela Kaushal; Jeanne M Bristow; Thomas S Edgington; Robert M Hoffman; Michael Bouvet; John R Yates; Richard L Klemke Journal: Proc Natl Acad Sci U S A Date: 2010-06-01 Impact factor: 11.205
Authors: Alpa M Nick; Rebecca L Stone; Guillermo Armaiz-Pena; Bulent Ozpolat; Ibrahim Tekedereli; Whitney S Graybill; Charles N Landen; Gabriel Villares; Pablo Vivas-Mejia; Justin Bottsford-Miller; Hye Sun Kim; Ju-Seog Lee; Soo Mi Kim; Keith A Baggerly; Prahlad T Ram; Michael T Deavers; Robert L Coleman; Gabriel Lopez-Berestein; Anil K Sood Journal: J Natl Cancer Inst Date: 2011-09-28 Impact factor: 13.506
Authors: Pierre Vanden Borre; Richard I Near; Anthony Makkinje; Gustavo Mostoslavsky; Adam Lerner Journal: Cell Signal Date: 2011-01-22 Impact factor: 4.315