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.

• Authors: Lambert C J Dorssers, Nicolai Grebenchtchikov, Arend Brinkman, Maxime P Look, Simone P J van Broekhoven, Danielle de Jong, Harry A Peters, Henk Portengen, Marion E Meijer-van Gelder, Jan G M Klijn, Doorlene T H van Tienoven, Anneke Geurts-Moespot, Paul N Span, John A Foekens, Fred C G J Sweep
• Journal: Clinical cancer research : an official journal of the American Association for Cancer Research (Clin Cancer Res) Vol. 10 Issue 18 Pt 1 Pg. 6194-202 (Sep 15 2004) ISSN: 1078-0432 [Print] United States
• PMID: 15448007 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• BCAR1 protein, human
• Crk-Associated Substrate Protein
• Plasminogen Activator Inhibitor 1
• Proteins
• Retinoblastoma-Like Protein p130
• Urokinase-Type Plasminogen Activator

Topics

• 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
• Retinoblastoma-Like Protein p130
• Urokinase-Type Plasminogen Activator (metabolism)