Bcar1/p130Cas protein and primary breast cancer: Prognosis and response totamoxifen treatment

Background: The product of the Bcar1/p130Cas (breast cancer resistance/p130 Crk-associated substrate) gene causes resistance to antiestrogen drugs in h uman breast cancer cells in vitro. To investigate its role in clinical brea st cancer, me determined the levels of Bcar1/p130Cas protein in a large ser ies of primary breast carcinomas. Methods: We measured Bcar1/p130Cas protei n in cytosol extracts from 937 primary breast carcinomas by western blot an alysis. The levels of Bcar1/p130Cas protein were tested for associations an d trends against clinicopathologic and patient characteristics, the lengths of relapse-free survival and overall survival (n = 775), and the efficacy of first-line treatment with tamoxifen for recurrent or metastatic disease (n = 268). Results: Bcar1/p130Cas levels in primary tumors were associated with age/menopausal status and the levels of estrogen receptor and progeste rone receptor. In univariate survival analysis, higher Bcar1/p130Cas levels were associated with poor relapse-free survival and overall survival (both two-sided P = .04; log-rank test for trend). In multivariate analysis, a h igh level of Bcar1/p130Cas was independently associated with poor relapse-f ree survival and overall survival. The response to tamoxifen therapy in pat ients with recurrent disease was reduced in patients with primary tumors th at expressed high levels of Bcar1/p130Cas. In multivariate analysis for res ponse, Bcar1/p130Cas was independent of classical predictive factors, such as estrogen receptor status, age/menopausal status, disease-free interval, and dominant site of relapse. Conclusion: Patients with primary breast tumo rs expressing a high level of Bcar1/p130Cas protein appear to experience mo re rapid disease recurrence and have a greater risk of (intrinsic) resistan ce to tamoxifen therapy. Thus, measurement of Bcar1/p139Cas may provide use ful prognostic information for patients with primary or metastatic breast c ancer.