Bcar1/p130Cas protein and primary breast cancer: prognosis and response to tamoxifen treatment.

Abstract

BACKGROUND:

The product of the Bcar1/p130Cas (breast cancer resistance/p130Crk-associated substrate) gene causes resistance to antiestrogen drugs in human breast cancer cells in vitro. To investigate its role in clinical breast cancer, we determined the levels of Bcar1/p130Cas protein in a large series of primary breast carcinomas.

METHODS:

We measured Bcar1/p130Cas protein in cytosol extracts from 937 primary breast carcinomas by western blot analysis. The levels of Bcar1/p130Cas protein were tested for associations and 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 progesterone 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 high level of Bcar1/p130Cas was independently associated with poor relapse-free survival and overall survival. The response to tamoxifen therapy in patients with recurrent disease was reduced in patients with primary tumors that expressed high levels of Bcar1/p130Cas. In multivariate analysis for response, 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 tumors expressing a high level of Bcar1/p130Cas protein appear to experience more rapid disease recurrence and have a greater risk of (intrinsic) resistance to tamoxifen therapy. Thus, measurement of Bcar1/p130Cas may provide useful prognostic information for patients with primary or metastatic breast cancer.

• Authors: S van der Flier, A Brinkman, M P Look, E M Kok, M E Meijer-van Gelder, J G Klijn, L C Dorssers, J A Foekens
• Journal: Journal of the National Cancer Institute (J Natl Cancer Inst) Vol. 92 Issue 2 Pg. 120-7 (Jan 19 2000) ISSN: 0027-8874 [Print] United States
• PMID: 10639513 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents, Hormonal
• BCAR1 protein, human
• Crk-Associated Substrate Protein
• Estrogen Receptor Modulators
• Phosphoproteins
• Proteins
• Receptors, Estrogen
• Receptors, Progesterone
• Retinoblastoma-Like Protein p130
• Tamoxifen

Topics

• Adult
• Aged
• Aged, 80 and over
• Antineoplastic Agents, Hormonal (pharmacology, therapeutic use)
• Blotting, Western
• Breast Neoplasms (drug therapy, metabolism)
• Crk-Associated Substrate Protein
• Estrogen Receptor Modulators (pharmacology, therapeutic use)
• Female
• Genes, BRCA1 (drug effects)
• Humans
• Logistic Models
• Middle Aged
• Neoplasms, Hormone-Dependent (drug therapy, metabolism)
• Phosphoproteins (drug effects, genetics)
• Prognosis
• Proportional Hazards Models
• Proteins
• Receptors, Estrogen (drug effects)
• Receptors, Progesterone (drug effects)
• Retinoblastoma-Like Protein p130
• Survival Analysis
• Tamoxifen (pharmacology, therapeutic use)
• Treatment Outcome