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- Title
Bcar1/p130Cas protein and primary breast cancer: prognosis and response to tamoxifen treatment.
- Authors
van der Flier, Silvia; Brinkman, Arend; Look, Maxime P.; Kok, Elisabath M.; Meijer-van Gelder, Marion E.; Klijn, Jan G. M.; Dorssers, Lambert C. J.; Foekens, John A.; van der Flier, S; Brinkman, A; Look, M P; Kok, E M; Meijer-van Gelder, M E; Klijn, J G; Dorssers, L C; Foekens, J A
- Abstract
<bold>Background: </bold>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.<bold>Methods: </bold>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).<bold>Results: </bold>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.<bold>Conclusion: </bold>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.
- Subjects
BREAST cancer; TAMOXIFEN; DRUG therapy
- Publication
JNCI: Journal of the National Cancer Institute, 2000, Vol 92, Issue 2, p120
- ISSN
0027-8874
- Publication type
journal article
- DOI
10.1093/jnci/92.2.120