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


CONCLUSIONS
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.
van der Flier
S
S
Department of Pathology/Division of Molecular Biology, Josephine Nefkens Institute, University Hospital Rotterdam, The Netherlands.
Brinkman
A
A
Look
M P
MP
Kok
E M
EM
Meijer-van Gelder
M E
ME
Klijn
J G
JG
Dorssers
L C
LC
Foekens
J A
JA
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology / Q000627:therapeutic use*; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism*; D050719:Crk-Associated Substrate Protein; D020847:Estrogen Receptor Modulators / Q000494:pharmacology / Q000627:therapeutic use*; D005260:Female; D019398:Genes, BRCA1 / Q000187:drug effects*; D006801:Humans; D016015:Logistic Models; D008875:Middle Aged; D009376:Neoplasms, Hormone-Dependent / Q000188:drug therapy* / Q000378:metabolism*; D010750:Phosphoproteins / Q000187:drug effects / Q000235:genetics*; D011379:Prognosis; D016016:Proportional Hazards Models; D011506:Proteins; D011960:Receptors, Estrogen / Q000187:drug effects; D011980:Receptors, Progesterone / Q000187:drug effects; D050717:Retinoblastoma-Like Protein p130; D016019:Survival Analysis; D013629:Tamoxifen / Q000494:pharmacology / Q000627:therapeutic use*; D016896:Treatment Outcome
D018931:Antineoplastic Agents, Hormonal; C493841:BCAR1 protein, human; D050719:Crk-Associated Substrate Protein; D020847:Estrogen Receptor Modulators; D010750:Phosphoproteins; D011506:Proteins; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D050717:Retinoblastoma-Like Protein p130; D013629:Tamoxifen