Item Type: | Article |
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Title: | Y-box factor YB-1 predicts drug resistance and patient outcome in breast cancer independent of clinically relevant tumor biologic factors HER2, uPA and PAI-1 |
Creators Name: | Janz, M., Harbeck, N., Dettmar, P., Berger, U., Schmidt, A., Juerchott, K., Schmitt, M. and Royer, H.D. |
Abstract: | Intrinsic or acquired resistance to chemotherapy is responsible for failure of current treatment regimens in breast cancer patients. The Y-box protein YB-1 regulates expression of the P-glycoprotein gene mdrl, which plays a major role in the development of a multidrug-resistant tumor phenotype. In human breast cancer, overexpression and nuclear localization of YB-1 is associated with upregulation of P-glycoprorein. In our pilot study, we analyzed the clinical relevance of YB-I expression in breast cancer (n = 83) after a median follow-up of 61 months and compared it with tumor-biologic factors already used for clinical risk-group discrimination, i.e., HER2, urokinase-type plasminogen activator (uPA) and plasminogen activator inhibitor type 1 (PAI-1). High YB-1 expression in tumor tissue and surrounding benign breast epithelial cells was significantly associated with poor patient outcome. In patients who received postoperative chemotherapy, the 5-year relapse rate was 66% in patients with high YB-1 expression. In contrast, in patients with low YB-1 expressions, no relapse has been observed so far. YB-1 expression thus indicates clinical drug resistance in breast cancer. Moreover, YB-1 correlates with breast cancer aggressiveness: in patients not treated with postoperative chemotherapy, those with low YB-1 expression are still free of disease, whereas the 5-year relapse rate in those with high YB-1 was 30%. There was no significant correlation between YB-1 expression and either HER2 expression or uPA and PAI-1 levels. Risk-group assessment achieved by YB-1 differed significantly from that by HER2 or uPA/PAI-1. In conclusion, YB-1 demonstrated prognostic and predictive significance in breast cancer by identifying high-risk patients in both the presence and absence of postoperative chemotherapy, independent of tumor-biologic factors currently available for clinical decision making. |
Keywords: | Breast Cancer, Drug Resistance, HER2, PAI-1, Prognosis, UPA, YB-1 |
Source: | International Journal of Cancer |
ISSN: | 0020-7136 |
Publisher: | Wiley |
Volume: | 97 |
Number: | 3 |
Page Range: | 278-282 |
Date: | 1 January 2002 |
Official Publication: | https://doi.org/10.1002/ijc.1610 |
PubMed: | View item in PubMed |
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