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

Int J Cancer. 2002 Jan 20;97(3):278-82. doi: 10.1002/ijc.1610.


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 mdr1, 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-glycoprotein. In our pilot study, we analyzed the clinical relevance of YB-1 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Breast / metabolism
  • Breast Neoplasms / drug therapy
  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / surgery
  • CCAAT-Enhancer-Binding Proteins / metabolism*
  • CCAAT-Enhancer-Binding Proteins / physiology*
  • Cell Division
  • DNA-Binding Proteins*
  • Disease-Free Survival
  • Drug Resistance, Multiple
  • Drug Resistance, Neoplasm*
  • Female
  • Humans
  • Immunohistochemistry
  • Menopause
  • Middle Aged
  • NFI Transcription Factors
  • Neoplasm Metastasis
  • Nuclear Proteins
  • Phenotype
  • Plasminogen Activator Inhibitor 1 / metabolism*
  • Postmenopause
  • Premenopause
  • Receptor, ErbB-2 / metabolism*
  • Time Factors
  • Transcription Factors*
  • Urokinase-Type Plasminogen Activator / metabolism*
  • Y-Box-Binding Protein 1


  • CCAAT-Enhancer-Binding Proteins
  • DNA-Binding Proteins
  • NFI Transcription Factors
  • Nuclear Proteins
  • Plasminogen Activator Inhibitor 1
  • Transcription Factors
  • Y-Box-Binding Protein 1
  • YBX1 protein, human
  • Receptor, ErbB-2
  • Urokinase-Type Plasminogen Activator