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

Authors

  • Martin Janz,

    1. Department of Cell Growth and Differentiation, Max Delbrück Center for Molecular Medicine, Berlin, Germany
    2. Robert-Rössle-Klinik, Charité, Medizinische Fakultät der Humboldt-Universität, Berlin, Germany
    Search for more papers by this author
    • The first two authors contributed equally to this work.

  • Nadia Harbeck,

    1. Klinische Forschergruppe der Frauenklinik, Klinikum rechts der Isar, Technische Universität, München, Germany
    Search for more papers by this author
    • The first two authors contributed equally to this work.

  • Peer Dettmar,

    1. Institut für Allgemeine Pathologie und Pathologische Anatomie, Klinikum rechts der Isar, Technische Universität, München, Germany
    Search for more papers by this author
  • Ursula Berger,

    1. Institut für Medizinische Statistik und Epidemiologie, Technische Universität, München, Germany
    Search for more papers by this author
  • Anja Schmidt,

    1. Department of Cell Growth and Differentiation, Max Delbrück Center for Molecular Medicine, Berlin, Germany
    Search for more papers by this author
  • Karsten Jürchott,

    1. Department of Cell Growth and Differentiation, Max Delbrück Center for Molecular Medicine, Berlin, Germany
    Search for more papers by this author
  • Manfred Schmitt,

    1. Klinische Forschergruppe der Frauenklinik, Klinikum rechts der Isar, Technische Universität, München, Germany
    Search for more papers by this author
  • Hans-Dieter Royer

    Corresponding author
    1. Department of Cell Growth and Differentiation, Max Delbrück Center for Molecular Medicine, Berlin, Germany
    2. Institut für Transplantationsdiagnostik und Zelltherapeutika, Heinrich-Heine-Universität Düsseldorf, Germany
    • Institut für Transplantationsdiagnostik und Zelltherapeutika, Moorenstrasse 5, D-40225 Düsseldorf, Germany
    Search for more papers by this author
    • Fax: +49-211-811-9147


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 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. © 2001 Wiley-Liss, Inc.

Ancillary