p27Kip1 is a predictive factor for tamoxifen treatment response but not a prognostic marker in premenopausal breast cancer patients

Authors

  • Maria Stendahl,

    1. Center for Molecular Pathology, Lund University, Malmö University Hospital, Malmö, Sweden
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  • Sofie Nilsson,

    1. Center for Molecular Pathology, Lund University, Malmö University Hospital, Malmö, Sweden
    2. Breakthrough Breast Cancer Research Unit, School of Cancer, Enabling Sciences and Technology, University of Manchester, Manchester Academic Health Science Centre, Paterson Institute for Cancer Research, The Christie NHS Foundation Trust, Manchester, United Kingdom
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  • Caroline Wigerup,

    1. Center for Molecular Pathology, Lund University, Malmö University Hospital, Malmö, Sweden
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  • Karin Jirström,

    1. Center for Molecular Pathology, Lund University, Malmö University Hospital, Malmö, Sweden
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  • Per Ebbe Jönsson,

    1. Department of Surgery, Helsingborgs Lasarett, Helsingborg, Sweden
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  • Olle Stål,

    1. Division of Oncology, Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden
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  • Göran Landberg

    Corresponding author
    1. Center for Molecular Pathology, Lund University, Malmö University Hospital, Malmö, Sweden
    2. Breakthrough Breast Cancer Research Unit, School of Cancer, Enabling Sciences and Technology, University of Manchester, Manchester Academic Health Science Centre, Paterson Institute for Cancer Research, The Christie NHS Foundation Trust, Manchester, United Kingdom
    • Breakthrough Breast Cancer Research Unit, School of Cancer, Enabling Sciences and Technology, University of Manchester, Manchester Academic Health Science Centre, Paterson Institute for Cancer Research, The Christie NHS Foundation Trust, Wilmslow Road, Manchester, M20 4BX, UK
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    • Tel.: +44 1619187041


Abstract

The cell-cycle regulating protein p27Kip1 (p27) has dual roles by acting as both a cdk inhibitor and as an assembly factor for different cdk complexes. Loss of p27 has been linked to malignant features in tumours; however, the exact role of p27 deregulation in breast cancer regarding prognostic and treatment predictive information has not been fully clarified. We have evaluated p27 expression in 328 primary, Stage II breast cancers from premenopausal patients who had been randomised to either tamoxifen treatment or no adjuvant treatment after surgery. p27 was associated with the oestrogen receptor and cyclin D1, and p27 downregulation was associated with high proliferation. There was no association between recurrence-free survival (RFS) and p27 (HR = 0.800, 95% CI 0.523–1.222, p = 0.300), indicating that p27 is not a prognostic marker. The predictive value of p27 was analysed by comparing RFS in tamoxifen-treated and untreated patients in subgroups of low and high p27 expression (HR = 0.747, 95% CI 0.335–1.664, p = 0.474 and HR = 0.401, 95% CI 0.240–0.670, p < 0.001, respectively). Only patients with p27-high tumours benefited from tamoxifen (multivariate interaction analysis p = 0.034). Our study suggests that p27 downregulation is associated with tamoxifen resistance in premenopausal breast cancer but is not linked to impaired prognosis.

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