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Cyclin E confers a prognostic value in premenopausal breast cancer patients with tumours exhibiting an infiltrative growth pattern
  1. P Berglund1,
  2. M Stighall1,
  3. K Jirström1,
  4. L Rydén2,
  5. M Fernö3,
  6. B Nordenskjöld4,
  7. G Landberg1
  1. 1
    Center for Molecular Pathology, Department of Laboratory Medicine, Lund University, Malmö University Hospital, Malmö, Sweden
  2. 2
    Department of Surgery, Helsingborg Hospital, Helsingborg, Sweden
  3. 3
    Department of Oncology, Lund University Hospital, Lund, Sweden
  4. 4
    Department of Oncology, Linköping University Hospital, Linköping, Sweden
  1. Dr Göran Landberg, Center for Molecular Pathology, Department of Laboratory Medicine, Lund University, Malmö University Hospital, SE-205 02 Malmö, Sweden; goran.landberg{at}


Aims: To investigate the prognostic value of cyclin E in relation to tumour growth pattern by analysing stage II primary breast cancers from premenopausal women not subjected to any further adjuvant treatment. To analyse the value of cyclin E as a predictor of tamoxifen response, by comparing untreated and treated patients with oestrogen receptor positive tumours.

Methods: Breast cancer samples, assembled in tissue microarrays, were immunohistochemically stained for cyclin E and evaluated regarding the presence of nuclear staining. The overall growth characteristics of each tumour were assessed using whole tissue sections.

Results: Tumours displaying a pushing margin phenotype were strongly associated with high cyclin E levels, lymph node negative disease, a high histological grade and oestrogen receptor negativity, and exhibited a better prognosis compared to tumours with an infiltrative growth pattern. In the total cohort of non-treated patients (n = 187), cyclin E was not associated with recurrence free survival (RFS). However, when analysing the subgroup of tumours lacking a pushing growth pattern (n = 141), cyclin E was significantly associated with RFS, independent of histological grade and node status. There was no significant difference in tamoxifen response with regard to different cyclin E levels.

Conclusion: The prognostic value of cyclin E in premenopausal breast cancer is limited to patients with breast carcinomas exhibiting an exclusively infiltrative growth pattern. This limitation could be explained by the presence of a small but distinct subgroup of cyclin E-high breast cancers with a pushing margin phenotype and a more favourable outcome.

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  • Funding: This study was supported by grants from the Swedish Research Council, the Swedish Cancer Society, Gunnar, Arvid and Elisabeth Nilsson Cancer Foundation, Lund University Research Funds, Per-Eric and Ulla Schybergs Foundation, Malmö University Hospital Research and Cancer Funds and Swegene/Wallenberg Consortium North.

  • Competing interests: None declared.