Breast Cancer Research and Treatment

, Volume 113, Issue 1, pp 75–82 | Cite as

Cyclin D1 expression is associated with poor prognostic features in estrogen receptor positive breast cancer

  • Kirsimari Aaltonen
  • Rose-Marie Amini
  • Göran Landberg
  • Hannaleena Eerola
  • Kristiina Aittomäki
  • Päivi Heikkilä
  • Heli Nevanlinna
  • Carl Blomqvist
Preclinical Study


Cyclins D1 and E play an important role in breast carcinogenesis. High cyclin E expression is common in hormone receptor negative and high grade aggressive breast cancer, whereas cyclin D1 in hormone receptor positive and low grade breast cancer. Experimental data has suggested that cyclin D1 and E mediate cell proliferation by different mechanisms in estrogen receptor (ER) positive and negative breast cancer. To test this hypotheses in large breast cancer material and to clarify the histopathological correlations of cyclin E and D1, especially the association with proliferation, we analyzed cyclin E and D1 immunohistochemical expression on breast tumour microarrays consisting of 1348 invasive breast cancers. High cyclin D1 expression was associated with high grade (P < 0.0005), high cyclin A (P < 0.0005) and Ki67 (P < 0.0005) expression among ER positive but with low grade (P = 0.05) and low Ki67 (P = 0.01) expression among ER negative breast cancers. Cyclin E and D1 expression correlated positively in ER positive (P < 0.0005) but had a negative correlation in ER negative tumours (P = 0.004). Cyclin E associated with high grade among all tumours (P < 0.0005). In conclusion, the findings of this study show that cyclin D1 has separate roles, and proliferation is driven by different mechanisms in ER positive and negative breast cancers.


Cyclin D1 Cyclin E Breast cancer Estrogen receptor Proliferation 



We wish to thank all the patients participating our study. Nina Puolakka is acknowledged for her work with the patient data, Maj-Lis Book for technical assistance, and Finnish Cancer Registry for the cancer data. The study was supported by grants from the Finnish Medical Foundation (Finska Läkaresällskapet), the Finnish Cancer Society, the Helsinki University Hospital Research Fund, the Sigrid Juselius Fund, and the Academy of Finland (110663).


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Copyright information

© Springer Science+Business Media, LLC. 2008

Authors and Affiliations

  • Kirsimari Aaltonen
    • 1
    • 2
  • Rose-Marie Amini
    • 3
  • Göran Landberg
    • 4
  • Hannaleena Eerola
    • 1
    • 2
  • Kristiina Aittomäki
    • 5
  • Päivi Heikkilä
    • 6
  • Heli Nevanlinna
    • 2
  • Carl Blomqvist
    • 1
    • 7
  1. 1.Department of OncologyHelsinki University Central HospitalHelsinkiFinland
  2. 2.Department of Obstetrics and GynaecologyHelsinki University Central HospitalHelsinkiFinland
  3. 3.Department of Genetics and PathologyUppsala University HospitalUppsalaSweden
  4. 4.Division of Pathology, Institution of Laboratory MedicineMalmö University HospitalMalmoSweden
  5. 5.Department of Clinical GeneticsHelsinki University Central HospitalHelsinkiFinland
  6. 6.Department of PathologyHelsinki University Central HospitalHelsinkiFinland
  7. 7.Department of Oncology, Radiology and Clinical ImmunologyUppsala University HospitalUppsalaSweden

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