Breast Cancer Research and Treatment

, Volume 125, Issue 3, pp 671–685 | Cite as

COX2 expression in prognosis and in prediction to endocrine therapy in early breast cancer patients

  • Johanna G. H. van Nes
  • Esther M. de Kruijf
  • Dana Faratian
  • Cornelis J. H. van de Velde
  • Hein Putter
  • Claire Falconer
  • Vincent T. H. B. M. Smit
  • Charlene Kay
  • Marc J. van de Vijver
  • Peter J. K. Kuppen
  • John M. S. Bartlett
Preclinical Study


In breast cancer, the prognostic impact of COX2 expression varies widely between studies. We examined the prognostic value of COX2 expression in a large cohort of breast cancer patients treated with primary surgery between 1985 and 1994 and explained the variable results of COX2 expression found in the literature. A tissue microarray was constructed of available tumour material, and ER, PgR, HER2, Ki67 and COX2 were examined by immunohistochemistry. Median follow-up was 19 years. Fifty-five percent (n = 369/677) of patients received no systemic treatment. COX2 was scored using a weighted histoscore. Analysis of COX2 expression in two groups based on the median (148; below vs. above) showed an increased hazard ratio (HR) of 1.35 (95% CI 1.05–1.75, P = 0.021) for disease-free survival (DFS) and of 1.39 (95% CI 1.03–1.82, P = 0.016) for overall survival (OS). However, COX2 did not remain independent in multivariate analysis. In patients with hormone receptor positive tumours, COX2 expression had a negative influence on outcome (low vs. high: DFS: HR 1.37, 95% CI 1.07–1.76, P = 0.013). This effect disappeared when endocrine therapy was administered (low vs. high: DFS: HR 0.93, 95% CI 0.51–1.70, P = 0.811) while it remained statistically significant when endocrine therapy was omitted (low vs. high: DFS: HR 1.48, 95% CI 1.12–1.94, P = 0.005). Our results show that COX2 plays a role in hormonal pathways. Our results can explain the results found in previously published studies.


Early breast cancer COX2 Prognostic and predictive factors Endocrine therapy 



We thank Fiona Campbell, Alison Munro, Johanna Pedraza, InHwa Um and other colleagues of the Endocrine Cancer Group for their help in the laboratory. We thank Jan Molenaar for help with the database and Klaas van der Ham for pictures of immunohistochemistry-stained slides. This research has been supported by grants of the Dutch Surgical Foundation ‘Stichting Prof. Michaël-van Vloten Fonds’, by the Foundation ‘De Drie Lichten’ in the Netherlands and by an unrestricted educational research grant of Pfizer UK.


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Copyright information

© Springer Science+Business Media, LLC. 2010

Authors and Affiliations

  • Johanna G. H. van Nes
    • 1
  • Esther M. de Kruijf
    • 1
  • Dana Faratian
    • 2
  • Cornelis J. H. van de Velde
    • 1
  • Hein Putter
    • 3
  • Claire Falconer
    • 2
  • Vincent T. H. B. M. Smit
    • 4
  • Charlene Kay
    • 2
  • Marc J. van de Vijver
    • 5
  • Peter J. K. Kuppen
    • 1
  • John M. S. Bartlett
    • 2
  1. 1.Department of SurgeryLeiden University Medical CentreLeidenThe Netherlands
  2. 2.Endocrine Cancer Group, Department of PathologyCancer Research Center, Western General HospitalEdinburghUK
  3. 3.Department of Medical StatisticsLeiden University Medical CentreLeidenThe Netherlands
  4. 4.Department of PathologyLeiden University Medical CentreLeidenThe Netherlands
  5. 5.Department of PathologyAmsterdam Medical CentreAmsterdamThe Netherlands

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