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

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Abstract

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.

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Acknowledgements

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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Authors and Affiliations

  1. Department of Surgery, Leiden University Medical Centre, Leiden, The Netherlands

    Johanna G. H. van Nes, Esther M. de Kruijf, Cornelis J. H. van de Velde & Peter J. K. Kuppen

  2. Endocrine Cancer Group, Department of Pathology, Cancer Research Center, Western General Hospital, Crewe Road South, Edinburgh, EH4 2XR, UK

    Dana Faratian, Claire Falconer, Charlene Kay & John M. S. Bartlett

  3. Department of Medical Statistics, Leiden University Medical Centre, Leiden, The Netherlands

    Hein Putter

  4. Department of Pathology, Leiden University Medical Centre, Leiden, The Netherlands

    Vincent T. H. B. M. Smit

  5. Department of Pathology, Amsterdam Medical Centre, Amsterdam, The Netherlands

    Marc J. van de Vijver

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  1. Johanna G. H. van Nes
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  2. Esther M. de Kruijf
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Correspondence to John M. S. Bartlett.

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van Nes, J.G.H., de Kruijf, E.M., Faratian, D. et al. COX2 expression in prognosis and in prediction to endocrine therapy in early breast cancer patients. Breast Cancer Res Treat 125, 671–685 (2011). https://doi.org/10.1007/s10549-010-0854-7

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