Breast Cancer Research and Treatment

, Volume 123, Issue 3, pp 829–836

Pre-surgical study of the biological effects of the selective cyclo-oxygenase-2 inhibitor celecoxib in patients with primary breast cancer

  • Lesley-Ann Martin
  • Giles L. S. Davies
  • Marion T. Weigel
  • Nadine Betambeau
  • Margaret J. Hills
  • Janine Salter
  • Geraldine Walsh
  • Roger A’Hern
  • Mitch Dowsett
Clinical trial

DOI: 10.1007/s10549-010-1100-z

Cite this article as:
Martin, LA., Davies, G.L.S., Weigel, M.T. et al. Breast Cancer Res Treat (2010) 123: 829. doi:10.1007/s10549-010-1100-z

Abstract

Cyclo-oxygenase 2 (COX-2) is implicated in the regulation of aromatase transcription in malignant breast tissue and has been considered as a potential target for tissue specific aromatase suppression. We initiated a randomised controlled pre-surgical study of celecoxib versus no treatment in women with primary breast cancer to determine the effects of COX-2 inhibition on markers of biological response. Postmenopausal women (50–80 years of age) with stage I or II, primary breast cancer, were randomised 2:1 to receive 400 mg/day celecoxib or no treatment for 14 days prior to surgery. A core biopsy was obtained pre- and post-treatment. Paired baseline and endpoint biopsies were analysed for Ki67, apoptosis, COX-2, CD31, estrogen receptor (ER) and progesterone receptor (PgR). Comparisons between the treatment groups were conducted using the Mann–Whitney test with a two-sided 5% significance. Of the 25 patients treated, 23 had evaluable data and 19 (83%) were ER positive. Overall the geometric mean change in Ki67, the primary end point, relative to baseline in the celecoxib arm was −16.6% (P = 0.056). The change in the no-treatment group was −8.1% (P = 0.24). There was no statistically significant difference in the change between the two groups. Celecoxib did not significantly affect apoptosis, COX-2, ER or PgR expression. There is only modest evidence for a biological effect of celecoxib in primary breast cancer. However, the trend towards a reduction in Ki67 in ER-positive breast cancer warrants further investigations in a larger cohort of patients.

Keywords

Estrogen receptor COX-2 Celecoxib Pre-surgical study Ki67 

Copyright information

© Springer Science+Business Media, LLC. 2010

Authors and Affiliations

  • Lesley-Ann Martin
    • 1
  • Giles L. S. Davies
    • 2
  • Marion T. Weigel
    • 1
  • Nadine Betambeau
    • 2
  • Margaret J. Hills
    • 2
  • Janine Salter
    • 2
  • Geraldine Walsh
    • 3
  • Roger A’Hern
    • 2
  • Mitch Dowsett
    • 1
    • 2
  1. 1.Breakthrough Breast Cancer Research CentreInstitute of Cancer ResearchLondonUK
  2. 2.Department of Academic BiochemistryRoyal Marsden HospitalLondonUK
  3. 3.Department of Medicine Breast UnitThe Royal Marsden HospitalLondonUK