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

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 (2, 1)

1 Breakthrough Breast Cancer Research Centre
2 Department of Academic Biochemistry
3 Department of Medicine Breast Unit

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% ( = 0.056). The change in the no-treatment group was −8.1% ( = 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.

Mots clés: Estrogen receptor; COX-2; Celecoxib; Pre-surgical study; Ki67

Lesley-Ann Martin, Giles L. S. Davies, Marion T. Weigel, Nadine Betambeau, Margaret J. Hills, et al.. Pre-surgical study of the biological effects of the selective cyclo-oxygenase-2 inhibitor celecoxib in patients with primary breast cancer. Breast Cancer Research and Treatment, 2010, 123 (3), pp.829-836. ⟨10.1007/s10549-010-1100-z⟩. ⟨hal-00564774⟩