Pre-surgical study of the biological effects of the selective cyclo-oxygenase-2 inhibitor celecoxib in patients with primary breast cancer.
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.
Martin
Lesley-Ann
LA
Breakthrough Breast Cancer Research Centre, Institute of Cancer Research, Fulham Rd, London, SW3 6JB, UK. Lesley-Ann.Martin@icr.ac.uk
Davies
Giles L S
GL
Weigel
Marion T
MT
Betambeau
Nadine
N
Hills
Margaret J
MJ
Salter
Janine
J
Walsh
Geraldine
G
A'Hern
Roger
R
Dowsett
Mitch
M
D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D017209:Apoptosis / Q000187:drug effects; D001706:Biopsy; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology / Q000601:surgery; D000068579:Celecoxib; D049109:Cell Proliferation / Q000187:drug effects; D017024:Chemotherapy, Adjuvant; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D052246:Cyclooxygenase 2 Inhibitors / Q000008:administration & dosage*; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D019394:Ki-67 Antigen / Q000378:metabolism; D008131:London; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D009367:Neoplasm Staging; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D017698:Postmenopause; D011720:Pyrazoles / Q000008:administration & dosage*; D011960:Receptors, Estrogen / Q000378:metabolism; D011980:Receptors, Progesterone / Q000378:metabolism; D013449:Sulfonamides / Q000008:administration & dosage*; D013997:Time Factors; D016896:Treatment Outcome
D000970:Antineoplastic Agents; D052246:Cyclooxygenase 2 Inhibitors; D019394:Ki-67 Antigen; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D011720:Pyrazoles; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D013449:Sulfonamides; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D000068579:Celecoxib