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

• Published in: Breast cancer research and treatment 2010-10, Vol.123 (3), p.829-836
• Main Authors: Martin, Lesley-Ann, Davies, Giles L. S, Weigel, Marion T, Betambeau, Nadine, Hills, Margaret J, Salter, Janine, Walsh, Geraldine, A'Hern, Roger, Dowsett, Mitch
• Format: Article
• Language: English
• Subjects: Aged; Aged, 80 and over; Analysis; Antineoplastic Agents - administration & dosage; Apoptosis - drug effects; Biological and medical sciences; Biopsy; Breast cancer; Breast Neoplasms - drug therapy; Breast Neoplasms - enzymology; Breast Neoplasms - pathology; Breast Neoplasms - surgery; Cancer patients; Cancer research; Cancer therapies; Celecoxib; Cell Proliferation - drug effects; Chemotherapy, Adjuvant; Clinical Trial; Clinical trials; COX-2; COX-2 inhibitors; Cyclooxygenase 2 - metabolism; Cyclooxygenase 2 Inhibitors - administration & dosage; Drug Administration Schedule; Effects; Estrogen; Estrogen receptor; Female; Gynecology. Andrology. Obstetrics; Humans; Ki-67 Antigen - metabolism; Ki67; London; Mammary gland diseases; Medical sciences; Medicine; Medicine & Public Health; Middle Aged; Neoadjuvant Therapy; Neoplasm Staging; Nonsteroidal anti-inflammatory drugs; Oncology; Platelet Endothelial Cell Adhesion Molecule-1 - metabolism; Postmenopausal women; Postmenopause; Pre-surgical study; Progesterone; Pyrazoles - administration & dosage; Receptors, Estrogen - metabolism; Receptors, Progesterone - metabolism; Sulfonamides - administration & dosage; Time Factors; Treatment Outcome; Tumors
• ISSN: 0167-6806; 1573-7217
• DOI: 10.1007/s10549-010-1100-z

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.