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Cyclooxygenase (Cox-2) exerts a proangiogenic and anti-apoptotic effect in human cancers via its prostaglandin metabolites.We have demonstrated previously that breast cancer is accompanied by an unfavourable alteration in the proangiogenic cytokine,VEGF, which is increased in the peri-operative period. Experimental use of selective Cox-2 inhibitors in an orthothopic murine model of breast cancer reduces VEGF and decreases primary tumour and metastatic disease We hypothesise that peri-operative Cox-2 inhibition reduces serum and plasma VEGF in patients undergoing breast cancer surgery. Prospective pilot study of female breast cancer patients. Patients were randomised to receive the selective Cox-2 inhibitor, celecoxib (200 mg po bd) daily from day of diagnosis until two weeks postoperatively (n = 20/group) or no treatment (n = 20/group). Serum and plasma samples were taken on day of diagnosis (5–7 days pre-op), day of surgery, days 1, 3 and 14 postoperatively and assayed for VEGF. The control patients results confirm the VEGF elevation in breast cancer patients and the fact that surgery is associated with persistence in the first 14 days. Cox-2 inhibition in the peri-operative period is associated with a significant reduction in plasma and serum VEGF levels. These data suggest that peri-operative treatment with Cox-2 inhibitors may favourably modulate the proangiogenic effect of excisional surgery in breast cancer patients. TABLE—ABSTRACT 13 . VEGF (PG/ML) Control P-VEGF Cox-2 P-VEGF Control S-VEGF ∗ Cox-2 S-VEGF # Pretreatment 74.5 ± 11.9 103.7 ± 9.8 328.6 ± 25 336.1 ± 72.5 Preoperative 75.7 ± 11.2 88.4 ± 6.2 340.5 ± 22.7 241.8 ± 51.4 Day 1 postop 114.4 ± 7.1 101.6 ± 7.2 440.8 ± 28.8 294.1 ± 53.0 Day 3 postop 142.3 ± 14.1 106.9 ± 9.2 477.9 ± 44.3 326.8 ± 43.5 Day 14 postop 129.6 ± 21.2 106.7 ± 7.6 395.3 ± 88.6 396.5 ± 87.2 = P Data expressed as mean ± SEM. ANOVA post-hoc statistical analysis. ∗ Serum and # Plasma VEGF.