Chemoprevention of mammary carcinogenesis in female rats by rofecoxib

Epidemiological and experimental studies indicate that non-steroidal anti-inflammatory drugs play role in the prevention of human neoplasia including mammary gland cancer. In this study, tumour suppressive effects of a selective inhibitor of cyclooxygenase-2 (COX-2) rofecoxib in the prevention of N-methyl-N-nitrosourea (NMU)-induced mammary carcinogenesis in female Sprague–Dawley rats were evaluated. Rofecoxib was dietary administered in two concentrations—0.01 mg/1 g (ROFE 0.001%), or 0.05 mg/1 g (ROFE 0.005%). Rofecoxib decreased the incidence by 40% (ROFE 0.001%) and by 42.5% (ROFE 0.005%) (P=0.043) when compared to the control group. Similarly, tumour frequency and tumour volume decreased depending on an increasing rofecoxib dose by 18.5 or 40% (tumour frequency) and by 35 or 43% (tumour volume). Rofecoxib shifted the rate of fibroadenomas from 15% (control group) to 32% (ROFE 0.001%), or 38% (ROFE 0.005%), respectively. The present study points to pronounced dose-dependent tumour suppressive effects of rofecoxib in mammary carcinogenesis.