4-Hydroxyandrostenedione in the prophylaxis of N-methyl-N-nitrosourea induced mammary tumourigenesis

Abstract

We have examined the role of the aromatase inhibitor 4-hydroxyandrostenedione (4-OHA) in the prevention of mammary tumourigenesis in experiments involving 170 rats. We first demonstrated a prophylactic effect of 4-OHA (50 mg/week) in reducing tumour incidence over a 30 week period compared to controls (P = 0.04). We repeated the experiment to determine optimum dose and duration of therapy. Although 4-OHA again prevented tumour development (P less than 0.0005), there was no difference between the standard (50 mg/week) dose and the higher dose (100 mg/week). Rats were randomised at 30 weeks to either stop or to continue prophylactic therapy; marginal benefit in tumour free survival in continuing therapy was observed (P = 0.03). We conclude that 4-OHA is an effective agent in preventing carcinogen-induced mammary tumours in rats and further studies of the role of oestrogen synthesis inhibitors in the prevention of human mammary tumours may be indicated.