CHEMOPREVENTION OF BREAST-CANCER BY TAMOXIFEN - RISKS AND OPPORTUNITIES

The antioestrogen tamoxifen is of proven efficacy in inhibiting the gr owth of oestrogen receptor positive breast cancers in women. In rats, long-term dosing leads to the development of hepatocellular tumours. T amoxifen in this species is a genotoxic carcinogen. Metabolic activati on by cytochrome P450-dependent enzymes leads to DNA damage detectable by P-32-postlabelling. Factors important in the development of hepato cellular lesions were the nature and quantity of metabolism and promot ion/progression of the DNA lesion by agents such as phenobarbital and cell proliferation. No evidence was found for tamoxifen-induced DNA da mage in the livers of 7 women taking this drug therapeutically.