RETINOIDS AND TAMOXIFEN IN BREAST-CANCER CHEMOPREVENTION

Chemoprevention is a new branch of oncology which aims to use chemical agents to reduce the incidence of malignant diseases in humans. On the basis of a growing mass of experimental data, it is now felt that the importance of early, precursor lesions of clinically symptomatic cancer should be recognized. Just as in cardiovascular disease, there is now major emphasis on the natural history of tumors and some authors believe that the actual disease process is carcinogenesis, rather than cancer. Indeed, as the chemoprevention of cardiovascular illness with pharmacological agents that either lower blood cholesterol or prevent platelet aggregation is widespread, the effectiveness of different chemical compounds in preventing cancer or, at least in delaying its onset, is presently under investigation. For breast cancer, various agents have been suggested as having chemopreventive effects: vitamins C and E, difluoromethylornithine, selenium, retinoids and antiestrogens. Among retinoids, 4-(N-hydroxyphenyl)retinamide, fenretinide, is at present the most promising molecule, due to its ability to concentrate in the mammary gland. Attention has recently been focussed on tamoxifen because of its effectiveness in reducing the incidence of contralateral tumors in breast cancer patients. Finally, the recent discovery of the steroid receptor superfamily is expected to stimulate further research into combination chemoprevention (the use of multiple agents to achieve synergistic effects while diminishing toxicity). As retinoids and tamoxifen both increase the synthesis or activity of transforming growth factor-beta, a cytokine which is a potent inhibitor of epithelial cell proliferation, tamoxifen and fenretinide are now proposed as the first model of combination chemoprevention in breast cancer.