An appraisal of strategies to reduce the incidence of breast cancer.

The current focus of breast cancer research is to develop a novel strategy to prevent the disease. In this review a potential model of breast cancer development is proposed based upon the results of laboratory models of the induction of mammary carcinogenesis. It is clear that susceptibility to initiation occurs in young female animals, and a preventive strategy is more effective the sooner it is started after initiation occurs. In humans we do not know the timing or the nature of the carcinogenic insult, but epidemiologic studies suggest that the process is long and initiation is most likely to occur in young adults. Hormones are the key to promotion of the carcinogenic process and it would appear that strategically the earlier an intervention is applied after initiation the better will be the general effect on the population. Hormonal contraception could prevent breast cancer if the appropriate formulation was chosen and used by all young women. This inhibitory strategy might protect women without the need to preselect based on risk factors. Breast cancer prevention would be a side effect of the contraceptive method. Alternatively, tamoxifen, an antiestrogen, is known to prevent mammary carcinogenesis in animals and prevent the appearance of second primary breast cancers in women. This well tested therapeutic agent is currently being evaluated in clinical trials of selected high-risk women aged 35 and above. Finally, retinoids have shown promise as agents in the laboratory to prevent cell replication and inhibit mammary tumorigenesis. A trial of retinoids to prevent second primary tumors in node negative breast cancer patients is currently underway in Italy. The review discusses the relative merits and concerns about these prevention strategies and proposes additional studies to be undertaken.