Future possibilities in the prevention of breast cancer: Role of genetic variation in breast cancer prevention

The traditional view of public health prevention strategies considers three broad categories. Primary prevention involves activities that are aimed at reducing and removing agents that increase risk. Secondary prevention includes early detection activities that are designed to reduce mortality. Finally, tertiary prevention aims to minimize or reduce long-term disability and suffering. Cancer prevention usually implies activities involved in primary or secondary prevention. For many cancer sites, we have made significant contributions in prevention. For example, the Pap smear has had a great impact on cervical cancer, and refrigeration and other safe food preservation practices have markedly reduced the incidence of stomach cancer. Largely because of the underlying hormonal etiology, however, primary prevention strategies for breast cancer have been limited.The biggest determinants of breast cancer risk are related to endogenous hormone levels and major reproductive events, and thus do not lend themselves to traditional prevention strategies. Table 1 lists the established breast cancer risk factors. Those with the greatest impact on risk are listed first, and unfortunately are the most difficult to modify by traditional public health measures. For example, surgical removal of the ovaries can hasten the onset of menopause, but is not considered a reasonable approach to reduce the risk of breast cancer. Age at menarche and the establishment of regular menstrual cycles may be delayed by vigorous physical activity and possibly diet, but rarely is breast cancer prevention a concern before menarche occurs.Limiting the use of alcohol, hormone replacement therapy (HRT), and oral contraceptives may reduce the risk of breast cancer, but the impact of these factors on breast cancer risk are modest. Furthermore, these agents have significant beneficial effects on the risks of other chronic diseases, and these risk-benefit ratios must be carefully weighed. Prolonged lactation may