MEDICAL HYPOTHESIS - XENOESTROGENS AS PREVENTABLE CAUSES OF BREAST-CANCER

Changes in documented risk factors for breast cancer and rates of scre ening cannot completely explain recent increases in incidence or morta lity. Established risk factors for breast cancer, including genetics a ccount for at best 30% of cases. Most of these risk factors can be lin ked to total lifetime exposure to bioavailable estrogens. Experimental evidence reveals that compounds such as some chlorinated organics, po lycyclic aromatic hydrocarbons (PAHs), triazine herbicides, and pharma ceuticals affect estrogen production and metabolism and thus function as xenoestrogens. Many of these xenoestrogenic compounds also experime ntally induce mammary carcinogenesis. Recent epidemiologic studies haw found that breast fat and serum lipids of women with breast cancer co ntain significantly elevated levels of some chlorinated organics compa red with noncancer controls. As the proportion of inherited breast can cer in the population is small, most breast cancers are due to acquire d mutations. Thus, the induction of breast cancer in the majority of c ases stems from interactions between host factors, including genetics and environmental carcinogens. We hypothesize that substances such as xenoestrogens increase the risk of breast cancer by mechanisms which i nclude interaction with breast-cancer susceptibility genes. A series o f major epidemiologic studies need to be developed to evaluate this hy pothesis, including studies of estrogen metabolism, like role of speci fic xenoestrogenic substances in breast cancer, and relevant genetic-e nvironmental interactions. In addition, experimental studies are neede d to evaluate biologic markers of suspect xenoestrogenic and biologic markers of host susceptibility and identify pathways of estrogenicity that affect the development of breast cancer. If xenoestrogens do play a role in breast cancer, reductions in exposure will provide an oppor tunity for primary prevention of this growing disease. Tests for estro genicity could become critical screening tools with which to the poten tial health consequences of new and existing chemicals.