INTERACTIONS BETWEEN HORMONES AND CHEMICALS IN BREAST-CANCER

Development of breast cancer in women is dependent on diverse factors, including genetic predisposition, exposure to both exogenous and endo genous chemicals, which can modulate initiation, promotion and progres sion of this disease, and the timing of exposure to these agents. Seve ral compounds-including 16 alpha-hydroxyestrone (16 alpha-OHE1), catec holestrogens, and aromatic amines-have been proposed as initiators of mammary carcinogenesis in humans; however, their role as genotoxins is unconfirmed. Lifetime exposure to estrogens has been established as a n important risk factor for breast cancer, and it has been suggested t hat xenoestrogens may directly add to the hormonal risk or indirectly increase risk by decreasing 2-hydroxyestrone (2-OHE1)/16 alpha-OHE1 me tabolite ratios. Results of recent studies suggest that chemical-induc ed modulation of 2-OHE1/16 alpha-OHE1 metabolite ratios is not predict ive of xenoestrogens or mammary carcinogens. Moreover, based on curren t known dietary intakes of natural and xenoestrogenic/antiestrogenic c hemicals, it is unlikely that xenoestrogens contribute significantly t o a woman's overall lifetime exposure to estrogens. More information i s required on the identities and serum levels of both natural and xeno endocrine active compounds, their concentrations in serum, and the mam mary gland and levels of these compounds at critical periods of exposu re.