The estrogen dependence of many human breast tumors, the association of breast cancer risks with early menarche and late menopause, and the dramatic effect of oophorectomy on breast cancer risk all point to a role of estrogens in the etiology of breast cancer. In experimental and epidemological studies breast cancer patients and women at high risk for breast cancer have elevated urinary and serum estrogen levels. Diet may also be associated with the incidence of breast cancer. Fat intakes show positive correlations with breast cancer incidence in cross-country surveys. Finally, studies from our laboratory have demonstrated that diet can alter the excretion pattern of estrogens and in turn can affect plasma estrogen levels. The proposed study investigates the effect of diet on estrogen status and metabolism. Thirty premenopausal women will be placed on a strictly controlled Western diet with high fat (40% of calories) and low fiber content (10-12 gm). Subjects wil then be shifted to one of 3 experimental diets; a low fat-high fiber, high fat-high fiber, or a high fat-high fiber isocaloric diet. All meals will be prepared and consumed at a metabolic table. Plasma estrogens, androgens, sex hormone binding globulin, prolactin, progesterone and 2-hydroxyestrone will be measured. These determinations will be done during both baseline and experimental periods and over the midfollicular, ovulatory and luteal phases of the menstrual cycle. Fecal specimens will be tested for Beta-glucuronidase activity and androgen and estrogen converting ability, to ascertain if diet mediates its effect via alteration of the intestinal flora. Five women will be given an antibiotic on the high fat-low fiber diet to determine whether suppression of the intestinal flora affects plasma estrogens via the changes in the enterohepatic circulation. 3H-estradiol will be given to 15 women before and after the dietary alteration in order to measure clearance and production rates of estradiol and its conversion to catechol estrogens. Ten postmenopausal women will be fed the diet having greatest effects on estradiol metabolism and hormone measurements will be taken. An understanding of the effects of fat and fiber on estrogen levels is an important step in the exploration of ways to reduce the frequency of breast cancer in high risk population.
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