Soy Protein and Breast Cancer Risk Reduction

Soy consumption has been associated with reduced risk for developing breast cancer. Ovarian hormones and breast density are considered breast cancer risk markers. We propose to test the hypothesis that consumption of soy protein reduces ovarian steroid hormones and results in a corresponding reduction in breast density comparing to casein protein.

The aims will be tested by conducting a randomized, double-blind study, with two arms and 100 women in each arm. Premenopausal women will be recruited and randomly allocated to take one of two different dietary supplements daily for 2 years. The two test diets soy protein drink and caseinate protein drink. Multiple blood, urine, and breast fluid samples will be obtained before and during the dietary intervention period and analyzed for ovarian hormones. At baseline and after the intervention period, breast density, and bone density will be assessed by radiological techniques at baseline and 1 yr and 2 yr after protein drink supplementation. The efficacy of the dietary intervention will be determined by comparing mean changes of ovarian steroids, and density of the breast and bone tissues over the 2 year dietary intervention period in the two diet groups with adjustment for baseline values and individual patient characteristics of interest. We predict that 2 years of soya dietary supplements will reduce breast density, which will be explained by individual hormonal changes.

Research pharmacist dispensed blinded assigned sachets according to a pre-generated randomization list. Pharmacists were blinded to all other aspects of the research protocols. Subjects, investigators, research staff, and statisticians were all blinded to treatment assignment.

Subjects will consume two soy milk drinks from the content of 2 sachets (40 g isoflavone-free soy protein and 600 mg calcium) in place of a small meal, five days per week. Each sachet will contain 20 g soy protein and 300 mg calcium. Content of sachets will be mixed with ~1.6 liter of water for ingestion.

Subjects will consume two cow's milk drinks from the content of 2 sachets (40 g cow's milk protein, casein, and 600 mg calcium) in place of a small meal, five days per week. Each sachet will contain 20 g cow's milk protein and 300 mg calcium. Content of sachets will be mixed with ~1.6 liter of water for ingestion. Casein is free of ovarian hormones.

Each drink contained soy protein, fat, and carbohydrates calcium and phosphorous to give a total energy of 177.8 kcal. Subjects took two drinks per day.

Each drink contained casein, fat, carbohydrates, calcium and phosphorous to give a total energy of 178.6 kcal. Subjects took two drinks per day.

breast images to be measured by digital mammography and breast magnetic resonance imaging protocol, breast density is percent of fibroglandular tissue (radiologically dense) in whole breast tissue

Bone mineral content (gm) or bone mineral density (gm/cm2) to be measured by dual energy x-ray absorptiometry (DEXA) once at baseline, and then yearly after supplementation for up to 2 years.

Serum will be measured for estrogen (pg/ml), 4 times at baseline, and thereafter at 3-monthly interval for up to 2 years of protein drink supplementation

4 measurements at baseline and once every three months after protein drink supplements for up to 2 years.

Serum will be measured for progesterone (ng/ml), 4 times at baseline, and thereafter at 3-monthly interval for up to 2 years of protein drink supplementation

4 measurements at baseline and once every three months after protein drink supplements for up to 2 years.

Serum will be measured for for blood chemistries , 4 times at baseline, and thereafter at 3-monthly interval for up to 2 years of protein drink supplementation

4 measurements at baseline and once every three months after protein drink supplements for up to 2 years.

Only females with regular monthly menstrual cycles, not expecting to become pregnancy, not breast feeding, and not on contraceptives

Inclusion Criteria: healthy premenopausal women 30 to 40 years old normal mammograms regular menstrual cycles Exclusion Criteria: abnormal mammograms first degree relatives with breast cancer pregnant or lactating peri- or post-menopause breast augmentation, reduction, and lifting on oral contraceptive medications or exogenous hormones medically prescribed diets allergic reaction to soy or cow's milk

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