Breast Cancer
Conditions
Keywords
soy diet, breast cancer, ovarian hormones, breast density, prevention
Brief summary
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.
Detailed description
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.
Interventions
DIETARY_SUPPLEMENTsoy milk
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.
DIETARY_SUPPLEMENTcow's milk
Each drink contained casein, fat, carbohydrates, calcium and phosphorous to give a total energy of 178.6 kcal. Subjects took two drinks per day.
Sponsors
U.S. Army Medical Research and Development Command
National Center for Research Resources (NCRR)
The University of Texas Medical Branch, Galveston
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
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.
Intervention model description
Randomized, double-blind, placebo controlled, 2 parallel groups
Eligibility
Sex/Gender
FEMALE
Age
30 Years to 40 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mammographic Density (Baseline) | Baseline | Breast images were acquired by digital mammography. Fibroglandular tissue were segmented from fatty breast tissue. The total breast area is the sum of the fibroglandular tissue area and fatty breast tissue area. Mammographic density (breast density) is the percentage of fibroglandular tissue in the total breast. |
| Breast Tissue Composition Measured by MRI | Baseline | Breast images acquired by breast magnetic resonance imaging (MRI). The amount of fatty breast tissue,(cc), glandular breast tissue(cc ), total breast (cc), and percentage of glandular tissue in total breast (%) were estimated. |
| Percentage of Grandular Tissue in Total Breast Measured by MRI | Baseline | Breast images acquired by breast magnetic resonance imaging (MRI). The amount of fatty breast tissue,(cc), glandular breast tissue(cc ), total breast (cc), and percentage of glandular tissue in total breast (%) were estimated. |
| Mammographic Density (2 Years) | 2 years | Breast images were acquired by digital mammography. Fibroglandular tissue were segmented from fatty breast tissue. The total breast area is the sum of the fibroglandular tissue area and fatty breast tissue area. Mammographic density (breast density) is the percentage of fibroglandular tissue in the total breast. |
| Mammographic Density (1 Year) | 1 Year | Breast images were acquired by digital mammography. Fibroglandular tissue were segmented from fatty breast tissue. The total breast area is the sum of the fibroglandular tissue area and fatty breast tissue area. Mammographic density (breast density) is the percentage of fibroglandular tissue in the total breast. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Progesterone (ng/ml) | 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 |
| Blood Will be Measured for Standard Clinical Chemistries | 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 |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Soy Milk 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.
soy milk: 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. | 161 |
| Cow's Milk 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.
cow's milk: Each drink contained casein, fat, carbohydrates, calcium and phosphorous to give a total energy of 178.6 kcal. Subjects took two drinks per day. | 160 |
| Total | 321 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| One Year After Diet | Did not complete 1 year of diet | 42 | 38 |
| Two Years After Diet | Did not complete the 2nd year of diet | 16 | 13 |
Baseline characteristics
| Characteristic | Soy Milk | Cow's Milk | Total |
|---|---|---|---|
| Age, Customized Ages from 29 to 41 | 161 years | 0 years | 161 years |
| Age, Customized Agesfrom 30 to 41 | 0 years | 160 years | 160 years |
| Race/Ethnicity, Customized American Indian/Alaskan | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Asian | 2 Participants | 3 Participants | 5 Participants |
| Race/Ethnicity, Customized Black/African American | 21 Participants | 18 Participants | 39 Participants |
| Race/Ethnicity, Customized Caucasian | 77 Participants | 66 Participants | 143 Participants |
| Race/Ethnicity, Customized Hispanic or Latino | 57 Participants | 71 Participants | 128 Participants |
| Race/Ethnicity, Customized Other (>2 races) | 3 Participants | 2 Participants | 5 Participants |
| Region of Enrollment United States | 161 participants | 160 participants | 321 participants |
| Sex: Female, Male Female | 161 Participants | 160 Participants | 321 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 161 | 0 / 160 |
| other Total, other adverse events | 28 / 161 | 21 / 160 |
| serious Total, serious adverse events | 0 / 161 | 0 / 160 |
Outcome results
Primary
Breast Tissue Composition Measured by MRI
Breast images acquired by breast magnetic resonance imaging (MRI). The amount of fatty breast tissue,(cc), glandular breast tissue(cc ), total breast (cc), and percentage of glandular tissue in total breast (%) were estimated.
Time frame: 1 Year
Population: Participants completed year 1.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Soy Milk | Breast Tissue Composition Measured by MRI | Fatty Breast Tissue, cc | 587.4 cc | Standard Deviation 341.8 |
| Soy Milk | Breast Tissue Composition Measured by MRI | Glandular Breast Tissue, cc | 159.3 cc | Standard Deviation 89.72 |
| Soy Milk | Breast Tissue Composition Measured by MRI | Total Breast, cc | 746.7 cc | Standard Deviation 358.8 |
| Cow's Milk | Breast Tissue Composition Measured by MRI | Fatty Breast Tissue, cc | 626.1 cc | Standard Deviation 358.9 |
| Cow's Milk | Breast Tissue Composition Measured by MRI | Glandular Breast Tissue, cc | 156.7 cc | Standard Deviation 83.06 |
| Cow's Milk | Breast Tissue Composition Measured by MRI | Total Breast, cc | 782.8 cc | Standard Deviation 387.5 |
Primary
Breast Tissue Composition Measured by MRI
Breast images acquired by breast magnetic resonance imaging (MRI). The amount of fatty breast tissue,(cc), glandular breast tissue(cc ), total breast (cc), and percentage of glandular tissue in total breast (%) were estimated.
Time frame: 2 years
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Soy Milk | Breast Tissue Composition Measured by MRI | Fatty Breast Tissue, cc | 629.9 cc | Standard Deviation 406.5 |
| Soy Milk | Breast Tissue Composition Measured by MRI | Glandular Breast Tissue, cc | 173.8 cc | Standard Deviation 104.5 |
| Soy Milk | Breast Tissue Composition Measured by MRI | Total Breast, cc | 803.7 cc | Standard Deviation 420.8 |
| Cow's Milk | Breast Tissue Composition Measured by MRI | Fatty Breast Tissue, cc | 615.5 cc | Standard Deviation 395.9 |
| Cow's Milk | Breast Tissue Composition Measured by MRI | Glandular Breast Tissue, cc | 152.7 cc | Standard Deviation 87.44 |
| Cow's Milk | Breast Tissue Composition Measured by MRI | Total Breast, cc | 768.2 cc | Standard Deviation 426.4 |
Primary
Breast Tissue Composition Measured by MRI
Breast images acquired by breast magnetic resonance imaging (MRI). The amount of fatty breast tissue,(cc), glandular breast tissue(cc ), total breast (cc), and percentage of glandular tissue in total breast (%) were estimated.
Time frame: Baseline
Population: 4 participants images in the cow's milk and 14 images in soy milk were either missing or corrupt.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Soy Milk | Breast Tissue Composition Measured by MRI | Fatty Breast Tissue, cc | 589.9 cc | Standard Deviation 333.5 |
| Soy Milk | Breast Tissue Composition Measured by MRI | Glandular Breast Tissue, cc | 153.4 cc | Standard Deviation 84.48 |
| Soy Milk | Breast Tissue Composition Measured by MRI | Total Breast, cc | 743.3 cc | Standard Deviation 350.9 |
| Cow's Milk | Breast Tissue Composition Measured by MRI | Fatty Breast Tissue, cc | 628.1 cc | Standard Deviation 373.4 |
| Cow's Milk | Breast Tissue Composition Measured by MRI | Glandular Breast Tissue, cc | 156.7 cc | Standard Deviation 88.75 |
| Cow's Milk | Breast Tissue Composition Measured by MRI | Total Breast, cc | 784.9 cc | Standard Deviation 400.8 |
Primary
Mammographic Density (1 Year)
Breast images were acquired by digital mammography. Fibroglandular tissue were segmented from fatty breast tissue. The total breast area is the sum of the fibroglandular tissue area and fatty breast tissue area. Mammographic density (breast density) is the percentage of fibroglandular tissue in the total breast.
Time frame: 1 Year
Population: Participants completed one year of diet.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Soy Milk | Mammographic Density (1 Year) | 29.37 percentage of glandular tissue in breast | Standard Deviation 12.78 |
| Cow's Milk | Mammographic Density (1 Year) | 28.01 percentage of glandular tissue in breast | Standard Deviation 11.56 |
Primary
Mammographic Density (2 Years)
Breast images were acquired by digital mammography. Fibroglandular tissue were segmented from fatty breast tissue. The total breast area is the sum of the fibroglandular tissue area and fatty breast tissue area. Mammographic density (breast density) is the percentage of fibroglandular tissue in the total breast.
Time frame: 2 years
Population: Participants completed 2 years of study. 1 image missing from the cow's milk group due to it was corrupt.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Soy Milk | Mammographic Density (2 Years) | 30.75 percentage of glandular tissue in breast | Standard Deviation 13.26 |
| Cow's Milk | Mammographic Density (2 Years) | 29.06 percentage of glandular tissue in breast | Standard Deviation 11.8 |
Primary
Mammographic Density (Baseline)
Breast images were acquired by digital mammography. Fibroglandular tissue were segmented from fatty breast tissue. The total breast area is the sum of the fibroglandular tissue area and fatty breast tissue area. Mammographic density (breast density) is the percentage of fibroglandular tissue in the total breast.
Time frame: Baseline
Population: 4 participants images in the cow's milk and 3 images in soy milk were either missing or corrupt.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Soy Milk | Mammographic Density (Baseline) | 29.21 percentage of glandular tissue in breast | Standard Deviation 11.44 |
| Cow's Milk | Mammographic Density (Baseline) | 28.24 percentage of glandular tissue in breast | Standard Deviation 11.77 |
Primary
Percentage of Grandular Tissue in Total Breast Measured by MRI
Breast images acquired by breast magnetic resonance imaging (MRI). The amount of fatty breast tissue,(cc), glandular breast tissue(cc ), total breast (cc), and percentage of glandular tissue in total breast (%) were estimated.
Time frame: Baseline
Population: 4 participants images in the cow's milk and 14 images in soy milk were either missing or corrupt.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Soy Milk | Percentage of Grandular Tissue in Total Breast Measured by MRI | 24.27 % of glandular tissue in total breast | Standard Deviation 13.64 |
| Cow's Milk | Percentage of Grandular Tissue in Total Breast Measured by MRI | 24.09 % of glandular tissue in total breast | Standard Deviation 15.83 |
Primary
Percentage of Grandular Tissue in Total Breast Measured by MRI
Breast images acquired by breast magnetic resonance imaging (MRI). The amount of fatty breast tissue,(cc), glandular breast tissue(cc ), total breast (cc), and percentage of glandular tissue in total breast (%) were estimated.
Time frame: 1 Year
Population: Participants completed year 1.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Soy Milk | Percentage of Grandular Tissue in Total Breast Measured by MRI | 25.017 % of glandular tissue in total breast | Standard Deviation 14.48 |
| Cow's Milk | Percentage of Grandular Tissue in Total Breast Measured by MRI | 24.20 % of glandular tissue in total breast | Standard Deviation 15.82 |
Primary
Percentage of Grandular Tissue in Total Breast Measured by MRI
Breast images acquired by breast magnetic resonance imaging (MRI). The amount of fatty breast tissue,(cc), glandular breast tissue(cc ), total breast (cc), and percentage of glandular tissue in total breast (%) were estimated.
Time frame: 2 years
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Soy Milk | Percentage of Grandular Tissue in Total Breast Measured by MRI | 26.39 % of glandular tissue in total breast | Standard Deviation 15.52 |
| Cow's Milk | Percentage of Grandular Tissue in Total Breast Measured by MRI | 24.25 % of glandular tissue in total breast | Standard Deviation 15.89 |
Other Pre-specified
Blood Will be Measured for Standard Clinical Chemistries
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
Time frame: 4 measurements at baseline and once every three months after protein drink supplements for up to 2 years.
Other Pre-specified
Progesterone (ng/ml)
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
Time frame: 4 measurements at baseline and once every three months after protein drink supplements for up to 2 years.