Breast Cancer
Conditions
Keywords
soy, isoflavones, phytoestrogens, prevention, mammographic density, bone density
Brief summary
Soy consumption has been associated with reduced risk for developing breast cancer. Soy contains isoflavones which are weak estrogens. The roles of soy isoflavones in reducing breast cancer risk are currently unclear. Breast density has been considered as a breast cancer risk marker. We hypothesize that because isoflavones have estrogen-like activities, breast density and possibly bone density will be lower in women on soy-isoflavones.
Detailed description
This is 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 the two different dietary supplements in pills daily for 2 years. The two supplements are soy isoflavones (treatment) and placebo (carbohydrates). Both treatment and placebo pills will contain multi-vitamins and minerals. Multiple blood, urine, and breast fluid samples will be obtained before and during the dietary supplement periods and analyzed for biomarkers of breast cancer risk. At baseline and after the intervention period, breast density and bone density will be assessed by radiologic techniques. The efficacy of the dietary intervention will be determined by comparing mean changes of serum markers for breast cancer risk,dense breast tissue, and bone mineral density over the two year dietary intervention period in the two supplement groups with adjustment for baseline values and individual patient characteristics of interest. We predict that 2 years of soy isoflavone supplement will reduce breast density, which may be explained by individual changes in serum markers of breast cancer risk.
Interventions
DIETARY_SUPPLEMENTisoflavones
soy isoflavones: Each tablet contains 246 mg Novasoy, 676 mg calcium, 15 mg riboflavin, and other innert materials to a total weight of 1000 mg. Subject takes two isoflavone tablets plus 1 multi-vitamin per day for five days per week for upto 2 years.
DIETARY_SUPPLEMENTcarbohydrate
carbohydrate: 246 mg maltodextrin, 676 mg calcium, 15 mg riboflavin and other innert ingredients to a total weight of 1000 mg per tablet. subject takes two tablets plus one multivitamin per day for five days per week for upto 2 years.
Sponsors
National Cancer Institute (NCI)
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 study pills according to a pre-generated randomization list and were blinded to all other aspects of the study protocol. Subjects, research staff, investigators, and statistician all were blinded to treatment assignment.
Intervention model description
One group received soy isoflavones (60 mg daidzein, 60 mg gensitein and 16.6 mg glycitein, all as aglycone equivalent) Another group, carbohydrate filler
Eligibility
Sex/Gender
FEMALE
Age
30 Years to 42 Years
Healthy volunteers
Yes
Inclusion criteria
* healthy premenopausal women * 30 to 42 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 or lifting * on oral contraceptive medications or exogenous hormones * medically prescribed diets * allergic reaction to soy products
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Fibroglandular Tissue in Total Breast (FGBT%) | baseline, and after year 1 and 2 of supplementation | Effects of 1 and 2 years of treatment with isoflavones on percent of changes in FGBT%. |
| Breast Density by Mammography | baseline, and after year 1 and 2 of supplementation | Area of FGBT in mammogram. The timepoints were combined and summed. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Bone Mineral Density | one and two years after dietary supplement | Bone mineral density of hip, spine and whole body bone mineral density as measured by dual x-ray absorptiometry. The timepoints were combined and summed. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Soy Isoflavones Each tablet contains 246 mg Novasoy, 676 mg calcium, 15 mg riboflavin, and other inert materials to a total weight of 1000 mg. Subject takes two isoflavone tablets plus 1 multi-vitamin per day for five days per week for up to 2 years. | 99 |
| Placebo Carbohydrate: 246 mg maltodextrin, 676 mg calcium, 15 mg riboflavin and other inert ingredients to a total weight of 1000 mg per tablet. subject takes two tablets plus one multivitamin per day for five days per week for up to 2 years. | 98 |
| Total | 197 |
Baseline characteristics
| Characteristic | Soy Isoflavones | Placebo | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 99 Participants | 98 Participants | 197 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 51 Participants | 39 Participants | 90 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 48 Participants | 59 Participants | 107 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| FGBT% | 24.76 percentage of total breast STANDARD_DEVIATION 14.54 | 23.86 percentage of total breast STANDARD_DEVIATION 13.99 | 24.3 percentage of total breast STANDARD_DEVIATION 14.23 |
| Region of Enrollment United States | 99 participants | 98 participants | 197 participants |
| Sex: Female, Male Female | 99 Participants | 98 Participants | 197 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 / 99 | 0 / 98 |
| other Total, other adverse events | 1 / 99 | 6 / 98 |
| serious Total, serious adverse events | 0 / 99 | 0 / 98 |
Outcome results
Primary
Breast Density by Mammography
Area of FGBT in mammogram. The timepoints were combined and summed.
Time frame: baseline, and after year 1 and 2 of supplementation
Population: Three Soy Isoflavones participants had missing mammograms.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Soy Isoflavones | Breast Density by Mammography | 27.7 percentage of total breast | Standard Deviation 11.62 |
| Placebo | Breast Density by Mammography | 26.73 percentage of total breast | Standard Deviation 10.83 |
Primary
Fibroglandular Tissue in Total Breast (FGBT%)
Effects of 1 and 2 years of treatment with isoflavones on percent of changes in FGBT%.
Time frame: baseline, and after year 1 and 2 of supplementation
Population: Subjects with at least 1 treatment image.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Soy Isoflavones | Fibroglandular Tissue in Total Breast (FGBT%) | Baseline | 24.94 percentage of total breast tissue | Standard Deviation 14.11 |
| Soy Isoflavones | Fibroglandular Tissue in Total Breast (FGBT%) | Year 1 | 24.03 percentage of total breast tissue | Standard Deviation 15.34 |
| Soy Isoflavones | Fibroglandular Tissue in Total Breast (FGBT%) | Year 2 | 23.14 percentage of total breast tissue | Standard Deviation 14.58 |
| Placebo | Fibroglandular Tissue in Total Breast (FGBT%) | Baseline | 25.34 percentage of total breast tissue | Standard Deviation 14.93 |
| Placebo | Fibroglandular Tissue in Total Breast (FGBT%) | Year 1 | 25.82 percentage of total breast tissue | Standard Deviation 14.72 |
| Placebo | Fibroglandular Tissue in Total Breast (FGBT%) | Year 2 | 25.36 percentage of total breast tissue | Standard Deviation 13.38 |
Comparison: (FGBT% at 1 year of treatment minus FGBT% at baseline) divided by FGBT% at baseline.p-value: 0.071t-test, 2 sided
Comparison: (FGBT% at 2 year of treatment minus FGBT% at baseline) divided by FGBT% at baseline.p-value: 0.08t-test, 2 sided
Comparison: Intention to treatp-value: 0.019Regression, Linear
Secondary
Bone Mineral Density
Bone mineral density of hip, spine and whole body bone mineral density as measured by dual x-ray absorptiometry. The timepoints were combined and summed.
Time frame: one and two years after dietary supplement
Population: Intention to treat participants. Two placebo and one isoflavone subjects had breast images but no DXA tests.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Soy Isoflavones | Bone Mineral Density | Hip bone mineral density | 1.01 g/cm^2 | Standard Deviation 0.12 |
| Soy Isoflavones | Bone Mineral Density | Spine bone mineral density | 1.06 g/cm^2 | Standard Deviation 0.11 |
| Soy Isoflavones | Bone Mineral Density | Whole body bone mineral density | 1.08 g/cm^2 | Standard Deviation 0.09 |
| Placebo | Bone Mineral Density | Whole body bone mineral density | 1.07 g/cm^2 | Standard Deviation 0.09 |
| Placebo | Bone Mineral Density | Hip bone mineral density | 1.00 g/cm^2 | Standard Deviation 0.13 |
| Placebo | Bone Mineral Density | Spine bone mineral density | 1.06 g/cm^2 | Standard Deviation 0.11 |