Soy Protein and Breast Cancer Risk Reduction

Soybean Diet and Breast Density

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.

Study Overview

• Status: Completed
• Conditions: Breast Cancer
• Intervention / Treatment: Dietary supplement: soy milk; Dietary supplement: cow's milk

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.

• Study Type: Interventional
• Enrollment (Actual): 321
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Texas
    • Galveston, Texas, United States, 77555-0264
      • General Clinical Research Center, The University of Texas Medical Branch

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 30 years to 40 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: 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.	Dietary supplement: 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.; Other Names: Not applicable, research product
Placebo Comparator: 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.	Dietary supplement: 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.; Other Names: Not applicable, research product

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Baseline
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.	1 Year
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.	2 years
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.	Baseline
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.	1 Year
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.	2 years
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.	Baseline
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.	1 Year
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.	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Estradiol (pg/ml)	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.
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	4 measurements at baseline and once every three months after protein drink supplements for up to 2 years.
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	4 measurements at baseline and once every three months after protein drink supplements for up to 2 years.

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	4 measurements at baseline and once every three months after protein drink supplements for up to 2 years.
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	4 measurements at baseline and once every three months after protein drink supplements for up to 2 years.

Collaborators and Investigators

• Sponsor: The University of Texas Medical Branch, Galveston
• Collaborators: National Center for Research Resources (NCRR); U.S. Army Medical Research and Development Command
• Investigators: Principal Investigator: Lee-Jane W Lu, Ph.D., The University of Texas Medical Branch, Galveston, TX 77555

Publications and helpful links

General Publications

• Lu LJ, Nishino TK, Johnson RF, Nayeem F, Brunder DG, Ju H, Leonard MH, Grady JJ, Khamapirad T. Comparison of breast tissue measurements using magnetic resonance imaging, digital mammography and a mathematical algorithm. Phys Med Biol. 2012 Nov 7;57(21):6903-27. doi: 10.1088/0031-9155/57/21/6903. Epub 2012 Oct 9.
• Nayeem F, Anderson KE, Nagamani M, Grady JJ, Lu LJ. Alkaline phosphatase and percentage body fat predict circulating C-reactive protein in premenopausal women. Biomarkers. 2010 Dec;15(8):663-70. doi: 10.3109/1354750X.2010.509811. Epub 2010 Sep 29.

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2002
• Primary Completion (Actual): July 22, 2011
• Study Completion (Actual): May 29, 2023

Study Registration Dates

• First Submitted: September 9, 2005
• First Submitted That Met QC Criteria: September 13, 2005
• First Posted (Estimated): September 20, 2005

Study Record Updates

• Last Update Posted (Actual): January 23, 2024
• Last Update Submitted That Met QC Criteria: December 27, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Keywords: breast cancer; prevention; breast density; soy diet; ovarian hormones
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms
• Other Study ID Numbers: 02-422; Army's HSRRB log no. A-10926 (Other Identifier: USA MRMC Human Research Protection Office (HRPO)); UTMB GCRC 533 (Other Identifier: UTMB ITSCRC); DAMD17-01-1-0417 (Other Grant/Funding Number: USA MRMC); M01RR000073 (U.S. NIH Grant/Contract); 1UL1RR029876-01 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Will not share as this required financial resources.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No