Soy Treatment for High-risk Women and DCIS Patients

Institution: University of Southern California
Investigator(s): Anna Wu, Ph.D. -
Award Cycle: 2009 (Cycle 15) Grant #: 15OB-0162 Award: $1,203,132
Award Type: Translational Research Award
Research Priorities
Etiology and Prevention>Prevention and Risk Reduction: ending the danger of breast cancer

Initial Award Abstract (2009)

There is accumulating evidence from observational epidemiologic studies that soy intake may be an attractive chemoprevention strategy for women with ductal carcinoma in situ (DCIS) or are at ‘high-risk’ for other reasons, including known BRCA1/BRCA2 mutations or a high (1.7 or greater) five-year Gail score. Current treatment modalities for DCIS patients are surgical resection (local excision or mastectomy), radiation therapy and tamoxifen therapy. Although a beneficial effect from tamoxifen for DCIS is well established, no more than about 25% of DCIS patients complete a 5-year course of tamoxifen, because of side effects or other reasons. While mastectomy and tamoxifen are prevention options for some high-risk women, these are not acceptable prevention strategies for the majority of women.

The overall objective of this translational project is to determine whether women with DCIS and other ‘high-risk’ women benefit from soy supplementation. We will evaluate whether there are significant beneficial changes from baseline in MRI volume, and markers of breast cell proliferation and apoptosis in the breast of ‘high-risk’ women who are randomized to soy compared to placebo for 1 year. Specifically, we will assess whether:
1) magnetic resonance imaging (MRI) volume (equivalent to 3-dimensional mammographic density) is reduced in high-risk women or those with DCIS who are supplemented daily with soy (25 g soy protein) compared to placebo (25 g milk protein) for 1 year.
2) cell proliferation and apoptosis, as measured by Ki67 and caspase 3 staining, respectively, of breast epithelial cells is altered with soy treatment.

We will offer soy/placebo agents to women who are not receiving other treatments. Women between the ages of 30 and 75, all racial/ethnic background, not regular (weekly) soy consumers or current users of exogenous hormonal therapy (e.g., OC, HT, soy estrogens) will be eligible. Mammogram, MRI, breast biopsy, blood and urine specimens, and anthropometric measures will be obtained at baseline and at the completion of 1 year of intervention. Blood/urine specimens and anthropometric breast measurements will be performed. Urinary soy isoflavone levels will be measured to assess compliance. For DCIS patients, the baseline and year 1 breast biopsies will be conducted on the unaffected breast. For high-risk women with DCIS, we will conduct the breast biopsies on the breast on the opposite side to their dominant arm. In pre-menopausal women, we will conduct the MRI, breast biopsies and collect blood/urine specimens around the mid-luteal phase of the menstrual cycle.

There are currently few treatment alternatives for women with DCIS and few non-invasive prevention strategies for ‘high-risk’ women. This research is aimed at addressing an important research need using soy, a dietary agent that is safe, affordable, and has been a staple in many Asian populations for centuries. Results we obtain from this proposed study are potentially applicable to women of all racial/ethnic backgrounds.

Final Report (2015)

The overall objective of this randomized, double-blind, placebo-controlled trial of soy/placebo tablets was to determine whether breast cancer patients and other ‘high-risk’ women benefit from soy supplementation. The intervention consisted of a daily dose of soy (containing 50 mg total isoflavones (as aglycone)) or placebo tablet. The duration of intervention was 1 year and subjects participated in a baseline and four follow-up visits at the end of 3, 6, 9, and 12 months of intervention. Mammogram, magnetic resonance imaging volume (MRI) (equivalent to 3-dimensional mammographic density), and breast biopsies were collected at baseline and at the end of month 12. Questionnaire data, anthropometric measurements, blood and urine specimens were collected at baseline and each of the 4 follow-up visits. We evaluated whether there were significant beneficial changes in association with soy supplementation in MRI volume, mammographic density, and markers of breast cell proliferation and apoptosis.

We obtained digital mammograms and breast MRI scans at baseline and after 12 months of daily soy (n=46) or placebo (n=49) tablet supplementation. The total breast area (MA) and the area of mammographic density (MD) on the mammogram was measured using a validated computer-assisted method, and mammographic density percent (MD%=100 x MD/MA) was determined. A well-tested computer algorithm was used to quantitatively measure the total breast volume (TBV) and fibroglandular tissue volume (FGV) on the breast MRI, and the FGV percent (FGV%=100 x FGV/TBV) was calculated. On the basis of plasma soy isoflavone levels, compliance was excellent. We found small decreases in MD% measured by the ratios of month 12 to baseline levels in the soy (0.95) and the placebo (0.87) groups; these changes did not differ between the soy/placebo treatments (P=0.38). We also found small decreases in FGV% in both the soy (0.90) and the placebo (0.92) groups; these changes did not differ between the treatments (P=0.48). Results were comparable in pre- and post-menopausal women, and in breast cancer patients and high-risk women. In summary, in this controlled intervention study in breast cancer patients or high-risk women, soy capsule intervention did not have any beneficial or adverse effects on breast tissue changes based on FGV% and MD% (Wu et al., in press).

Double-Blind Randomized 12-Month Soy Intervention Had No Effects onBreast MRI Fibroglandular Tissue Density or Mammographic Density

Soy isoflavones and breast cancer. doi: 10.1200/EdBook_AM.2013.33.102. PMID: 23714469
Periodical:American Society for Clinical Oncology
Index Medicus: Am Soc Clin Oncol
Authors: Wu AH, Lee E, Vigen C.
Yr: 2013 Vol: 33 Nbr: Abs: Pg:102-6