Breast Cancer Prevention Studies

Randomized, placebo-controlled trial to test the effectiveness of supplemental SFN intake in altering HDAC activity and prognostic biomarkers in DCIS.

Sulforaphane Supplementation in Women Newly Diagnosed with DCIS.

This clinical trial is open to women who have been diagnosed with ductal carcinoma in situ (DCIS) or atypical ductal hyperplasia (ADH) or both. Participants are randomized to receive either the study supplement (BroccoMax®) or a placebo.

Eligible volunteers complete the following tasks:

- Provide permission for use of your breast biopsy tissue for this study

- Questionnaires: Diet History & Family History questionnaire; Cruciferous Vegetables      questionnaire;And few questions about the kinds of side effects subjects might be feeling while participating in the study.)

- Pregnancy urine test
- Blood draw for a measure of liver function (bilirubin) and research tests (about 3 tablespoons)
- Height, weight and blood pressure
- Nipple aspirate (using gentle suction to obtain a little fluid from breast)

Science: Significant advances in the diagnosis and medical management of ductal carcinoma in situ (DCIS) have reduced disease progression and improved long-term survival. However, it remains common for women to seek alternative therapies in an attempt to improve outcome. Sulforaphane (SFN), a phytochemical found in cruciferous vegetables has been demonstrated to inhibit breast cancer cell proliferation and enhance apoptosis, both in vitro and in vivo [1-5]. More recently, the role of gene silencing via EPIGENETIC alterations such as acetylation of histone structure has emerged an important factor in tumorigenesis [6, 7]. We have shown that SFN can inhibit histone deacetylase (HDAC) activity, augment levels of acetylated histones, increase acetylated histone H4 interactions with tumor suppressor gene promoters and induce caspase activity and apoptosis [8, 9]. Collectively, these results suggest that HDAC inhibition is a novel chemopreventive mechanism of SFN leading to decreased cell proliferation. We have demonstrated that dietary consumption of SFN limits tumor growth in animal models and decreases HDAC activity in human volunteers. Based on these studies, we are conducting a randomized, placebo-controlled trial to test the effectiveness of supplemental SFN intake in altering HDAC activity and prognostic biomarkers in DCIS.

We are recruiting women newly diagnosed with DCIS and/or atypical ductal hyperplasia (ADH) into a two-week randomized, double-blind, placebo-controlled trial of purified broccoli sprout supplementation. Women are identified at the time of diagnosis and are randomized to broccoli sprout capsules, consisting of 250mg of broccoli seed extract (30 mg sulforaphane glucosinolate) or placebo; two capsules three times daily. Primary endpoints include change in isothiocyanate in urine, blood and nipple aspirate fluid; breast tissue changes in cell proliferation, histone (H) 3 and H4 by immunohistochemistry and change in HDAC activity. All primary endpoints are measured at pre- and post-intervention.

Enrollment has very recently opened at Oregon Health & Science University and Kaiser Permanente Northwest. Fourteen of 60 women have successfully completed the trial.

1. Pledgie-Tracy A, Sobolewski MD, and Davidson NE. Mol Cancer Ther 2007;6(3):1013-1021.
2. Brandi G, Schiavano GF, Zaffaroni N, De Marco C, Paiardini M, Cervasi B, and Magnani M. J Nutr 2005;135(6):1503-1509.
3. Gill CI, Haldar S, Porter S, Matthews S, Sullivan S, Coulter J, McGlynn H, and Rowland I. Cancer Epidemiol Biomarkers Prev 2004;13(7):1199-1205.
4. Jackson SJ and Singletary KW. J Nutr 2004;134(9):2229-2236.
5. Johnston N. Drug Discov Today 2004;9(21):908.
6. Halkidou K, Cook S, Leung HY, Neal DE, and Robson CN. Eur Urol 2004;45(3):382-389; author reply 389.
7. Halkidou K, Gaughan L, Cook S, Leung HY, Neal DE, and Robson CN. Prostate 2004;59(2):177-189.
8. Myzak MC, Hardin K, Wang R, Dashwood RH, and Ho E. Carcinogenesis 2006;27(4):811-819.

9. Myzak MC, Karplus PA, Chung FL, and Dashwood RH. Cancer Res 2004;64(16):5767-5774.

Study Coordinator:
Paige Farris 503-220-8262 x54868  Email: farrisp@ohsu.edu

Omega-3 Fatty Acids and Prevention of DCIS and/or ADH: A Translational Approach

This was a pilot study to find out what effects fish oil has on DCIS and/or ADH. Omega-3 fatty acids, the fatty acids found in fish oil, have been shown in some population studies to reduce the risk of breast cancer. We are trying to understand how omega-3 fatty acids may change how breast cancer cells grow and reproduce. The study design was the same as the above SFN and DCIS study. A total of 17 women were enrolled in the study and analysis is still in process.