Broccoli Sprout Extract in Treating Women Who Have Had a Mammogram and Breast Biopsy
RATIONALE: Broccoli sprout extract supplements may slow the growth of tumor cells or abnormal cells and may be an effective treatment for ductal carcinoma in situ and/or atypical ductal hyperplasia.
PURPOSE: This randomized phase II trial is studying how well broccoli sprout extract works in treating women with a diagnosis of breast cancer, ductal carcinoma in situ and/or atypical ductal hyperplasia.
|Breast Cancer Precancerous Condition||Dietary Supplement: broccoli sprout extract Other: placebo||Phase 2|
|Study Design:||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
|Official Title:||Sulforaphane: A Dietary Histone Deacetylase (HDAC) Inhibitor in Ductal Carcinoma in Situ (DCIS)|
- Change in Isothiocyanate in Urine Samples as Assessed at Baseline and After Completion of Study Therapy [ Time Frame: Baseline and end of study (up to 8 weeks) ]Isothiocyante including sulforaphane in micromolar (µM) concentration was measured following standard chemical measurement procedures and divided by the creatinine values in millimolar (mM) concentration.
- Change in Ki-67 as Assessed at Baseline and After Completion of Study Therapy [ Time Frame: Baseline and end of study (up to 8 weeks) ]Ki-67 was measured through immunohistochemistry method. A modified H-score was recorded, which involved semi-quantitative assessment of both staining intensity (graded as 1-3 with 1 representing weak staining, 2 moderate staining, and 3 strong staining) and percentage of positive cells. The range of the H-score was 0-300. The maximum score indicates the strongest expression, the minimum score indicates no expression of positive tumor area.
- Change in Histone Deacetylase (HDAC) Activity as Assessed in Peripheral Blood Mononuclear Cells (PBMC) at Baseline and After Completion of Study Therapy [ Time Frame: Baseline and End of Study (up to 8 weeks) ]PBMC HDAC activity was evaluated using the positive control, sodium butyrate.HDAC activity is expressed relative to PBMC protein content and negative control.
- Treatment Compliance [ Time Frame: Baseline and end of study (up to 8 weeks) ]For treatment compliance, participants who take >=80% of the prescribed pills will be considered to be treatment-compliant.
|Study Start Date:||August 2009|
|Study Completion Date:||December 2013|
|Primary Completion Date:||December 2013 (Final data collection date for primary outcome measure)|
Experimental: Sulforaphane Supplement
Patients receive oral broccoli sprout extract supplementation three times daily for 2-8 weeks in the absence of unacceptable toxicity.
Dietary Supplement: broccoli sprout extract
Placebo Comparator: Placebo
Patients receive oral placebo supplementation three times daily for 2-8 weeks in the absence of unacceptable toxicity.
- To determine the correlation between supplemental sulforaphane (broccoli sprout extract) dose and concentrations of sulforaphane and its metabolites in blood and urine samples from women positive for cancer, ductal carcinoma in situ and/or atypical ductal hyperplasia.
- To determine the effect of this supplement on biomarkers of prognosis in these patients.
- To determine the effect of this supplement on HDAC inhibition in peripheral blood cell and normal and cancerous breast tissue samples from these patients.
OUTLINE: Patients are randomized to 1 of 2 treatment arms.
- Sulforaphane Supplement: Patients receive oral broccoli sprout extract supplementation three times daily for 2-8 weeks in the absence of unacceptable toxicity.
- Placebo: Patients receive oral placebo supplementation three times daily for 2-8 weeks in the absence of unacceptable toxicity.
Blood and urine samples are collected at baseline and after completion of study treatment for laboratory biomarker studies. Patients scheduled to undergo surgery (mastectomy or lumpectomy) also undergo breast tissue sample collection at baseline and at the time of surgery. Samples are analyzed for sulforaphane metabolism (isothiocyanate levels), HDAC activity (acetylated histone expression), cell proliferation (Ki-67 index by IHC), and apoptosis (TUNEL assay).
Patients complete questionnaires at baseline and periodically during study about their dietary history, family history, cruciferous vegetable intake, adverse events, and dietary and medication changes.
After completion of study therapy, patients are followed at/around 30 days.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00843167
|United States, Oregon|
|Knight Cancer Institute at Oregon Health and Science University|
|Portland, Oregon, United States, 97239-3098|
|Principal Investigator:||Jackilen Shannon, PhD||OHSU Knight Cancer Institute|