Broccoli Sprout Extract in Treating Women Who Have Had a Mammogram and Breast Biopsy

Study Overview
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Brief Summary
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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.

Detailed Description
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OBJECTIVES: 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.

Official Title
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Sulforaphane: A Dietary Histone Deacetylase (HDAC) Inhibitor in Ductal Carcinoma in Situ (DCIS)

Conditions
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Breast Cancer, Precancerous Condition

Intervention / Treatment
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* Dietary Supplement: broccoli sprout extract
* Other: placebo


Participation Criteria
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Eligibility Criteria
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INCLUSION CRITERIA: Diagnostic mammogram English speaking EXCLUSION CRITERIA: Pregnancy (as determined by urine human chorionic gonadotropin (hCG) test) No biopsy referral after diagnostic mammogram Patient reported breast feeding Significant active medical illness which in the opinion of the investigator would preclude protocol treatment History of or active liver disease or baseline total bilirubin greater than institutional upper limit of normal Patient reported allergy or sensitivity to cruciferous vegetables Use of oral antibiotics within three months prior to randomization Oral steroid therapy at enrollment Current therapy with valproate acid or SAHA Current use of nutrient supplements or herbal remedies containing sulforaphane and unwillingness or inability to quit 72 hours prior to randomization and for the duration of the trial Radiation for currently-diagnosed disease prior to or during study supplementation Chemotherapy for currently-diagnosed disease prior to or during study supplementation

Ages Eligible for Study
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Minimum Age: 21 Years
Maximum Age: 120 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Sulforaphane Supplement<br>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<br>* Given orally<br>|
| Placebo Comparator: Placebo<br>Patients receive oral placebo supplementation three times daily for 2-8 weeks in the absence of unacceptable toxicity. | Other: placebo<br>* Given orally<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Isothiocyanate in Urine Samples as Assessed at Baseline and After Completion of Study Therapy | Isothiocyante including sulforaphane in micromolar (µM) concentration was measured following standard chemical measurement procedures and divided by the creatinine values in millimolar (mM) concentration. | Baseline and end of study (up to 8 weeks) | 
| Change in Ki-67 as Assessed at Baseline and After Completion of Study Therapy | 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. | Baseline and end of study (up to 8 weeks) | 
| Change in Histone Deacetylase (HDAC) Activity as Assessed in Peripheral Blood Mononuclear Cells (PBMC) at Baseline and After Completion of Study Therapy | PBMC HDAC activity was evaluated using the positive control, sodium butyrate.HDAC activity is expressed relative to PBMC protein content and negative control. | Baseline and End of Study (up to 8 weeks) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Treatment Compliance | For treatment compliance, participants who take >=80% of the prescribed pills will be considered to be treatment-compliant. | Baseline and end of study (up to 8 weeks) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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mammography, biopsy, ductal breast carcinoma in situ, atypical ductal breast hyperplasia