Clinical trial NCT00843167: Broccoli Sprout Extract in Treating Women Who Have Had a Mammogram and Breast Biopsy
Official title: Sulforaphane: A Dietary Histone Deacetylase (HDAC) Inhibitor in Ductal Carcinoma in Situ (DCIS)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Breast Cancer
Precancerous Condition
Keywords: mammography
biopsy
ductal breast carcinoma in situ
atypical ductal breast hyperplasia
Lead sponsor: OHSU Knight Cancer Institute
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2009-02-13
Enrollment: 54
Sex: FEMALE
Minimum age (years): 21
Maximum age (years): 120
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Change in Isothiocyanate in Urine Samples as Assessed at Baseline and After Completion of Study Therapy
timeFrame: Baseline and end of study (up to 8 weeks)
measure: Change in Ki-67 as Assessed at Baseline and After Completion of Study Therapy
timeFrame: Baseline and end of study (up to 8 weeks)
measure: Change in Histone Deacetylase (HDAC) Activity as Assessed in Peripheral Blood Mononuclear Cells (PBMC) at Baseline and After Completion of Study Therapy
timeFrame: Baseline and End of Study (up to 8 weeks)
Secondary outcomes:
measure: Treatment Compliance
timeFrame: Baseline and end of study (up to 8 weeks)
Other outcomes:
Locations:
city: Portland
country: United States
facility: Knight Cancer Institute at Oregon Health and Science University
state: Oregon
Study officials:
affiliation: OHSU Knight Cancer Institute
name: Jackilen Shannon, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Atwell LL, Zhang Z, Mori M, Farris P, Vetto JT, Naik AM, Oh KY, Thuillier P, Ho E, Shannon J. Sulforaphane Bioavailability and Chemopreventive Activity in Women Scheduled for Breast Biopsy. Cancer Prev Res (Phila). 2015 Dec;8(12):1184-1191. doi: 10.1158/1940-6207.CAPR-15-0119. Epub 2015 Oct 28.
citation: Zhang Z, Atwell LL, Farris PE, Ho E, Shannon J. Associations between cruciferous vegetable intake and selected biomarkers among women scheduled for breast biopsies. Public Health Nutr. 2016 May;19(7):1288-95. doi: 10.1017/S136898001500244X. Epub 2015 Sep 2.