Study to Evaluate the Effect of Sulforaphane in Broccoli Sprout Extract on Breast Tissue

Evaluating the Effect of Broccoli Sprouts (Sulforaphane) on Cellular Proliferation, an Intermediate Marker of Breast Cancer Risk

The purpose of this research is to examine the effect of a broccoli sprout preparation on specific factors in breast tissue that are related to breast cancer risk and to assess whether sulforaphane a key component of broccoli sprouts increases the levels of protective enzymes in breast tissue. In addition, the investigators will also examine how acceptable the broccoli sprouts preparation is to the study participants.

Study Overview

• Status: Completed
• Conditions: Breast Cancer
• Intervention / Treatment: Drug: Broccoli sprout extract; Drug: Mango juice

Detailed Description

A double-blind randomized Phase II chemoprevention trial of BSE versus placebo will be conducted in up to 35 women diagnosed with DCIS on core biopsy prior to their definitive surgery (study diagram below). The primary study endpoint will be a decrease in the mean proliferative rate measured by Ki67%.

Women diagnosed with DCIS on core or incisional/excisional biopsy scheduled for definitive surgery at Johns Hopkins Hospital will be recruited for this study. Participants will be placed on a cruciferous free diet for the 14 days prior to their surgical date and drink a randomized intervention beverage (mango juice with or without broccoli sprout extract). Additionally participants will provide 2 blood and 2 urine sample collections, report medication use and adverse events using prepared forms and complete a daily diet check list during the 14 day intervention. On the day of definitive breast surgery, 1-2 grams of breast tissue (including normal adjacent breast tissue) will be collected during surgery.

• Study Type: Interventional
• Enrollment (Actual): 34
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Baltimore, Maryland, United States, 21205
      • Johns Hopkins Medical Institution

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Female 18 + years of age
• Confirmed diagnosis of DCIS on core or excisional/incisional biopsy and scheduled for definitive surgery
• Pre or Post menopausal women reporting no use of hormone replacement therapy, tamoxifen or raloxifene within the prior 6 months to eligibility screening
• Agree to avoid cruciferous vegetable/condiment intake for 14 days
• Agree to sign an informed consent and allow use of some tissue (slides) from biopsy and definitive surgery for research purposes

Exclusion Criteria:

• Prior cancer diagnosis other than non-melanomatous skin cancer or cervical carcinoma in-situ
• Used hormone replacement therapy, tamoxifen or raloxifene within the past 6 months prior to eligibility screening
• Used antibiotics within 10 days prior to beginning cruciferous free diet (day -14 prior to surgery)
• Smoked within the past 12 months prior to eligibility screening;
• Active infection or inflammation of the breast at time of eligibility screening
• Has baseline comprehensive metabolic panel (CMP) [Glucose, Calcium, Albumin, Serum total protein (TP), Sodium, Potassium, Carbon dioxide, Chloride, Blood urea nitrogen (BUN), Creatinine, Alkaline phosphatase (ALP), Alanine amino transferase (AST), Aspartate amino transferase (SGOT), and Bilirubin], prothrombin time (PT) and , complete blood count (CBC) values that are 1.5 times in either direction the reported normal range

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Broccoli sprout extract; Patients will be randomized to 14 day intervention of broccoli sprout extract and mango juice consisting of a dose of 100 µmols of sulforaphane dissolved in 150 mL mango juice once a day.	Drug: Broccoli sprout extract; 100 µmols of sulforaphane (dissolvable); Drug: Mango juice; 150 mL of mango juice
Placebo Comparator: Mango juice; Patients will be randomized to 14 day intervention of 150 mL mango juice without broccoli sprout extract extract once a day.	Drug: Mango juice; 150 mL of mango juice

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Absolute Change in Mean Proliferative Rate Measured by Ki67%	Pathologists score the slides without knowledge of treatment assignment at the end of the study. All pre-post samples from one individual will be evaluated together. Quality control for these stains is performed routinely in the immunohistochemistry lab (using lymphoid tissue for Ki67). Initial scoring is performed where possible on a minimum of 3000 cells, by counting the number of positive cells divided by the total number of cells. DCIS lesions will be scored separately to adjacent normal tissue. The rationale for selecting Ki67 as a measure of cellular proliferation includes the robustness of the staining reaction, correlation with the S phase fraction of the cell cycle and mitotic index and that it can be successfully ascertained from core breast biopsies provided there is an adequate yield of epithelial cells. A negative value reflects a decrease in ki67 positive cells, therefore a decrease in cellular proliferation.	Change from baseline to 14 days post-intervention

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Phase II Protein Expression as Assessed by Change in Cytoprotective Enzyme Expression Within Tumor	Phase II protein expression of cytoprotective enzymes known to be modulated by sulforaphane in DCIS specimens. Cytoprotective enzymes measured (NQ01 and AKR1C1 expression) based on immunohistochemical analysis. Expression was categorized by the study pathologist based on percentage of cells expressing antibody on the slide.	Change from baseline to 14 days post-intervention

Collaborators and Investigators

• Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
• Collaborators: Breast Cancer Research Foundation
• Investigators: Principal Investigator: Kala Visvanathan, MD, Johns Hopkins Bloomberg School of Public Health and Sidney Kimmel Comprehensive Cancer Center

Study record dates

Study Major Dates

• Study Start: April 1, 2009
• Primary Completion (Actual): November 1, 2013
• Study Completion (Actual): November 1, 2013

Study Registration Dates

• First Submitted: September 22, 2009
• First Submitted That Met QC Criteria: September 22, 2009
• First Posted (Estimate): September 23, 2009

Study Record Updates

• Last Update Posted (Actual): November 21, 2018
• Last Update Submitted That Met QC Criteria: November 16, 2018
• Last Verified: November 1, 2018

More Information

Terms related to this study

• Keywords: Breast Cancer; Broccoli Sprout Extract
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms
• Other Study ID Numbers: J0822