Breast Cancer
Conditions
Keywords
Broccoli Sprout Extract, Breast Cancer
Brief summary
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.
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.
Interventions
100 µmols of sulforaphane (dissolvable)
DRUGMango juice
150 mL of mango juice
Sponsors
Breast Cancer Research Foundation
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Absolute Change in Mean Proliferative Rate Measured by Ki67% | Change from baseline to 14 days post-intervention | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Phase II Protein Expression as Assessed by Change in Cytoprotective Enzyme Expression Within Tumor | Change from baseline to 14 days post-intervention | 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Broccoli Sprout Extract and Mango Juice Patients will be randomized to 14 day intervention of broccoli sprout extract consisting of a consistent dose of sulforaphane dissolved in mango juice compared to a placebo preparation of mango juice alone. All women will be on a cruciferous free diet for the duration of the study (14 days).
Broccoli sprout extract (sulforaphane): Women newly diagnosed with DCIS on core biopsy prior to definitive surgery will be randomized to either a prepartion of broccoli sprout extract and mango juice or a placebo preparation of mango juice alone. All women will be on a cruciferous free diet for the duration of the study (14 days) and complete a daily dietary check list. Twelve hour urine collections and blood samples will be collected at various time points during the study. Acceptability of the 14 day dose will be evaluated by monitoring indices of compliance, including urinary measurements of ITC excretion, the daily food check list and a questionnaire administered at the end of the study. | 15 |
| Mango Juice Patients will be randomized to 14 day intervention of Mango juice without broccoli extract. All women will be on a cruciferous free diet for the duration of the study (14 days).
Mango juice: Women newly diagnosed with DCIS on core biopsy prior to definitive surgery will be randomized to either a prepartion of broccoli sprout extract and mango juice or a placebo preparation of mango juice alone. All women will be on a cruciferous free diet for the duration of the study (14 days) and complete a daily dietary check list. Twelve hour urine collections and blood samples will be collected at various time points during the study. Acceptability of the 14 day dose will be evaluated by monitoring indices of compliance, including urinary measurements of ITC excretion, the daily food check list and a questionnaire administered at the end of the study. | 15 |
| Total | 30 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Pregnancy | 0 | 1 |
| Overall Study | Preop values out of acceptable range | 1 | 1 |
| Overall Study | Surgery date change | 1 | 0 |
Baseline characteristics
| Characteristic | Mango Juice | Broccoli Sprout Extract and Mango Juice | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 3 Participants | 2 Participants | 5 Participants |
| Age, Categorical Between 18 and 65 years | 12 Participants | 13 Participants | 25 Participants |
| Age, Continuous | 54 years | 52 years | 53 years |
| Region of Enrollment United States | 15 Participants | 15 Participants | 30 Participants |
| Sex: Female, Male Female | 15 Participants | 15 Participants | 30 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 15 | 0 / 15 |
| other Total, other adverse events | 9 / 15 | 9 / 15 |
| serious Total, serious adverse events | 0 / 15 | 0 / 15 |
Outcome results
Primary
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.
Time frame: Change from baseline to 14 days post-intervention
Population: All participants who completed the 14-day intervention on either study arm were included in analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Broccoli Sprout Extract and Mango Juice | Absolute Change in Mean Proliferative Rate Measured by Ki67% | -1.15 percentage of Ki67 | Standard Deviation 2.08 |
| Mango Juice Without Extract | Absolute Change in Mean Proliferative Rate Measured by Ki67% | 4 percentage of Ki67 | Standard Deviation 17.08 |
p-value: 0.32Wilcoxon (Mann-Whitney)
Secondary
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.
Time frame: Change from baseline to 14 days post-intervention
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Broccoli Sprout Extract and Mango Juice | Phase II Protein Expression as Assessed by Change in Cytoprotective Enzyme Expression Within Tumor | NQO1 | 730.98 % change of expression in tumor cells | Standard Deviation 2411.96 |
| Broccoli Sprout Extract and Mango Juice | Phase II Protein Expression as Assessed by Change in Cytoprotective Enzyme Expression Within Tumor | AKR1C1 | 62.1 % change of expression in tumor cells | Standard Deviation 312.99 |
| Mango Juice Without Extract | Phase II Protein Expression as Assessed by Change in Cytoprotective Enzyme Expression Within Tumor | AKR1C1 | 867.4 % change of expression in tumor cells | Standard Deviation 2097.8 |
| Mango Juice Without Extract | Phase II Protein Expression as Assessed by Change in Cytoprotective Enzyme Expression Within Tumor | NQO1 | 6.34 % change of expression in tumor cells | Standard Deviation 30.12 |