Breast Cancer
Conditions
Brief summary
This randomized phase II trial is studying how well genistein works in preventing breast cancer in women at high risk for breast cancer. Chemoprevention is the use of certain drugs to keep cancer from forming, growing, or coming back. The use of genistein may prevent breast cancer in women at high risk for breast cancer.
Detailed description
PRIMARY OBJECTIVE: I. Determine the effect of genistein on the proliferation of breast epithelial cells obtained by fine needle aspiration (FNA), as measured by Ki-67 labeling index, in women who are at high risk for breast cancer. SECONDARY OBJECTIVE: I. Determine the effect of this drug on cellular and molecular parameters using epithelial cells obtained by FNA, nipple aspirate fluid, and blood from these patients. OUTLINE: This is a randomized, double-blind, placebo-controlled study. Patients are stratified according to menopausal status (premenopausal vs postmenopausal) and history of breast cancer (no history of breast cancer vs history of estrogen receptor \[ER\] positive breast cancer vs history of ER negative breast cancer). Patients are randomized to 1 of 2 treatment arms. ARM I: Patients receive oral genistein once daily. ARM II: Patients receive oral placebo once daily. In both arms, treatment continues for up to 6 months in the absence of unacceptable toxicity. After completion of study treatment, patients are followed at 30-37 days.
Interventions
DRUGplacebo
Given orally
DRUGgenistein
Given orally
OTHERlaboratory biomarker analysis
Correlative studies
Sponsors
National Cancer Institute (NCI)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
FEMALE
Age
25 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* No known soy intolerance * At increased risk of developing breast cancer in \>= 1 previously unaffected breast, as defined by any of the following: * Estimated 5-year risk of developing breast cancer using the Gail model, as defined by 1 of the following: * Gail score \>= 1.66% * Gail score \>= 0.1% for women age 20-29 years * Gail score \>= 1.0% for women age 30-39 years * Estimated 5-year risk of developing breast cancer using the Claus model: * Claus score \>= 1.66% * Claus score \>= 0.1% for women age 20-29 years * Claus score \>= 1.0% for women age 30-39 years * Prior diagnosis of unilateral in situ or invasive breast cancer OR history of atypical hyperplasia, BRCA 1 and/or BRCA 2 positivity * History of lobular carcinoma in situ * No evidence of breast cancer, as determined by a negative mammogram within the past 6 months and a history and physical * No previously diagnosed breast cancer unless all systemic therapy (including endocrine therapy) was completed at least 1 year ago * Pre- or postmenopausal * ECOG performance status 0-1 * Hemoglobin \> 10.0 g/dL * Platelet count \> 100,000/mm\^3 * Absolute neutrophil count \> 1,000/mm\^3 * Creatinine \< 2.0 mg/dL * SGPT \< 82 U/L * SGOT \< 68 U/L * Bilirubin \< 3 mg/dL\* \[Note: \* Patients with a higher level of bilirubin due to a familial metabolism may be eligible at the discretion of the investigator\] * Life expectancy \> 2 years * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective barrier contraception * Must be willing to keep a dietary diary * No venous thrombosis within the past year * No unrecognized or poorly controlled thyroid disease * No other cancer within the past 5 years except nonmelanomatous skin cancer or noninvasive cervical cancer * No other medical condition that, in the opinion of the investigator, would jeopardize either the patient or the integrity of the data obtained * None of the following for \>= 2 weeks before the first random fine needle aspiration and during study participation: * Oral contraceptives * Soy supplements * High soy-containing foods * Fish oil supplements * Multivitamins * Vitamins C and E * Daily aspirin or nonsteroidal * Anti-inflammatory drugs * No other concurrent investigational agents * No concurrent warfarin or other blood thinners * Female patient
Exclusion criteria
Women previously diagnosed with breast cancer will not be eligible unless all systemic therapy (including endocrine therapy) was completed at least one year previously * Currently pregnant, or planning to become pregnant during the study period * History of venous thrombosis within past year * Medical conditions, which, in the opinion of the investigators would jeopardize either the patient or the integrity of the data obtained * History of other cancer within the past five years, excluding non-melanomatous skin cancer, and non-invasive cervical cancer * Known soy intolerance * Unrecognized or uncontrolled thyroid disease, subjects may be on synthroid, but thyroid function must be in normal range or the patient's physician must document that the patient's thyroid is controlled. * Currently receiving any other investigational agents * Currently on coumadin, or other blood thinners * History of breast augmentation implants. * Rusults from patients who have \<4000 epithelial cells in either the first or the second random Fine-needle aspiration (rFNA) will not be included in the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Breast Epithelial Cell Proliferation as Measured by Ki-67 Labeling | 6 months - baseline | Breast epithelial tissue samples are used to measure the expression of the cell proliferation marker Ki-67, by counting the percentage of positive MIB-1 immunostained cells, denoted the Ki-67 labeling index. Mean change in the Ki-67 labeling index is assessed from baseline to 6 month follow up. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Cytomorphologic Assessment of Atypia and Spectral Imaging Analysis of Atypica Features in Epithelial Cells. | 6 months - baseline | Cytologic atypia evaluation was performed on Papanicolau stained Thin Prep slides using standard criteria, which were also used for spectral spatial imaging. Cell clusters were used to generate image stacks with the Nuance LCTF-based imaging system (CRI Inc). The image data was collected as percent pixels assigned as atypical. Mean change in the percent pixels assigned atypical is assessed from baseline to 6 month follow up. |
| Breast Endocrine Environment Measured in Nipple Aspiration Fluid (NAF): Estradiol | 6 months - baseline | Mean change in concentration of estradiol measured in nipple aspiration fluid assessed from baseline to 6 month follow up. |
| Monitor Drug Delivery by Measuring Plasma Genistein by HPLC | 6 months - baseline | Drug delivery is measured be concentration of genistein in plasma using High Performance Liquid Chromatography (HPLC). Mean change in concentration of plasma genistein is assessed from baseline to 6 month follow up. |
| Measurement of Change in Concentration of Epidermal Growth Factor (EGF) Found in Nipple Aspirate Fluid (NAF) | 6 months - baseline | Mean change in the concentration of EGF found in nipple aspirate fluid is assessed from baseline to 6 month follow up. |
| Breast Endocrine Environment Measured in Nipple Aspiration Fluid (NAF): Cathepsin D | 6 months - baseline | Mean change in concentration of Cathepsin D measured in nipple aspiration fluid assessed from baseline to 6 month follow up. |
| Breast Endocrine Environment Measured in Nipple Aspiration Fluid (NAF): ps2 | 6 month - baseline | Mean change in concentration of protein ps2 measured in nipple aspiration fluid assessed from baseline to 6 month follow up. |
| Plasma Concentration of Sex Hormone Binding Globulin (SHBG) | 6 months - baseline | — |
Countries
United States
Participant flow
Recruitment details
Study opened to accrual January 6, 2006. Study closed to accrual August 27, 2008. Subjects were recruited from the Lynn Sage Comprehensive Breast Center of Northwestern University, through ads on public transportation, through website and flyer distributions.
Pre-assignment details
Potential subjects underwent a 2 week washout period of soy products, vitamins, and daily aspirin prior to a screening random fine need aspiration (rFNA) of the breast(s). Subjects for which 4,000 or more epithelial cells were obtained the first or second rFNA were considered eligible for study participation.
Participants by arm
| Arm | Count |
|---|---|
| Arm A Patients receive oral genistein once daily for up to 6 months. | 62 |
| Arm B Patients receive oral placebo once daily for up to 6 months. | 64 |
| Total | 126 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Post Intervention rFNA | <4000 Epithelial Cells | 6 | 5 |
| Pre-Intervention rFNA Through Follow-Up | Adverse Event | 1 | 2 |
| Pre-Intervention rFNA Through Follow-Up | ConMeds | 1 | 0 |
| Pre-Intervention rFNA Through Follow-Up | Lost to Follow-up | 1 | 1 |
| Pre-Intervention rFNA Through Follow-Up | Medical Contraindication | 1 | 0 |
| Pre-Intervention rFNA Through Follow-Up | Non Compliant | 0 | 1 |
| Pre-Intervention rFNA Through Follow-Up | Physician Decision | 3 | 1 |
| Pre-Intervention rFNA Through Follow-Up | Withdrawal by Subject | 0 | 5 |
Baseline characteristics
| Characteristic | Arm A | Arm B | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 1 Participants | 1 Participants | 2 Participants |
| Age, Categorical Between 18 and 65 years | 61 Participants | 63 Participants | 124 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants | 2 Participants | 4 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 60 Participants | 62 Participants | 122 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Gender Female | 62 Participants | 64 Participants | 126 Participants |
| Gender Male | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 7 Participants | 12 Participants | 19 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 54 Participants | 52 Participants | 106 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 50 / 62 | 56 / 64 |
| serious Total, serious adverse events | 6 / 62 | 1 / 64 |
Outcome results
Primary
Change in Breast Epithelial Cell Proliferation as Measured by Ki-67 Labeling
Breast epithelial tissue samples are used to measure the expression of the cell proliferation marker Ki-67, by counting the percentage of positive MIB-1 immunostained cells, denoted the Ki-67 labeling index. Mean change in the Ki-67 labeling index is assessed from baseline to 6 month follow up.
Time frame: 6 months - baseline
Population: Participants who had more than 4,000 epithelial cells in rFNA samples at both baseline and 6 month follow up, met the criteria for compliance, and were available for evaluation of Ki-67 labeling index at both time points. Analysis performed by menopause and cancer status.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Arm A (Genistein) | Change in Breast Epithelial Cell Proliferation as Measured by Ki-67 Labeling | Premenopausal without cancer | 1.171 Ki-67 labeling index | Standard Deviation 2.922 |
| Arm A (Genistein) | Change in Breast Epithelial Cell Proliferation as Measured by Ki-67 Labeling | Postmenopausal with ER+ Cancer | -.418 Ki-67 labeling index | Standard Deviation 0.191 |
| Arm A (Genistein) | Change in Breast Epithelial Cell Proliferation as Measured by Ki-67 Labeling | Premonopausal with ER- Cancer | -.335 Ki-67 labeling index | Standard Deviation 0.93 |
| Arm A (Genistein) | Change in Breast Epithelial Cell Proliferation as Measured by Ki-67 Labeling | Postmenopausal Without Cancer | -.092 Ki-67 labeling index | Standard Deviation 0.525 |
| Arm A (Genistein) | Change in Breast Epithelial Cell Proliferation as Measured by Ki-67 Labeling | Postmenopausal with ER- Cancer | .325 Ki-67 labeling index | Standard Deviation 0.343 |
| Arm A (Genistein) | Change in Breast Epithelial Cell Proliferation as Measured by Ki-67 Labeling | Premenopausal with ER+ Cancer | -.387 Ki-67 labeling index | Standard Deviation 0.806 |
| Arm B (Placebo) | Change in Breast Epithelial Cell Proliferation as Measured by Ki-67 Labeling | Postmenopausal with ER- Cancer | .289 Ki-67 labeling index | Standard Deviation 0.541 |
| Arm B (Placebo) | Change in Breast Epithelial Cell Proliferation as Measured by Ki-67 Labeling | Premenopausal with ER+ Cancer | -.204 Ki-67 labeling index | Standard Deviation 1.329 |
| Arm B (Placebo) | Change in Breast Epithelial Cell Proliferation as Measured by Ki-67 Labeling | Premenopausal without cancer | 0.557 Ki-67 labeling index | Standard Deviation 1.546 |
| Arm B (Placebo) | Change in Breast Epithelial Cell Proliferation as Measured by Ki-67 Labeling | Postmenopausal Without Cancer | -.122 Ki-67 labeling index | Standard Deviation 0.735 |
| Arm B (Placebo) | Change in Breast Epithelial Cell Proliferation as Measured by Ki-67 Labeling | Postmenopausal with ER+ Cancer | -.461 Ki-67 labeling index | Standard Deviation 0.458 |
| Arm B (Placebo) | Change in Breast Epithelial Cell Proliferation as Measured by Ki-67 Labeling | Premonopausal with ER- Cancer | .873 Ki-67 labeling index | Standard Deviation 0.786 |
Secondary
Breast Endocrine Environment Measured in Nipple Aspiration Fluid (NAF): Cathepsin D
Mean change in concentration of Cathepsin D measured in nipple aspiration fluid assessed from baseline to 6 month follow up.
Time frame: 6 months - baseline
Population: NAF collection was attempted on all 98 participants and was successful in 46 at both time points. Mean change in Cathespin D concentration available for 44 participants. Analysis performed by menopause and cancer status.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Arm A (Genistein) | Breast Endocrine Environment Measured in Nipple Aspiration Fluid (NAF): Cathepsin D | post menopausal with ER- cancer | -3105.29 mg/ml | Standard Deviation 6764.2 |
| Arm A (Genistein) | Breast Endocrine Environment Measured in Nipple Aspiration Fluid (NAF): Cathepsin D | post menopausal without cancer | 3362.326 mg/ml | Standard Deviation 9545.02 |
| Arm A (Genistein) | Breast Endocrine Environment Measured in Nipple Aspiration Fluid (NAF): Cathepsin D | pre menopausal with ER- cancer | 1800.40 mg/ml | Standard Deviation 0 |
| Arm A (Genistein) | Breast Endocrine Environment Measured in Nipple Aspiration Fluid (NAF): Cathepsin D | Pre menopausal without Cancer | -4904.09 mg/ml | Standard Deviation 28128.12 |
| Arm B (Placebo) | Breast Endocrine Environment Measured in Nipple Aspiration Fluid (NAF): Cathepsin D | Pre menopausal without Cancer | 486.56 mg/ml | Standard Deviation 40420.5 |
| Arm B (Placebo) | Breast Endocrine Environment Measured in Nipple Aspiration Fluid (NAF): Cathepsin D | pre menopausal with ER- cancer | 29337.79 mg/ml | Standard Deviation 36645.39 |
| Arm B (Placebo) | Breast Endocrine Environment Measured in Nipple Aspiration Fluid (NAF): Cathepsin D | post menopasual with ER+ caner | -3961.16 mg/ml | Standard Deviation 1295.29 |
| Arm B (Placebo) | Breast Endocrine Environment Measured in Nipple Aspiration Fluid (NAF): Cathepsin D | pre menopausal with ER+ cancer | -6218.25 mg/ml | Standard Deviation 0 |
| Arm B (Placebo) | Breast Endocrine Environment Measured in Nipple Aspiration Fluid (NAF): Cathepsin D | post menopausal without cancer | -1774.72 mg/ml | Standard Deviation 17644.27 |
Secondary
Breast Endocrine Environment Measured in Nipple Aspiration Fluid (NAF): Estradiol
Mean change in concentration of estradiol measured in nipple aspiration fluid assessed from baseline to 6 month follow up.
Time frame: 6 months - baseline
Population: NAF collection was attempted on all 98 participants and was successful in 46 at both time points. Mean change in estradiol concentration available for 40 participants. Analysis performed by menopause and cancer status.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Arm A (Genistein) | Breast Endocrine Environment Measured in Nipple Aspiration Fluid (NAF): Estradiol | Postmenopausal with ER- Cancer | 2251.92 pg/ml | Standard Deviation 292.66 |
| Arm A (Genistein) | Breast Endocrine Environment Measured in Nipple Aspiration Fluid (NAF): Estradiol | Postmenopausal Without Cancer | -354.39 pg/ml | Standard Deviation 643.44 |
| Arm A (Genistein) | Breast Endocrine Environment Measured in Nipple Aspiration Fluid (NAF): Estradiol | Premenopausal with ER- Cancer | -129.58 pg/ml | Standard Deviation 0 |
| Arm A (Genistein) | Breast Endocrine Environment Measured in Nipple Aspiration Fluid (NAF): Estradiol | Premenopausal without cancer | -591.81 pg/ml | Standard Deviation 992.24 |
| Arm B (Placebo) | Breast Endocrine Environment Measured in Nipple Aspiration Fluid (NAF): Estradiol | Premenopausal without cancer | 6.31 pg/ml | Standard Deviation 394.74 |
| Arm B (Placebo) | Breast Endocrine Environment Measured in Nipple Aspiration Fluid (NAF): Estradiol | Postmenopausal with ER+ Cancer | -497.3 pg/ml | Standard Deviation 0 |
| Arm B (Placebo) | Breast Endocrine Environment Measured in Nipple Aspiration Fluid (NAF): Estradiol | Premenopausal with ER- Cancer | -36.38 pg/ml | Standard Deviation 16.42 |
| Arm B (Placebo) | Breast Endocrine Environment Measured in Nipple Aspiration Fluid (NAF): Estradiol | Postmenopausal Without Cancer | 925.83 pg/ml | Standard Deviation 955.71 |
Secondary
Breast Endocrine Environment Measured in Nipple Aspiration Fluid (NAF): ps2
Mean change in concentration of protein ps2 measured in nipple aspiration fluid assessed from baseline to 6 month follow up.
Time frame: 6 month - baseline
Population: NAF collection was attempted on all 98 participants and was successful in 46 at both time points. Mean change in ps2 concentration available for 44 participants. Analysis performed by menopause and cancer status.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Arm A (Genistein) | Breast Endocrine Environment Measured in Nipple Aspiration Fluid (NAF): ps2 | Post menopausal with ER- cancer | -28.00 ng/ml | Standard Deviation 41.85 |
| Arm A (Genistein) | Breast Endocrine Environment Measured in Nipple Aspiration Fluid (NAF): ps2 | Post menopausal without cancer | -14.17 ng/ml | Standard Deviation 32.4 |
| Arm A (Genistein) | Breast Endocrine Environment Measured in Nipple Aspiration Fluid (NAF): ps2 | Pre menopausal with ER- cancer | -16.68 ng/ml | Standard Deviation 0 |
| Arm A (Genistein) | Breast Endocrine Environment Measured in Nipple Aspiration Fluid (NAF): ps2 | Pre menopausal without Cancer | -20.49 ng/ml | Standard Deviation 54.3 |
| Arm B (Placebo) | Breast Endocrine Environment Measured in Nipple Aspiration Fluid (NAF): ps2 | Pre menopausal without Cancer | 12.17 ng/ml | Standard Deviation 29.74 |
| Arm B (Placebo) | Breast Endocrine Environment Measured in Nipple Aspiration Fluid (NAF): ps2 | Pre menopausal with ER- cancer | 4.69 ng/ml | Standard Deviation 23.75 |
| Arm B (Placebo) | Breast Endocrine Environment Measured in Nipple Aspiration Fluid (NAF): ps2 | Post menopasual with ER+ caner | -61.06 ng/ml | Standard Deviation 10.06 |
| Arm B (Placebo) | Breast Endocrine Environment Measured in Nipple Aspiration Fluid (NAF): ps2 | Pre menopausal with ER+ cancer | -31.46 ng/ml | Standard Deviation 0 |
| Arm B (Placebo) | Breast Endocrine Environment Measured in Nipple Aspiration Fluid (NAF): ps2 | Post menopausal without cancer | -6.10 ng/ml | Standard Deviation 65.38 |
Secondary
Change in Cytomorphologic Assessment of Atypia and Spectral Imaging Analysis of Atypica Features in Epithelial Cells.
Cytologic atypia evaluation was performed on Papanicolau stained Thin Prep slides using standard criteria, which were also used for spectral spatial imaging. Cell clusters were used to generate image stacks with the Nuance LCTF-based imaging system (CRI Inc). The image data was collected as percent pixels assigned as atypical. Mean change in the percent pixels assigned atypical is assessed from baseline to 6 month follow up.
Time frame: 6 months - baseline
Population: Analysis performed by menopause and cancer status.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Arm A (Genistein) | Change in Cytomorphologic Assessment of Atypia and Spectral Imaging Analysis of Atypica Features in Epithelial Cells. | Postmenopausal with ER+ Cancer | -3.00 Percent pixels | Standard Deviation 2.12 |
| Arm A (Genistein) | Change in Cytomorphologic Assessment of Atypia and Spectral Imaging Analysis of Atypica Features in Epithelial Cells. | Postmenopausal with ER- Cancer | -1.25 Percent pixels | Standard Deviation 0.96 |
| Arm A (Genistein) | Change in Cytomorphologic Assessment of Atypia and Spectral Imaging Analysis of Atypica Features in Epithelial Cells. | Postmenopausal Without Cancer | -0.50 Percent pixels | Standard Deviation 1.87 |
| Arm A (Genistein) | Change in Cytomorphologic Assessment of Atypia and Spectral Imaging Analysis of Atypica Features in Epithelial Cells. | Premenopausal with ER- Cancer | 0.50 Percent pixels | Standard Deviation 0.71 |
| Arm A (Genistein) | Change in Cytomorphologic Assessment of Atypia and Spectral Imaging Analysis of Atypica Features in Epithelial Cells. | Premenopausal with ER+ Cancer | 0.50 Percent pixels | Standard Deviation 1.29 |
| Arm A (Genistein) | Change in Cytomorphologic Assessment of Atypia and Spectral Imaging Analysis of Atypica Features in Epithelial Cells. | Premenopausal without cancer | 0.17 Percent pixels | Standard Deviation 2.42 |
| Arm B (Placebo) | Change in Cytomorphologic Assessment of Atypia and Spectral Imaging Analysis of Atypica Features in Epithelial Cells. | Premenopausal with ER+ Cancer | -0.75 Percent pixels | Standard Deviation 0.96 |
| Arm B (Placebo) | Change in Cytomorphologic Assessment of Atypia and Spectral Imaging Analysis of Atypica Features in Epithelial Cells. | Postmenopausal with ER+ Cancer | -.40 Percent pixels | Standard Deviation 0.89 |
| Arm B (Placebo) | Change in Cytomorphologic Assessment of Atypia and Spectral Imaging Analysis of Atypica Features in Epithelial Cells. | Premenopausal with ER- Cancer | 0 Percent pixels | Standard Deviation 0 |
| Arm B (Placebo) | Change in Cytomorphologic Assessment of Atypia and Spectral Imaging Analysis of Atypica Features in Epithelial Cells. | Postmenopausal with ER- Cancer | 0 Percent pixels | Standard Deviation 0 |
| Arm B (Placebo) | Change in Cytomorphologic Assessment of Atypia and Spectral Imaging Analysis of Atypica Features in Epithelial Cells. | Premenopausal without cancer | 0.95 Percent pixels | Standard Deviation 2.18 |
| Arm B (Placebo) | Change in Cytomorphologic Assessment of Atypia and Spectral Imaging Analysis of Atypica Features in Epithelial Cells. | Postmenopausal Without Cancer | 0 Percent pixels | Standard Deviation 1.45 |
Secondary
Measurement of Change in Concentration of Epidermal Growth Factor (EGF) Found in Nipple Aspirate Fluid (NAF)
Mean change in the concentration of EGF found in nipple aspirate fluid is assessed from baseline to 6 month follow up.
Time frame: 6 months - baseline
Population: NAF collection was attempted on all 98 participants and was successful in 46 at both time points. Mean change in EGF concentration available for 43 participants. Analysis performed by menopause and cancer status.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Arm A (Genistein) | Measurement of Change in Concentration of Epidermal Growth Factor (EGF) Found in Nipple Aspirate Fluid (NAF) | Postmenopausal with ER- Cancer | -133.07 ng/ml | Standard Deviation 308.28 |
| Arm A (Genistein) | Measurement of Change in Concentration of Epidermal Growth Factor (EGF) Found in Nipple Aspirate Fluid (NAF) | Postmenopausal without cancer | 201.05 ng/ml | Standard Deviation 380.72 |
| Arm A (Genistein) | Measurement of Change in Concentration of Epidermal Growth Factor (EGF) Found in Nipple Aspirate Fluid (NAF) | Premenopausal with ER- Cancer | -93.23 ng/ml | Standard Deviation 0 |
| Arm A (Genistein) | Measurement of Change in Concentration of Epidermal Growth Factor (EGF) Found in Nipple Aspirate Fluid (NAF) | Premenopausal without cancer | -9.16 ng/ml | Standard Deviation 296.55 |
| Arm B (Placebo) | Measurement of Change in Concentration of Epidermal Growth Factor (EGF) Found in Nipple Aspirate Fluid (NAF) | Premenopausal without cancer | -9.26 ng/ml | Standard Deviation 175.57 |
| Arm B (Placebo) | Measurement of Change in Concentration of Epidermal Growth Factor (EGF) Found in Nipple Aspirate Fluid (NAF) | Premenopausal with ER- Cancer | 37.38 ng/ml | Standard Deviation 69.11 |
| Arm B (Placebo) | Measurement of Change in Concentration of Epidermal Growth Factor (EGF) Found in Nipple Aspirate Fluid (NAF) | Postmenopausal with ER+ Cancer | -197.8 ng/ml | Standard Deviation 16.01 |
| Arm B (Placebo) | Measurement of Change in Concentration of Epidermal Growth Factor (EGF) Found in Nipple Aspirate Fluid (NAF) | Premenopausal with ER+ Cancer | 20.63 ng/ml | Standard Deviation 0 |
| Arm B (Placebo) | Measurement of Change in Concentration of Epidermal Growth Factor (EGF) Found in Nipple Aspirate Fluid (NAF) | Postmenopausal without cancer | -38.74 ng/ml | Standard Deviation 226.18 |
Secondary
Monitor Drug Delivery by Measuring Plasma Genistein by HPLC
Drug delivery is measured be concentration of genistein in plasma using High Performance Liquid Chromatography (HPLC). Mean change in concentration of plasma genistein is assessed from baseline to 6 month follow up.
Time frame: 6 months - baseline
Population: Analysis performed by menopause and cancer status.
| Arm | Measure | Group | Value (MEDIAN) | Dispersion |
|---|---|---|---|---|
| Arm A (Genistein) | Monitor Drug Delivery by Measuring Plasma Genistein by HPLC | Postmenopausal with ER- Cancer | 368.62 ng/ml | Standard Deviation 389.24 |
| Arm A (Genistein) | Monitor Drug Delivery by Measuring Plasma Genistein by HPLC | Postmenopausal with ER+ Cancer | 65.20 ng/ml | Standard Deviation 92.2 |
| Arm A (Genistein) | Monitor Drug Delivery by Measuring Plasma Genistein by HPLC | Postmenopausal Without Cancer | 190.42 ng/ml | Standard Deviation 226.17 |
| Arm A (Genistein) | Monitor Drug Delivery by Measuring Plasma Genistein by HPLC | Premenopausal with ER- Cancer | 472.09 ng/ml | Standard Deviation 350.16 |
| Arm A (Genistein) | Monitor Drug Delivery by Measuring Plasma Genistein by HPLC | Premenopausal with ER+ Cancer | 423.12 ng/ml | Standard Deviation 359 |
| Arm A (Genistein) | Monitor Drug Delivery by Measuring Plasma Genistein by HPLC | Premenopausal without cancer | 269.88 ng/ml | Standard Deviation 250.43 |
| Arm B (Placebo) | Monitor Drug Delivery by Measuring Plasma Genistein by HPLC | Premenopausal with ER+ Cancer | 3.80 ng/ml | Standard Deviation 4.4 |
| Arm B (Placebo) | Monitor Drug Delivery by Measuring Plasma Genistein by HPLC | Postmenopausal with ER- Cancer | 0 ng/ml | Standard Deviation 0 |
| Arm B (Placebo) | Monitor Drug Delivery by Measuring Plasma Genistein by HPLC | Premenopausal with ER- Cancer | 4.56 ng/ml | Standard Deviation 6.44 |
| Arm B (Placebo) | Monitor Drug Delivery by Measuring Plasma Genistein by HPLC | Postmenopausal with ER+ Cancer | 0 ng/ml | Standard Deviation 0 |
| Arm B (Placebo) | Monitor Drug Delivery by Measuring Plasma Genistein by HPLC | Premenopausal without cancer | 3.57 ng/ml | Standard Deviation 14.99 |
| Arm B (Placebo) | Monitor Drug Delivery by Measuring Plasma Genistein by HPLC | Postmenopausal Without Cancer | 0.65 ng/ml | Standard Deviation 2.52 |
Secondary
Plasma Concentration of Sex Hormone Binding Globulin (SHBG)
Time frame: 6 months - baseline
Population: Plasma concentration of SHBG was not available for 1 patient in Arm A. Analysis performed by menopause and cancer status.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Arm A (Genistein) | Plasma Concentration of Sex Hormone Binding Globulin (SHBG) | Premenopausal without cancer | -11.18 nmol/L | Standard Deviation 39.9 |
| Arm A (Genistein) | Plasma Concentration of Sex Hormone Binding Globulin (SHBG) | Postmenopausal Without Cancer | 3.94 nmol/L | Standard Deviation 26.42 |
| Arm A (Genistein) | Plasma Concentration of Sex Hormone Binding Globulin (SHBG) | Premenopausal with ER- Cancer | 15.61 nmol/L | Standard Deviation 14.79 |
| Arm A (Genistein) | Plasma Concentration of Sex Hormone Binding Globulin (SHBG) | Postmenopausal with ER- Cancer | 7.39 nmol/L | Standard Deviation 28.64 |
| Arm A (Genistein) | Plasma Concentration of Sex Hormone Binding Globulin (SHBG) | Postmenopausal with ER+ Cancer | -17.84 nmol/L | Standard Deviation 0.55 |
| Arm A (Genistein) | Plasma Concentration of Sex Hormone Binding Globulin (SHBG) | Premenopausal with ER+ Cancer | 1.99 nmol/L | Standard Deviation 15.26 |
| Arm B (Placebo) | Plasma Concentration of Sex Hormone Binding Globulin (SHBG) | Postmenopausal with ER+ Cancer | -8.12 nmol/L | Standard Deviation 13.4 |
| Arm B (Placebo) | Plasma Concentration of Sex Hormone Binding Globulin (SHBG) | Postmenopausal with ER- Cancer | 22.07 nmol/L | Standard Deviation 50.65 |
| Arm B (Placebo) | Plasma Concentration of Sex Hormone Binding Globulin (SHBG) | Postmenopausal Without Cancer | -20.49 nmol/L | Standard Deviation 50.03 |
| Arm B (Placebo) | Plasma Concentration of Sex Hormone Binding Globulin (SHBG) | Premenopausal with ER+ Cancer | -14.79 nmol/L | Standard Deviation 17.41 |
| Arm B (Placebo) | Plasma Concentration of Sex Hormone Binding Globulin (SHBG) | Premenopausal with ER- Cancer | -27.34 nmol/L | Standard Deviation 12.13 |
| Arm B (Placebo) | Plasma Concentration of Sex Hormone Binding Globulin (SHBG) | Premenopausal without cancer | 3.79 nmol/L | Standard Deviation 29.96 |