Breast Cancer
Conditions
Keywords
Green tea, Breast cancer, Prevention, COMT genotype, EGCG (Epigallocatechin gallate), Mammographic density, Reproductive hormones, IGF axis proteins, Oxidative stress
Brief summary
RATIONALE: Green tea extract contains ingredients (catechins) that may lower the risk of breast cancer. PURPOSE: This phase II trial is studying how well green tea extract works in preventing breast cancer compared to a placebo in postmenopausal women with high breast density. The investigators have hypothesized that green tea consumption reduces breast cancer risk, and this effect is seen primarily in women who have the low-activity COMT genotype. The investigators will test this by evaluating the effects of green tea extract on breast cancer biomarkers including mammographic density, plasma insulin-like growth factor 1 (IGF-1), IGF binding protein 3 (IGFBP-3), estrone, estradiol, androstenedione, sex hormone binding globulin (SHBG), urinary estrogen metabolites and plasma F2-isoprostanes.
Detailed description
OBJECTIVES: 1. Primary: 1.1 To determine the effects of green tea extract consumption (containing 800 mg EGCG per day) for 12 months on the following recognized biomarkers of breast cancer risk: 1. Mammographic density 2. Circulating concentrations of insulin-like growth factor 1 (IGF-1) and IGF binding protein 3 (IGFBP-3) 3. Circulating concentrations of reproductive hormones (estrone, estradiol, androstenedione) and sex hormone binding globulin (SHBG) 1.2 To determine the effects of COMT genotype on the green tea extract effects described above. 2. Secondary: 2.1 To determine the effects of green tea extract consumption (containing 800 mg EGCG per day) for 12 months on the following hypothesized biomarkers of breast cancer risk: 1. Urinary estrogen metabolites (estrone, estradiol, and their 2-hydroxy, 4-hydroxy, 2-methoxy, and 4-methoxy metabolites, estriol, and 16- hydroxyestrone) 2. Circulating concentrations of F-2 isoprostanes, a recognized biomarker of systemic oxidative stress 2.2 To determine the effects of COMT genotype on the green tea extract effects described above. 2.3 To determine the effects of COMT genotype on catechin metabolism and excretion, as measured by circulating and urinary concentrations.
Interventions
DRUGGreen tea extract supplement
Two green tea extract capsules twice daily after breakfast and dinner for one year
OTHERPlacebo
Two placebo capsules twice daily after breakfast and dinner for one year
Sponsors
National Cancer Institute (NCI)
University of Minnesota
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
FEMALE
Age
50 Years to 70 Years
Healthy volunteers
Yes
Inclusion criteria
* Signed informed consent * Healthy postmenopausal women aged 50-70 years * Heterogeneously dense (51-75% glandular) or extremely dense (\>75%glandular) breasts * Willing to avoid consumption of green tea for 1 year
Exclusion criteria
* Positive serological markers of hepatitis B or hepatitis C infections * Elevated levels of liver enzymes * Recent (within 6 mo) or current hormone or hormone modification therapy, including systemic hormone replacement therapy, SERMS and aromatase inhibitors * Current smoker of cigarettes or other tobacco products * BMI \<19 or \>40 kg/m2 * Weight change \> 10 lbs during the previous year * History of breast cancer or proliferative breast disease * Regular consumption of \> 7 alcoholic drinks/wk * Regular consumption of green tea (\>1 cup/wk) * Recent (within 6 mo) or current use of chemopreventive agents such as tamoxifen, raloxifene or aromatase inhibitors * Participation in any weight loss or weight gain studies * Currently taking Methotrexate or Enbrel * History of ovarian cancer * Any form of cancer in the last 5 years * Presence of implants
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mammographic Density | Baseline and month 12 | Percent mammographic density was measured on digital images using a computer-assisted and quantitative method. |
| Circulating Concentrations of Reproductive Hormones Including Estrone, Estradiol, Androstenedione, Testosterone, and Sex Hormone Binding Globulin (SHBG) | Baseline and month 12 | Circulating levels of reproductive hormones including estrone, estradiol, androstenedione, testosterone and SHBG were measured in fasting blood samples by liquid chromatography/tandem mass spectrometry method. |
| Circulating Concentrations of IGF Axis Proteins Including IGF-1 and IGFBP-3 | Baseline and month 12 | Circulating levels of IGF-1 and IGFBP-3 were measured in fasting blood samples by ELISA method. |
Countries
United States
Participant flow
Recruitment details
August 2009 through April 2013
Pre-assignment details
Prior to randomization, participants went through a screening clinic visit in which anthropometric characteristics and blood pressure were measured. In addition, blood was drawn to assess catechol-O-methyltransferase (COMT) genotype, hepatic function, and serological markers of hepatitis B and C virus.
Participants by arm
| Arm | Count |
|---|---|
| Green Tea Extract Green tea extract supplement: Two green tea extract capsules twice daily after breakfast and dinner for one year | 538 |
| Sugar Pill Placebo: Two placebo capsules twice daily after breakfast and dinner for one year | 537 |
| Total | 1,075 |
Baseline characteristics
| Characteristic | Total | Green Tea Extract | Sugar Pill |
|---|---|---|---|
| Age, Continuous | 59.8 years STANDARD_DEVIATION 5.02 | 59.9 years STANDARD_DEVIATION 5 | 59.6 years STANDARD_DEVIATION 5.1 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 11 Participants | 5 Participants | 6 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 1026 Participants | 516 Participants | 510 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 38 Participants | 17 Participants | 21 Participants |
| Height | 163.9 cm STANDARD_DEVIATION 6.2 | 163.5 cm STANDARD_DEVIATION 6.3 | 164.3 cm STANDARD_DEVIATION 6.2 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 10 Participants | 3 Participants | 7 Participants |
| Race (NIH/OMB) Black or African American | 11 Participants | 4 Participants | 7 Participants |
| Race (NIH/OMB) More than one race | 6 Participants | 4 Participants | 2 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 28 Participants | 12 Participants | 16 Participants |
| Race (NIH/OMB) White | 1020 Participants | 515 Participants | 505 Participants |
| Region of Enrollment United States | 1075 participants | 538 participants | 537 participants |
| Sex: Female, Male Female | 1075 Participants | 538 Participants | 537 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
| Waist-to-hip ratio | 0.83 Ratio STANDARD_DEVIATION 0.07 | 0.84 Ratio STANDARD_DEVIATION 0.1 | 0.83 Ratio STANDARD_DEVIATION 0.1 |
| Weight | 67.4 kg STANDARD_DEVIATION 10.5 | 67.4 kg STANDARD_DEVIATION 10.6 | 67.9 kg STANDARD_DEVIATION 10.5 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 407 / 538 | 391 / 537 |
| serious Total, serious adverse events | 12 / 538 | 8 / 537 |
Outcome results
Primary
Circulating Concentrations of IGF Axis Proteins Including IGF-1 and IGFBP-3
Circulating levels of IGF-1 and IGFBP-3 were measured in fasting blood samples by ELISA method.
Time frame: Baseline and month 12
Population: Circulating concentrations of IGF axis proteins including insulin-like growth factor (IGF-1) and IGF binding protein 3 (IGFBP-3) at baseline and month 12
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Green Tea Extract | Circulating Concentrations of IGF Axis Proteins Including IGF-1 and IGFBP-3 | Circulating IGF-1 at baseline | 87.5 ng/ml |
| Green Tea Extract | Circulating Concentrations of IGF Axis Proteins Including IGF-1 and IGFBP-3 | Circulating IGF-1 at month 12 | 83.7 ng/ml |
| Green Tea Extract | Circulating Concentrations of IGF Axis Proteins Including IGF-1 and IGFBP-3 | Circulating IGFBP-3 at baseline | 2048.0 ng/ml |
| Green Tea Extract | Circulating Concentrations of IGF Axis Proteins Including IGF-1 and IGFBP-3 | Circulating IGFBP-3 at month 12 | 2048.1 ng/ml |
| Sugar Pill | Circulating Concentrations of IGF Axis Proteins Including IGF-1 and IGFBP-3 | Circulating IGFBP-3 at month 12 | 2040.7 ng/ml |
| Sugar Pill | Circulating Concentrations of IGF Axis Proteins Including IGF-1 and IGFBP-3 | Circulating IGF-1 at baseline | 88.3 ng/ml |
| Sugar Pill | Circulating Concentrations of IGF Axis Proteins Including IGF-1 and IGFBP-3 | Circulating IGFBP-3 at baseline | 2047.6 ng/ml |
| Sugar Pill | Circulating Concentrations of IGF Axis Proteins Including IGF-1 and IGFBP-3 | Circulating IGF-1 at month 12 | 83.1 ng/ml |
Primary
Circulating Concentrations of Reproductive Hormones Including Estrone, Estradiol, Androstenedione, Testosterone, and Sex Hormone Binding Globulin (SHBG)
Circulating levels of reproductive hormones including estrone, estradiol, androstenedione, testosterone and SHBG were measured in fasting blood samples by liquid chromatography/tandem mass spectrometry method.
Time frame: Baseline and month 12
Population: Circulating concentrations of reproductive hormones including estrone, estradiol, androstenedione, testosterone, sex hormone binding globulin (SHBG) at baseline and month 12
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Green Tea Extract | Circulating Concentrations of Reproductive Hormones Including Estrone, Estradiol, Androstenedione, Testosterone, and Sex Hormone Binding Globulin (SHBG) | Circulating estrone at baseline | 22.8 pg/ml |
| Green Tea Extract | Circulating Concentrations of Reproductive Hormones Including Estrone, Estradiol, Androstenedione, Testosterone, and Sex Hormone Binding Globulin (SHBG) | Circulating estrone at month 12 | 22.5 pg/ml |
| Green Tea Extract | Circulating Concentrations of Reproductive Hormones Including Estrone, Estradiol, Androstenedione, Testosterone, and Sex Hormone Binding Globulin (SHBG) | Circulating estradiol at baseline | 3.4 pg/ml |
| Green Tea Extract | Circulating Concentrations of Reproductive Hormones Including Estrone, Estradiol, Androstenedione, Testosterone, and Sex Hormone Binding Globulin (SHBG) | Circulating estradiol at month 12 | 3.7 pg/ml |
| Green Tea Extract | Circulating Concentrations of Reproductive Hormones Including Estrone, Estradiol, Androstenedione, Testosterone, and Sex Hormone Binding Globulin (SHBG) | Circulating androstenedione at baseline | 479.8 pg/ml |
| Green Tea Extract | Circulating Concentrations of Reproductive Hormones Including Estrone, Estradiol, Androstenedione, Testosterone, and Sex Hormone Binding Globulin (SHBG) | Circulating androstenedione at month 12 | 468.8 pg/ml |
| Green Tea Extract | Circulating Concentrations of Reproductive Hormones Including Estrone, Estradiol, Androstenedione, Testosterone, and Sex Hormone Binding Globulin (SHBG) | Circulating testosterone at baseline | 151.0 pg/ml |
| Green Tea Extract | Circulating Concentrations of Reproductive Hormones Including Estrone, Estradiol, Androstenedione, Testosterone, and Sex Hormone Binding Globulin (SHBG) | Circulating testosterone at month 12 | 158.1 pg/ml |
| Green Tea Extract | Circulating Concentrations of Reproductive Hormones Including Estrone, Estradiol, Androstenedione, Testosterone, and Sex Hormone Binding Globulin (SHBG) | Circulating SHBG at baseline | 68.1 pg/ml |
| Green Tea Extract | Circulating Concentrations of Reproductive Hormones Including Estrone, Estradiol, Androstenedione, Testosterone, and Sex Hormone Binding Globulin (SHBG) | Circulating SHBG at month 12 | 68.7 pg/ml |
| Sugar Pill | Circulating Concentrations of Reproductive Hormones Including Estrone, Estradiol, Androstenedione, Testosterone, and Sex Hormone Binding Globulin (SHBG) | Circulating testosterone at month 12 | 155.1 pg/ml |
| Sugar Pill | Circulating Concentrations of Reproductive Hormones Including Estrone, Estradiol, Androstenedione, Testosterone, and Sex Hormone Binding Globulin (SHBG) | Circulating estrone at baseline | 23.6 pg/ml |
| Sugar Pill | Circulating Concentrations of Reproductive Hormones Including Estrone, Estradiol, Androstenedione, Testosterone, and Sex Hormone Binding Globulin (SHBG) | Circulating androstenedione at month 12 | 479.5 pg/ml |
| Sugar Pill | Circulating Concentrations of Reproductive Hormones Including Estrone, Estradiol, Androstenedione, Testosterone, and Sex Hormone Binding Globulin (SHBG) | Circulating estrone at month 12 | 22.4 pg/ml |
| Sugar Pill | Circulating Concentrations of Reproductive Hormones Including Estrone, Estradiol, Androstenedione, Testosterone, and Sex Hormone Binding Globulin (SHBG) | Circulating SHBG at month 12 | 68.7 pg/ml |
| Sugar Pill | Circulating Concentrations of Reproductive Hormones Including Estrone, Estradiol, Androstenedione, Testosterone, and Sex Hormone Binding Globulin (SHBG) | Circulating estradiol at baseline | 3.7 pg/ml |
| Sugar Pill | Circulating Concentrations of Reproductive Hormones Including Estrone, Estradiol, Androstenedione, Testosterone, and Sex Hormone Binding Globulin (SHBG) | Circulating testosterone at baseline | 161.6 pg/ml |
| Sugar Pill | Circulating Concentrations of Reproductive Hormones Including Estrone, Estradiol, Androstenedione, Testosterone, and Sex Hormone Binding Globulin (SHBG) | Circulating estradiol at month 12 | 3.1 pg/ml |
| Sugar Pill | Circulating Concentrations of Reproductive Hormones Including Estrone, Estradiol, Androstenedione, Testosterone, and Sex Hormone Binding Globulin (SHBG) | Circulating SHBG at baseline | 69.1 pg/ml |
| Sugar Pill | Circulating Concentrations of Reproductive Hormones Including Estrone, Estradiol, Androstenedione, Testosterone, and Sex Hormone Binding Globulin (SHBG) | Circulating androstenedione at baseline | 507.2 pg/ml |
Primary
Mammographic Density
Percent mammographic density was measured on digital images using a computer-assisted and quantitative method.
Time frame: Baseline and month 12
Population: Mammographic density at baseline and month 12
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Green Tea Extract | Mammographic Density | Percent mammographic density at baseline | 22.71 Percent |
| Green Tea Extract | Mammographic Density | Percent mammographic density at month 12 | 22.09 Percent |
| Sugar Pill | Mammographic Density | Percent mammographic density at baseline | 21.84 Percent |
| Sugar Pill | Mammographic Density | Percent mammographic density at month 12 | 21.13 Percent |