Green Tea and Reduction of Breast Cancer Risk

Study Overview
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Brief Summary
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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
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OBJECTIVES: 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: Mammographic density Circulating concentrations of insulin-like growth factor 1 (IGF-1) and IGF binding protein 3 (IGFBP-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. 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: Urinary estrogen metabolites (estrone, estradiol, and their 2-hydroxy, 4-hydroxy, 2-methoxy, and 4-methoxy metabolites, estriol, and 16- hydroxyestrone) 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.

Official Title
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Phase II, Randomized,Double-blind, Placebo-controlled, Study of the Efficacy of Green Tea Extract on Biomarkers of Breast Cancer Risk in High Risk Women With Differing Catechol-O-methyl Transferase (COMT) Genotypes

Conditions
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Breast Cancer

Intervention / Treatment
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* Drug: Green tea extract supplement
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 50 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Green tea extract<br>Green tea extract capsules containing 80.7 % total catechins (51.7 % EGCG) | Drug: Green tea extract supplement<br>* Two green tea extract capsules twice daily after breakfast and dinner for one year<br>* Other names: Green tea extract: Corban green tea blend (GTB-3D);|
| Placebo Comparator: Sugar pill<br>Placebo capsules containing 50% maltodextrin, 49.5 % cellulose, and 0.5 % magnesium stearate | Other: Placebo<br>* Two placebo capsules twice daily after breakfast and dinner for one year<br>* Other names: Sugar Pill;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mammographic Density | Percent mammographic density was measured on digital images using a computer-assisted and quantitative method. | Baseline and month 12 | 
| 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. | Baseline and month 12 | 
| 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. | Baseline and month 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Green tea, Breast cancer, Prevention, COMT genotype, EGCG (Epigallocatechin gallate), Mammographic density, Reproductive hormones, IGF axis proteins, Oxidative stress