Green Tea and Reduction of Breast Cancer Risk

Phase 2

Completed

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.

Recruitment & Eligibility

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

Arm && Interventions

Group	Intervention	Description
Green tea extract	Green tea extract supplement	Green tea extract capsules containing 80.7 % total catechins (51.7 % EGCG)
Sugar pill	Placebo	Placebo capsules containing 50% maltodextrin, 49.5 % cellulose, and 0.5 % magnesium stearate

Primary Outcome Measures

Name	Time	Method
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.

Secondary Outcome Measures

Name	Time	Method

Locations (5): University of Minnesota Medical Center (UMMC) Breast Clinic
🇺🇸
Minneapolis, Minnesota, United States
Park Nicollet Institute
🇺🇸
St. Louis Park, Minnesota, United States
Food Science and Nutrition, University of Minnesota
🇺🇸
St. Paul, Minnesota, United States
Fairview Southdale Breast Center
🇺🇸
Edina, Minnesota, United States
Fairview Maple Grove Breast Center
🇺🇸
Maple Grove, Minnesota, United States