Green Tea and Reduction of Breast Cancer Risk

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

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.

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.

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