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Epigallocatechin gallate

Epigallocatechin

Catechin

Epicatechin

Catechol

Green tea extract capsules containing 80.7 % total catechins (51.7 % EGCG)

Placebo capsules containing 50% maltodextrin, 49.5 % cellulose, and 0.5 % magnesium stearate

Two green tea extract capsules twice daily after breakfast and dinner for one year

Green tea extract supplement

Two placebo capsules twice daily after breakfast and dinner for one year

Placebo

Mindy S Kurzer, Ph.D

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.

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

Percent mammographic density was measured on digital images using a computer-assisted and quantitative method.

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 levels of IGF-1 and IGFBP-3 were measured in fasting blood samples by ELISA method.

National Cancer Institute (NCI)

University of Minnesota

Adverse event information was coded and graded using the National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE), version 4.03.

Green tea extract (GTE) supplement: Two green tea extract capsules twice daily after breakfast and dinner for one year. GTE was a decaffeinated green tea extract, and each capsule contained a total of 328.8 ± 28.9 mg catechins including 210.7 ± 11.0 mg of EGCG.

Green Tea Extract

Placebo: Two placebo capsules twice daily after breakfast and dinner for one year. Placebo capsules contained maltodextrin, cellulose, and magnesium stearate.

Sugar Pill

Green tea extract supplement: Two green tea extract capsules twice daily after breakfast and dinner for one year

Placebo: Two placebo capsules twice daily after breakfast and dinner for one year

Total

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Region of Enrollment

Height

Weight

Waist-to-hip ratio

We had limited success in recruiting minority populations.

Dr. Mindy Kurzer

Percent mammographic density at baseline

Percent mammographic density at month 12

Mammographic density at baseline and month 12

Mammographic Density

Circulating estrone at baseline

Circulating estrone at month 12

Circulating estradiol at baseline

Circulating estradiol at month 12

Circulating androstenedione at baseline

Circulating androstenedione at month 12

Circulating testosterone at baseline

Circulating testosterone at month 12

Circulating SHBG at baseline

Circulating SHBG at month 12

Circulating concentrations of reproductive hormones including estrone, estradiol, androstenedione, testosterone, sex hormone binding globulin (SHBG) at baseline and month 12

Circulating Concentrations of Reproductive Hormones Including Estrone, Estradiol, Androstenedione, Testosterone, and Sex Hormone Binding Globulin (SHBG)

Circulating IGF-1 at baseline

Circulating IGF-1 at month 12

Circulating IGFBP-3 at baseline

Circulating IGFBP-3 at month 12

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

Circulating Concentrations of IGF Axis Proteins Including IGF-1 and IGFBP-3

Green tea extract (GTE) supplement: Two green tea extract capsules twice daily after breakfast and dinner for one year. GTE was a decaffeinated green tea extract, and each capsule contained a total of 328.8 ± 28.9 mg catechins including 210.7 ± 11.0 mg of epigallocatechin gallate (EGCG).

Overall Study

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Gland and Hormone Related Diseases

Premature Birth

Infertility

Infertility, Female

Primary Ovarian Insufficiency

Menopause, Premature

Menopause

Clarisa R Gracia, MD, MSCE

Postmenarchal female cancer patients scheduled to undergo cancer therapy may enroll in this study to assess changes in existing and novel surrogate measures of fertility potential before, during and after chemotherapy. Measures of fertility potential to be tested include ultrasound imaging for antral follicle counts and ovarian volumes, endocrine evaluation, and assessment of oxidative stress.

Eligible women are asked to complete a structured interview, questionnaires, a monthly menstrual diary, a brief physical examination, a blood test, and an abdominal or pelvic ultrasound at baseline and at 3 month intervals following start of chemotherapy through 6 months post end of treatment.

Within subject changes in continuous variables (hormones, urinary isoprostane levels, ovarian volume, AFC) will be compared using paired t-tests (nonparametric tests as appropriate). Non-Gaussian-distributed variables will be logarithmically transformed prior to analysis. In general, changes from baseline to every 3 month assessment will be compared individually as well as changes from baseline to post treatment. In addition, regression models for repeated measures will be used to describe the pattern of change in these outcomes over time. Additional models will be constructed to adjust for potential confounding variables including age, chemotherapy type, dose and duration of treatment, radiation treatment, gonadotropin releasing hormone agonist use, and hormone use. Finally, regression models will be used to evaluate the association between changes in urinary isoprostane levels over the study with changes in endocrine measures.

The Longitudinal Ovarian Reserve Study

The Effects of Cancer Treatment on Ovarian Function: A Longitudinal Study by the Oncofertility Consortium

20 mls blood will be obtained at stated timepoints for determining levels of Follicle Stimulating Hormone (FSH), Luteinizing Hormone (LH), Estradiol (E2), Inhibin B, and Anti-mullerian Hormone (AMH). In menstruating girls and young women hormone measures will be obtained during the early follicular phase of the menstrual cycle (days 1-4). In women with irregular cycles the testing will be done spontaneously without regard for the bleeding pattern.

Ovaries will be measured in three dimensions. Uterine size and endometrial thickness will also be performed. The transvaginal approach is preferred, but transabdominal ultrasound will be performed in girls who do not feel comfortable with the transvaginal procedure.

Antral Follicle Counts by size (2-5 mm, 6-9 mm, and \>9 mm in diameter) will be determined.

24 hour urine collection will be analyzed to assess urinary 8,12-iso-iPF2alpha-VI isoprostane levels.

Subjects are asked to document menstrual bleeding in a diary, noting duration of each menstrual period in days, bleeding intensity (spotting, light, moderate, heavy, flooding, none), and intervals between periods.

The validated "Menopausal Symptom List" (MSL) will be used at each study visit to assess the presence or absence of menopausal symptoms during the past month, the frequency and severity of each symptom. Symptoms captured include: hot flashes, vaginal dryness, concentration/memory problems, irritability, mood swings, feeling sad, feeling anxious, trouble sleeping, aches, joint pain, headaches.

One of two well validated and widely used questionnaires will assess Quality of Life measures: For adolescents 20 years of age or younger, the Minneapolis-Manchester Quality of Life (MMQL) - Adolescent Form will be administered. This questionnaire assesses demographics, physical functioning, cognitive functioning, psychological functioning, body image, social functioning, outlook on life, and intimate relations in cancer survivors. The MMQL is a 46 item validated, standardized self-report instrument designed to assess health related quality of life in adolescent survivors of cancer.

Subjects over 20 years of age will be asked to complete a self report quality of life questionnaire entitled Assessing Quality of Life in Adult Cancer Survivors (QLACS). This questionnaire has been proven to be valid and reliable for comparing quality of life in adult cancer survivors and non-cancer patients.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Green Tea and Reduction of Breast Cancer Risk	NCT00917735	Breast Cancer	Green tea extra... Placebo	50 Years - 70 Years	University of Minnesota
Green Tea and Reduction of Breast Cancer Risk	NCT00917735	Breast Cancer	Green tea extra... Placebo	50 Years - 70 Years	University of Minnesota
The Longitudinal Ovarian Reserve Study	NCT02395341	Effects of Chem...		15 Years - 45 Years	University of Pennsylvania

Spots Global Cancer Trial Database for reproductive hormones