Clinical trial NCT00917735: Green Tea and Reduction of Breast Cancer Risk
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Breast Cancer
Keywords: Green tea
Breast cancer
Prevention
COMT genotype
EGCG (Epigallocatechin gallate)
Mammographic density
Reproductive hormones
IGF axis proteins
Oxidative stress
Lead sponsor: University of Minnesota
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2009-06-10
Enrollment: 1075
Sex: FEMALE
Minimum age (years): 50
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

Eligibility criteria: 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

Primary outcomes:
measure: Mammographic Density
timeFrame: Baseline and month 12
measure: Circulating Concentrations of Reproductive Hormones Including Estrone, Estradiol, Androstenedione, Testosterone, and Sex Hormone Binding Globulin (SHBG)
timeFrame: Baseline and month 12
measure: Circulating Concentrations of IGF Axis Proteins Including IGF-1 and IGFBP-3
timeFrame: Baseline and month 12
Secondary outcomes:
Other outcomes:
Locations:
city: Edina
country: United States
facility: Fairview Southdale Breast Center
state: Minnesota
city: Maple Grove
country: United States
facility: Fairview Maple Grove Breast Center
state: Minnesota
city: Minneapolis
country: United States
facility: University of Minnesota Medical Center (UMMC) Breast Clinic
state: Minnesota
city: St. Louis Park
country: United States
facility: Park Nicollet Institute
state: Minnesota
city: St. Paul
country: United States
facility: Food Science and Nutrition, University of Minnesota
state: Minnesota
Study officials:
affiliation: University of Minnesota
name: Mindy S Kurzer, Ph.D
role: PRINCIPAL_INVESTIGATOR
References:
citation: Samavat H, Wu AH, Ursin G, Torkelson CJ, Wang R, Yu MC, Yee D, Kurzer MS, Yuan JM. Green Tea Catechin Extract Supplementation Does Not Influence Circulating Sex Hormones and Insulin-Like Growth Factor Axis Proteins in a Randomized Controlled Trial of Postmenopausal Women at High Risk of Breast Cancer. J Nutr. 2019 Apr 1;149(4):619-627. doi: 10.1093/jn/nxy316.
citation: Arikawa AY, Samavat H, Gross M, Kurzer MS. Plasma F2-isoprostanes Are Positively Associated with Glycemic Load, but Inversely Associated with Dietary Polyunsaturated Fatty Acids and Insoluble Fiber in Postmenopausal Women. J Nutr. 2017 Sep;147(9):1693-1699. doi: 10.3945/jn.117.254631. Epub 2017 Jul 26.
citation: Samavat H, Newman AR, Wang R, Yuan JM, Wu AH, Kurzer MS. Effects of green tea catechin extract on serum lipids in postmenopausal women: a randomized, placebo-controlled clinical trial. Am J Clin Nutr. 2016 Dec;104(6):1671-1682. doi: 10.3945/ajcn.116.137075. Epub 2016 Nov 2.
citation: Dostal AM, Arikawa A, Espejo L, Kurzer MS. Long-Term Supplementation of Green Tea Extract Does Not Modify Adiposity or Bone Mineral Density in a Randomized Trial of Overweight and Obese Postmenopausal Women. J Nutr. 2016 Feb;146(2):256-64. doi: 10.3945/jn.115.219238. Epub 2015 Dec 23.
citation: Dostal AM, Samavat H, Espejo L, Arikawa AY, Stendell-Hollis NR, Kurzer MS. Green Tea Extract and Catechol-O-Methyltransferase Genotype Modify Fasting Serum Insulin and Plasma Adiponectin Concentrations in a Randomized Controlled Trial of Overweight and Obese Postmenopausal Women. J Nutr. 2016 Jan;146(1):38-45. doi: 10.3945/jn.115.222414. Epub 2015 Nov 18.