Background: Green tea intake may be associated with reduced risk of several cancers including breast cancer. One of the proposed mechanisms by which green tea may modify breast cancer risk is through effects on estrogen metabolism. Genetic variation in catechol-O-methyltransferase (COMT), an enzyme involved in the metabolism of both estrogens and tea catechins, may also have a role. Few studies have examined the effects of green tea intake on circulating and urinary estrogens and estrogen metabolites, and even less is known about the potential modifying influence of polymorphisms in the COMT gene.

Objectives: To investigate the effects of daily intake of a highly concentrated green tea extract (GTE) for one year on circulating and urinary estrogens and their metabolites in postmenopausal women with different COMT genotypes.

Methods: The Minnesota Green Tea Trial (MGTT), a randomized, double-blind, placebo-controlled, phase II clinical trial, enrolled 1075 healthy postmenopausal women with heterogeneously or extremely dense breast tissue (age = 59.78 ± 5.02 years; body mass index = 25.70 ± 8.21 kg/m2). Participants were 93% non-Hispanic white and non-current hormone users. Half of the participants (n = 538) were randomly assigned to the GTE group and were given 4 capsules a day, each containing 200 mg epigallocatechin gallate (EGCG) and the others (n = 537) to the placebo group. Twenty-four hour urine samples were collected at month 0 and at the end of the study, and fasting blood samples were drawn at months 0, 6 and 12. Circulating and urinary estrogens, as well as urinary estrogen metabolites were quantified by liquid chromatography-tandem mass spectrometry.

Results: GTE supplementation was associated with reduced urinary estriol (-10.7%, P = 0.08) and 2-methoxy estrone (-12.2%, P = 0.014) compared with baseline, and these changes were significantly greater than the corresponding changes in the placebo group (P = 0.003, and P = 0.02, respectively). GTE supplementation had no significant effects

on serum or urinary estrone and estradiol. Among women with the low activity COMT genotype, GTE supplementation reduced urinary estrone (-5.3%) compared with women with high activity COMT (+2.1%) (between groups comparison P = 0.049). Statistical analyses are ongoing to examine the potential modifying effects of COMT genotype on other urinary estrogen metabolites.

Conclusion: Daily intake of high-dose green tea extract for 12 months exerts significant effects on urinary excretion of estrogen metabolites, and these effects may be modified by

COMT polymorphisms. The potential beneficial effects of green tea extract on estrogen metabolism support the further development of green tea as a potential chemopreventive agents for estrogen-related disease prevention.

Funding source: NIH/NCI (R01 CA127236).

Citation Format: Hamed Samavat, Renwei Wang, Anna Wu, Jian-Min Yuan, Mindy Kurzer. Green tea extract supplementation, estrogen metabolism and breast cancer risk in postmenopausal women at high risk of breast cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr CT111. doi:10.1158/1538-7445.AM2015-CT111