Abstract B65: Biomarker effects of an oral green tea extract, Polyphenon E, in women with a history of hormone receptor-negative breast cancer

Background: Observational studies have correlated green tea intake with reduced breast cancer risk. In preclinical studies, the main polyphenol of green tea, epigallocatechin-3-gallate (EGCG), inhibits growth factors, such as vascular endothelial growth factor (VEGF) and hepatocyte growth factor (HGF), which influence tumor cell growth, migration, and invasion. We conducted an ancillary study using archived serum and urine from a completed phase IB randomized, placebo-controlled dose escalation trial of an oral green tea extract, Polyphenon E (Poly E), in women with hormone receptor (HR)-negative breast cancer. The objective was to understand the effects of Poly E on potential biomarkers of breast cancer risk. Methods: Forty women with stage I-III HR-negative breast cancer who completed adjuvant treatment were randomized using an adaptive trial design to Poly E 400 mg (n = 16), 600 mg (n = 11), 800 mg (n = 3) twice daily or matching placebo (n = 10) for 6 months. Blood and urine collection occurred at baseline, 2, 4, and 6 months. Biologic endpoints included oxidative damage (urine 8-oxoG and isoprostane, plasma carbonyls), inflammatory (serum C-reactive protein [CRP], urine prostaglandin E2 metabolite [PGE-M]), growth factor (serum VEGF, HGF), and lipid (total cholesterol, triglycerides) biomarkers, as well as total urinary tea polyphenols. Results: From July 2007 to Sept 2009, 40 women were enrolled from 4 sites. During the intervention, 5 women developed a dose-limiting toxicity which required stopping study drug, 4 were lost to follow-up, and complete biomarker data was available for 34 participants (26 Poly E, 8 placebo). Concentration of total urinary tea polyphenol metabolites increased from baseline by an average of 10-fold in the Poly E group (all dose levels combined) compared to placebo (p = 0.001). Within the Poly E group, the mean decrease from baseline in serum VEGF was statistically significant at months 2 (11.5%, p = 0.02) and 4 (13.9%, p = 0.04). However, these changes were not significant when compared to placebo. At 2 months, mean serum HGF levels decreased by 12.6% for Poly E compared to a 6.3% increase for placebo (p = 0.04). This trend persisted at 4 and 6 months, but was no longer statistically significant. With Poly E treatment, there was a non-significant trend toward a decrease from baseline in serum cholesterol at 2, 4, and 6 months. No significant differences were observed in the biomarkers of oxidative damage (urine 8-oxoG and isoprostane, plasma carbonyls) or inflammation (serum CRP, urine PGE-M) after treatment with Poly E compared to placebo. Discussion: We demonstrated a significant reduction in serum HGF and a favorable decline in serum VEGF and total cholesterol during a 6-month intervention of Poly E in women with breast cancer. Given the small sample size and lack of adjustment for multiple comparisons, these results need to be confirmed in a larger study. Nevertheless, these findings are consistent with published results from short-term intervention trials of Poly E. This suggests potential mechanisms of action of green tea in angiogenesis, growth factor signaling, and metabolic pathways. Citation Format: Katherine D. Crew, Kimberly A. Ho, Powel Brown, Heather Greenlee, Therese B. Bevers, Banu Arun, Clifford Hudis, Heather L. McArthur, Jenny Chang, Mothaffar Rimawi, Lana Vornik, Terri L. Cornelison, James Cardelli, Regina M. Santella, Antai Wang, Scott M. Lippman, Dawn L. Hershman. Biomarker effects of an oral green tea extract, Polyphenon E, in women with a history of hormone receptor-negative breast cancer. [abstract]. In: Proceedings of the Eleventh Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2012 Oct 16-19; Anaheim, CA. Philadelphia (PA): AACR; Cancer Prev Res 2012;5(11 Suppl):Abstract nr B65.