Abstract PR-05: Effects of presurgical administration of tea polyphenols in women with operable breast cancer
Authors: Campbell Julie L. , Cardelli James , McLarty Jerry , Hershman Dawn , Taback Bret , Refice Susan , Wang Stephanie , Bigelow Rebecca , Crew Katherine 
Published: January 2011

Abstract
Background: Various epidemiologic studies have demonstrated an inverse association between green tea consumption and breast cancer risk. The primary polyphenol of green tea, epigallocatechin gallate (EGCG), is a potent antioxidant that acts on multiple stages of carcinogenesis, including proliferation and angiogenesis. The hepatocyte growth factor (HGF)/c-Met pathway is deregulated in breast cancer, with high levels of serum HGF and its tissue receptor c-Met being associated with a poorer prognosis in the clinical setting. Polyphenols have been shown to modulate these pathways in human breast cancer cell lines and mouse xenograft models, however, studies in humans are notably lacking. The purpose of this study was to determine the effects of short-term presurgical administration of an oral green tea extract, Polyphenon E (Poly E), on serum and tissue-based biomarkers in patients with operable breast cancer.
Methods: This is a phase II single-arm open-label trial of oral Poly E 800 mg daily for 2-4 weeks in women with histologically confirmed breast cancer on core biopsy who were scheduled for surgical resection. Poly E is a purified tea fraction containing 800 mg of EGCG and lesser amounts of other green tea catechins. Safety was assessed by monitoring clinical and laboratory parameters at baseline and the end of treatment. Serum was collected at baseline and the day prior to surgery and analyzed for HGF and VEGF levels by ELISA. All pretreatment and posttreatment samples were run in the same batch and analyzed in a blinded fashion. Formalin-fixed paraffin-embedded tumor tissue from the diagnostic core biopsy (pretreatment) and surgical specimen (posttreatment) were analyzed for expression of the Ki-67 proliferation index by immunohistochemistry. Pre- and posttreatment values for each biomarker were compared using paired t-test or nonparametric analog. All statistical analyses were two-sided and performed using SAS version 9.1.
Results: From February 2008 to September 2009, 25 women were enrolled of which 21 are evaluable. Median age: 49 (33-71); White/Hispanic/Black: 7/13/1; Stage 0/I/II/III: 3/11/4/2; Tumor hormone receptor +/−: 18/3. The study drug was well tolerated with no grade 2 or higher toxicities. Poly E administration was associated with a trend toward decreasing serum HGF levels (mean absolute change of −240 pg/ml, mean % change of −13.5%, p=0.077). No significant change in serum VEGF levels was observed. Tissue-based biomarker analyses are currently ongoing.
Conclusions: Our results show a nonsignificant trend towards a decrease in serum HGF levels in women with newly diagnosed early stage breast cancer after short-term administration of Poly E. The treatment was well tolerated, with no significant elevation of liver or pancreatic enzymes. This presurgical study design is a useful and feasible model for testing the biologic effects of potential agents for breast cancer treatment and prevention.
Citation Information: Cancer Prev Res 2010;3(12 Suppl):PR-05.