Evaluating Effects of an Oral Green Tea Extract, Polyphenon E, on Tissue Biomarkers, Using Reverse Phase Protein Array in Women with Operable Breast Cancer
Journal: International Journal of Food Science, Nutrition and Dietetics (IJFS) (Vol.04, No. 02)Publication Date: 2015-03-19
Authors : Ho KA; Cardelli JA; McLarty J; Hershman DL; Maurer M; Kalinsky K; Hibshoosh H; Su T; Refice SF; Crew KD;
Page : 190-196
Keywords : Biomarkers; Breast Cancer; Chemoprevention; Green Tea; Proteomics.;
Abstract
Experimental data support potential anti-tumor effects of green tea in breast cancer, yet limited data exists in human intervention trials. We conducted a phase 0 single-arm trial in women with newly diagnosed operable breast cancer given an oral green tea extract, Polyphenon E (Poly E), 800mg daily for at least 2 weeks prior to surgical resection. Among Poly E-treated cases and matched historical controls, changes in tumor protein expression from the diagnostic core biopsy (pretreatment) and surgical resection (post-treatment) were analyzed by immunohistochemistry (IHC) for Ki67 proliferation index, estrogen receptor (ER), progesterone receptor (PR), HER2, and reverse phase protein array (RPPA). From February 2008 to September 2009, 27 women were enrolled and 21 were evaluable. Median duration on Poly E was 20days (range, 13-36 days). We demonstrated significant correlations between IHC and RPPA for Ki67 (p<0.0001), ER (p=0.0017), and PR (p=0.0014). Poly E treatment did not cause a significant decrease in Ki67 compared to untreated controls (mean absolute change, -0.5% vs. +2.6%; p=0.83). The Poly E-treated group showed a significant change from baseline in PI3K/AKT pathway proteins, HSP90 clients, and Src/STAT activity. Compared to untreated controls, the Poly E group had significant down-regulation of PRAS40-pT246, MIG-6, and Src-pY416 and up-regulation of Notch1. Short-term administration of Poly E did not significantly decrease proliferation in breast tumor tissue; however, our RPPA data suggests that Poly E may act on alternative pathways. This is the first human intervention trial to demonstrate the biologic effects of Poly E on growth factor signaling in breast cancer.
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