A Study of the Effect of Polyphenon E (Green Tea Extract) on Breast Cancer Progression

Phase II Clinical Trial to Determine if Polyphenon E Inhibits c-Met Signaling and Activation of Pathways Contributing to Breast Cancer Progression

To see if an extract of green tea can affect certain markers of breast cancer and breast cancer progression in women with a recent biopsy positive for cancer and who are scheduled for surgery.

To evaluate the short-term effects of a daily dose of Polyphenon E administered during the interval between breast biopsy and surgery in women with recently diagnosed breast cancer. Endpoints will be changes in serum and tissue biomarkers related to progression of cancer.

The effect of Polyphenon E on tumor cell c-Met expression and phosphorylation is the primary objective. Secondary objectives include the effects on the other tissue and serum biomarkers. Evaluation of the safety and tolerability of Polyphenon E in this subject population is another objective.

1.1 Determine the effects of Polyphenon E on tumor cell c-Met expression and phosphorylation levels in patients with breast cancer

1.2 Determine the effects of Polyphenon E on PI-3K activation in patients with breast cancer

1.3 Determine the effects of Polyphenon E on MAPK activation in patients with breast cancer

1.4 Determine the effects of Polyphenon E on expression levels of other proteins involved in motility and invasion such as Rho GTPases and extracellular proteinases in patients with breast cancer

1.5 Determine the effects of Polyphenon E on markers of angiogenesis in patients with breast cancer

1.6 Determine the effects of Polyphenon E on other serum markers: C-reactive protein (CRP), Insulin-Like Growth factor I (IGF-I), Insulin-like Growth Factor Binding Protein 3 (IGFBP-3) and Hepatocyte Growth Factor HGF

1.7 Evaluate the safety and tolerability of Polyphenon E in this subject population

Inclusion Criteria:

• Definitive biopsy demonstrating primary breast cancer
• Residual breast cancer requiring additional surgical resection
• Stage I, II or III disease
• Patient has ability to give signed informed consent
• Normal hepatic and renal function (creatinine<1.5, transaminases <1.5 times upper limit of normal).
• ECOG Performance status of 0 or 1.
• Age ≥ 21 years and less than 75

Exclusion Criteria:

• Prior hormonal or surgical therapy for breast cancer
• Abnormal liver function test
• Liver or kidney problems that would interfere with metabolism of study drug
• Any condition that would hamper informed consent or ability to comply with study protocol
• Participation in another research study in the last three months
• Known malignancy at any site other than breast
• Recent consumption of green tea (5 or more cups per day, within one week prior to biopsy)
• Allergy or intolerance to any component of green tea
• Inability or refusal to comply with definitive surgical therapy