Pre-Surgical Trial of Metformin in Patients With Operable Breast Cancer
- To determine the in situ effects of metformin hydrochloride on proliferation (Ki67) and
apoptosis (caspase-3) in women with operable stage I or II breast cancer.
- To determine the in situ biologic effect of metformin hydrochloride on the AMP kinase,
MTOR/PI3K, and IGF pathways in breast cancer (tissue S6K and phospho S6K, p53, p63, and
p73 levels as well as p53 [(Ser-15), if wild-type p53 is present], p63 [Ser-66/68,
Ser-301, and Ser-361], and p73 [Y-99] phosphorylation, PTEN [clone 6H2.1], phospho-Akt
[S473], insulin receptor substrate 1 and 2 [IRS-1 and IRS-2], and LKB1).
- To determine if molecular classification (basal-type vs luminal A vs luminal B) and the
established p63 and p73 RNA microarray gene signatures correlate with the metformin
hydrochloride-induced effects on proliferation (Ki67), apoptosis (caspase-3) and the
selected biomarkers (listed above) in breast cancer.
- To collect and analyze pre- and post-treatment peripheral blood specimens for serum
glucose and insulin levels, as well as circulating IGF-1 and IGF binding protein 3
OUTLINE: Patients receive oral metformin hydrochloride twice daily for 7-21 days.
Approximately 24-36 hours after the last dose of metformin hydrochloride, patients undergo
surgical resection (total mastectomy or segmental resection with lymph node evaluation) of
Patients undergo blood and tissue sample collection periodically for biomarker analysis.
Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Change in Ki67 Levels Before and After Treatment
Change in Ki67 levels in pre-treatment, pre-surgery and post-treatment, surgically excised breast tissue. Measured by percentage of positive-staining nuclei with a minimum of 0% to a maximum of 100%. A mean score is determined.
baseline and between 8-23 days
Ingrid Mayer, M.D.
Vanderbilt-Ingram Cancer Center
United States: Food and Drug Administration
VICC BRE 0942
|Vanderbilt-Ingram Cancer Center||Nashville, Tennessee 37232-6838|
|Emory University Hospital||Atlanta, Georgia 30322|
|Vanderbilt-Ingram Cancer Center - Cool Springs||Nashville, Tennessee 37064|