This randomized clinical trial studies metformin hydrochloride in overweight or obese patients at elevated risk for breast cancer. Metformin hydrochloride may decrease the expression of early tumor makers in breast tissue of patients at increased risk for breast cancer
PRIMARY OBJECTIVES: I. To determine the changes in the signal pathway profiling of breast tissue using reverse phase proteomics in tissue biopsy of overweight or obese women at elevated risk for breast cancer treated with metformin (metformin hydrochloride) (850mg orally twice a day) for 12 cycles. SECONDARY OBJECTIVES: I. To determine the effect of metformin on breast tissue density of overweight or obese women at elevated risk for breast cancer using qualitative mammographic fat density criteria. II. To determine the effect of metformin on the insulin axis in serum of overweight or obese women at elevated risk for breast cancer treated with metformin (850mg orally twice a day) for 12 cycles. III. To determine the toxicities associated with metformin. OUTLINE: Patients are randomized to 1 of 2 treatment arms. ARM I: Patients receive metformin hydrochloride by mouth once daily on days 1-30 in course 1 and twice daily on days 1-30 thereafter. Treatment repeats every 30 days for 12 courses in the absence of disease progression or unacceptable toxicity. ARM II: Patients receive placebo by mouth once daily on days 1-30 in course 1 and twice daily on days 1-30 thereafter. Treatment repeats every 30 days for 12 courses in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 6 months for up to 5 years.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
PREVENTION
Masking
DOUBLE
Enrollment
24
Indiana University Melvin and Bren Simon Cancer Center
Indianapolis, Indiana, United States
Changes in the phosphorylation of proteins after metformin exposure
Reverse phase proteomic assays (RPPA) will be performed to measure changes in the phosphorylation of proteins after metformin exposure. Changes in the phosphorylation of proteins after metformin exposure will be calculated and compared using two-sample t-tests. As a supplemental analysis, analysis of covariance (ANCOVA) will be used to model the 12 month levels adjusted for baseline. Assumptions for analysis will be checked and non-parametric methods used if needed; however it is expected that the data will be normally distributed on the log scale.
Time frame: Baseline and 12 months
Changes in ordinal level of breast density
Changes in ordinal level of breast density will be performed using the breast density criteria previously established by Boyd and colleagues (New England Journal of Medicine 2007). Each image will be grouped into one of six categories: 0%, \<10%, 10-25%, 25-50%, 50-75% and \>75%. Changes will be compared between the two groups using Wilcoxon Rank-Sum tests.
Time frame: Baseline and 12 months
Proportion of patients experiencing adverse events assessed using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0
Will be tabulated by arm and grade.
Time frame: Up to 30 days
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