Phase II Study of Metformin for Reduction of Obesity-Associated Breast Cancer Risk
Condition: Breast Cancer Prevention
MeSH terms: Breast Neoplasms
Study type: Interventional
Phase: Phase 2

Summary: 
      Overweight and obesity are well established risk factors for breast cancer that develop after
      menopause. The increased postmenopausal breast cancer risk in women who are overweight or
      obese is likely to be attributed to multiple metabolic disturbances. Metformin is a commonly
      used medication in diabetics to stabilize blood sugar. Association studies and laboratory
      studies have shown its potential to reduce the risk for development of cancer, including
      breast cancer. Recent pilot clinical studies in breast cancer patients suggest that metformin
      may only be effective in overweight or obese women with metabolic disturbances. We propose to
      conduct a clinical study of metformin in overweight or obese premenopausal women with
      metabolic disturbances. Study participants will be randomly assigned to receive metformin or
      placebo for 12 months. The study will evaluate whether metformin can result in favorable
      changes in risk features that have been associated with increased breast cancer risk. The
      risk features that will be examined in our study include breast density, certain proteins and
      hormones, products of body metabolism, and body weight and composition. The study should help
      determine the potential breast cancer preventive activity of metformin in a growing
      population at risk for multiple diseases.
    

Detailed description: 
      High adiposity is a major risk factor for a number of chronic diseases, including type 2
      diabetes, cardiovascular diseases, and certain types of cancer, including postmenopausal
      breast cancer. The increased postmenopausal breast cancer risk in women with high adiposity
      is likely to be attributed to multiple metabolic disturbances including altered circulating
      sex steroid hormones, hyperinsulinemic insulin resistance, altered expression and secretion
      of adipokines from adipose tissue, increased production of pro-inflammatory cytokines, and
      increased oxidative stress.

      Metformin, a widely used antidiabetic drug, exerts favorable effects on multiple metabolic
      disturbances which may lead to reduction of breast cancer risk in women with high adiposity.
      In addition, metformin may exert a direct effect in mammary tissue through the activation of
      the AMP-activated protein kinase signaling pathway, leading to an antiproliferative effect
      and induction of apoptosis. Recent case control and cohort studies found that treatment with
      metformin appears to substantially reduce the risk for development of cancer in diabetics,
      including breast cancer. There are a number of ongoing clinical trials of metformin in breast
      cancer patients. However, applicability of these trials to at risk healthy women requires
      further research and the concurrent or prior cancer treatments in these trials hinder the
      evaluation of metformin as a single agent for breast cancer risk reduction. In addition,
      recent clinical and animal studies suggest that metformin may only exert tumor suppressive
      effects in metabolic phenotypes of high adiposity and metabolic disturbances.

      A Phase II randomized, double-blind, placebo-controlled trial of metformin in
      overweight/obese premenopausal women who have metabolic syndrome will be conducted. This
      study population is at increased risk for postmenopausal breast cancer and has a high
      prevalence of metabolic disturbances. The overall objective of this study is to determine its
      potential effects on reduction of obesity-associated breast cancer risk.
    

Intervention name(s): Metformin; Placebo
Intervention type(s): Drug; Drug
Intervention description(s): metformin 850 mg 1 tablet taken by mouth daily X 4 weeks, then metformin 850 mg 1 tablet taken twice daily for the duration of he intervention period.; 1 tablet daily by mouth X 4 weeks, then 1 tablet twice daily by mouth for the remaining duration of the trial (12 months)
Other intervention name(s): Glucophage; Glumetza; Fortamet
Intervention MeSH terms: Metformin
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Prevention
Keywords: Breast cancer prevention; metformin; Breast cancer risk reduction