Phase II Study of Metformin for Reduction of Obesity-Associated Breast Cancer Risk
Condition: Breast Cancer Prevention
MeSH terms: Breast Neoplasms
Intervention: Metformin; Placebo
Intervention description: 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)
Intervention MeSH terms: Metformin
Phase: Phase 2
Study type: Interventional
Primary purpose: Prevention
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 151.0
Sex: Female
Minimum age: 21 Years
Maximum age: 54 Years
Healthy volunteers: No
Keywords: Breast cancer prevention; metformin; Breast cancer risk reduction

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.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Premenopausal women

          -  21-54 years of age

          -  Have a BMI of 25 kg/m2 or greater

          -  No change in menstrual patterns for the past 6 months preceding the time of
             registration

          -  Waist circumference ≥ 35 inches or ≥ 31 inches for Asian Americans, individuals with
             polycystic ovary syndrome, or individuals with non-alcoholic fatty liver disease.

          -  Have at least one other component of metabolic syndrome (103) reported below:

               -  Elevated triglycerides (≥ 150 mg/dL (1.7 mmol/L) or on drug treatment for
                  elevated triglycerides

               -  Reduced HDL-C (< 50 mg/dL (1.3 mmol/L) or on drug treatment for reduced HDL-C

               -  Elevated blood pressure (≥ 130 Hg systolic blood pressure or ≥85 mm Hg diastolic
                  blood pressure or on antihypertensive drug treatment in a patient with a history
                  of hypertension

               -  Elevated fasting glucose (≥100 mg/dL)

          -  Mammogram negative for breast cancer within the 12 months preceding the time of
             registration for women ≥ 50 years of age

          -  Ability to understand and the willingness to sign a written informed consent document

        Exclusion Criteria:

          -  Postmenopausal women

               -  Amenorrhea for at least 12 months (preceding the time of registration), or

               -  History of hysterectomy and bilateral salpingo-oophorectomy, or

               -  At least 55 years of age with prior hysterectomy with or without oophorectomy, or

               -  Age 35 to 54 with a prior hysterectomy without oophorectomy OR with a status of
                  ovaries unknown with documented follicle-stimulating hormone level demonstrating
                  elevation in postmenopausal range

          -  Women who are pregnant, planning pregnancy within the next year, or breastfeeding

          -  On treatment with any drug for diabetes

          -  Have uncontrolled intercurrent illness including, but not limited to, ongoing or
             active infection, symptomatic congestive heart failure, unstable angina pectoris,
             cardiac arrhythmia, or any illness that would limit compliance with study requirements

          -  Have received chemotherapy and/or radiation for any malignancy (excluding non-melanoma
             skin cancer and cancers confined to organs with removal as only treatment) in the past
             5 years (preceding the time of registration)

          -  Have received other investigational agents within the past 3 months (preceding the
             time of registration)

          -  Have a history of lactic acidosis or risk factors for lactic acidosis

          -  Have significant renal disease or dysfunction (creatinine ≥ 1.4 mg/dL)

          -  Have significant hepatic dysfunction (bilirubin ≥ 1.5 x ULN unless with Gilberts
             syndrome or AST/ALT ≥ 3 x ULN)

          -  Have a history of alcoholism or high alcohol consumption (average of > 3 standard
             drinks/day)

          -  Have a history of allergic reactions to metformin or similar drugs

          -  Have a history of severe claustrophobia

          -  Have electrically, magnetically, or mechanically activated implants including cardiac
             pacemaker, cochlear implants, magnetic surgical clips or prostheses

          -  Have breast implants