Metformin and Omega-3 Fatty Acids in Woman With a History of Early Stage Breast Cancer

Metformin is a medication used to treat and prevent diabetes and omega-3 fatty acids has been
shown to lower cholesterol and improve cardiovascular health. Research has shown that
Metformin and omega-3 fatty acids may also be effective in preventing cancer. In this study,
we want to find out what effects, good and/or bad, the Metformin and omega-3 fatty acids
combination has on you and your risk of developing a new breast cancer.

Inclusion Criteria:

- History of histologically-confirmed stage 0, I, II, or III breast carcinoma without
evidence of disease at trial entry. Participants with a resected local recurrence are
eligible

- Minimum of 6 months since last chemotherapy, biologic therapy (i.e., trastuzumab),
radiation therapy, and/or breast surgery and no evidence of recurrent disease

- Minimum of 6 months since completion of adjuvant tamoxifen (tamoxifen is known to
lower mammographic density119-121). Current use of a third generation aromatase
inhibitor [AI] (i.e., anastrozole, letrozole, exemestane) is permitted provided that
the participant has been on a stable dose for the past 6 months

- Age 21 to 75 years. Both pre- and postmenopausal women will be included in this study.
We will exclude perimenopausal women, defined as menstrual cycle irregularity
(variable cycle length that differs from normal by more than 7 days) and an
Follicle-Stimulating Hormone (FSH) greater than 20 mili international units

- Negative serum pregnancy testing

- Normal mammogram of the contralateral breast within the past 12 months, defined as no
new suspicious calcifications or other abnormal findings warranting a breast biopsy

- Eastern Cooperative Oncology Group (ECOG) performance status less than 2

- Participants must have normal organ and marrow function within 28 days prior to
randomization

- Body mass index (BMI) greater than or equal to 25 kilograms per meter squared or
baseline fasting glucose of less than 126 milligrams per deciliter

- Participants must have a baseline mammographic density greater than or equal to 25
percent based upon the Breast Imaging Reporting and Data System (BIRADS) density score
of 2, 3, or 4. Women with a baseline mammographic density of less than 25 percent
(BIRADS Score= 1) will not be eligible

- Willingness to abstain from all omega-3 fish oil supplements for 30 days prior to
baseline evaluation and during the study intervention

- Willingness to comply with all study interventions and follow-up procedures

- Ability to understand and willingness to sign a written informed consent document

Exclusion Criteria:

- History of histologically-confirmed bilateral breast cancer

- History of or plans for bilateral mastectomies

- Evidence of metastatic breast cancer

- Prior radiation therapy or implant in the contralateral breast

- Known diabetes (type 1 or 2) or baseline fasting glucose greater than 126 milligrams
per deciliter

- Any condition associated with increased risk of metformin-associated lactic acidosis
(e.g., congestive heart failure defined as New York Heart Association [NYHA] Class III
or IV functional status, history of acidosis of any type, intake of 3 or more
alcoholic beverages per day on average over the past 6 months)

- Currently taking metformin, sulfonylureas, thiazolidinediones, or insulin for any
reason

- History of allergic reactions attributed to compounds of similar chemical or biologic
composition to metformin or omega-3 fatty acids

- Receiving hormone replacement therapy, tamoxifen, or raloxifene within 6 months of
trial entry

- Participants may not be receiving any other investigational agents for 30 days prior
to baseline evaluation and during the study intervention

- Any omega-3 fatty acids should not be taken for 30 days prior to baseline evaluation
and during the study intervention. If participants are consuming any of these items
and would like to participate in this study, then a 30-day washout period will be
required. - Uncontrolled or significant co-morbid illness patients receiving active
chemotherapy or radiotherapy; or psychiatric illness/social situations that would
limit compliance with study requirements