Metformin Hydrochloride in Preventing Breast Cancer in Patients With Atypical Hyperplasia or In Situ Breast Cancer

Inclusion Criteria

• Qualifying cytological atypia in RPFNA, Masood score of 14-17; the qualifying RPFNA (of one or both breasts) must be send to Dr. Seewaldt's laboratory for cytological scoring and proteomic analysis; score results must be received from Dr. Seewaldt's lab prior to patient registration/randomization; test must be done =< 90 days prior to registration/randomization

  * Note: Only the contralateral breast can be aspirated in women with DCIS and those undergoing surgery for an atypical lesion; the decision to aspirate the contralateral breast is at the discretion of the woman's surgeon

• Hemoglobin >= 9 g/dL

• Absolute neutrophil count (ANC) >= 1500/mm^3

• Platelet count >= 75,000/mm^3

• Creatinine =< 1.4 mg/dL

• Total bilirubin =< 3.0 mg/dL

• Aspartate transaminase (AST) =< 3 x upper limit of normal (ULN)

• Alanine transaminase (ALT) =< 3 x ULN

• Negative pregnancy test done =< 7 days prior to registration/randomization, for women of childbearing potential only

  * A female of childbearing potential is a sexually mature female who: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally postmenopausal for at least 12 consecutive months (i.e., has had menses at any time in the preceding 12 consecutive months)

• Women eligible to take tamoxifen must be offered tamoxifen prevention as part of their clinical care and have refused tamoxifen treatment

Exclusion Criteria

• Other active malignancy =< 5 years prior to pre-registration; EXCEPTIONS: non-melanotic skin cancer or carcinoma-in-situ of the cervix; NOTE: if there is a history or prior malignancy, they must not be receiving other specific treatment, i.e., other hormonal therapy, for their cancer
• Body mass index (BMI) < 25
• Receiving Warfarin
• Bilateral breast implants or autologous breast flap reconstruction
• Active diagnosis of alcoholism
• Contraindication to metformin prevention such as acute hypersensitivity or allergic reaction to metformin
• Currently receiving tamoxifen or raloxifene
• Administration of any investigational agent =< 30 days prior to pre-registration
• Previous radiation to both breasts
• Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
• Receiving pyrimethamine, cimetidine, rifampin or cephalexin
• Women who have a core biopsy or excisional biopsy containing invasive cancer
• Women who have taken metformin within the past 90 days
• Patients with hemoglobin a1c > 6.3 or who are being actively treated for diabetes