A Phase II Trial of Lovastatin for Modification of Abnormal Breast Duct Cytology and Risk-Associated Biomarkers in Women at High Inherited Risk of Breast Cancer

Inclusion Criteria:

- Women with an increased inherited risk of breast cancer, but no current breast
cancer. Defined by either:

- Known deleterious mutation in BRCA1, BRCA2, or other high-risk mutation

- Family history conveying at least a 2-fold increase in breast cancer risk

- Only those patients without evidence of abnormality requiring biopsy on mammography,
breast MRI, or clinical breast examination will be eligible for inclusion.

- Patients must have ECOG performance status 0.

- Patients must have normal organ and marrow function, including complete blood count
and comprehensive metabolic panel within normal institutional limits.

- Patients must have no evidence of active liver disease, or elevation of serum
transaminases. Prior history of liver disease, if not currently active, will not
exclude patients from participation. Patients must have no evidence of myopathy or
myositis, including symptoms of generalized muscle aches or weakness, muscle
tenderness, or elevation in creatine phosphokinase. In order to be eligible for
participation, patients will be asked to limit alcoholic beverage consumption to
three alcoholic drinks per week. This is specified because of recommendations for
caution with use of lovastatin in patients with heavy alcohol use.

- Women of child-bearing potential must agree to use adequate contraception prior to
study entry and for the duration of study participation. Only women who are not
currently breastfeeding will be eligible to participate.

Exclusion Criteria:

- Patients with prior history of invasive breast cancer less than 2 years previously
unless they had stage III or lower breast cancer more than 2 years ago.

- Patients with history of other cancer, excluding non-melanoma skin cancer, unless the
cancer was stage III or lower, and they have been without evidence of recurrence for
5 years.

- Patients who show evidence of malignant cytology on initial rpFNA.

- Patients whose initial mammogram, breast MRI, or clinical breast exam prompts
recommendation for biopsy by study investigators.

- Patients using other investigational agents.

- Use of tamoxifen or selective estrogen response modifiers (SERMS), including
raloxifene; patients who have taken these agents within the last 2 years.

- Patients who have a history of allergic reactions attributed to compounds of similar
chemical or biologic composition to lovastatin.

- Patients with 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.

- Patients on concurrent lovastatin and cyclosporine, gemfibrozil, erythromycin,
fibrates or niacin, unless they discontinue them.