Official Title: “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”

The purpose of the study is to determine whether oral lovastatin, used for 6 months, results in a decrease of abnormal breast duct cytology in women at high inherited breast cancer risk.

Study Type: Interventional

Study Design: Treatment, Non-Randomized, Open Label, Uncontrolled, Single Group Assignment, Safety/Efficacy Study

The purpose of the study is to determine whether oral lovastatin, given daily at a dose of 80 mg for six months, results in a decrease in the rate of abnormal breast duct cytology (either hyperplasia or hyperplasia with atypia as measured by random periareolar fine needle aspiration (rpFNA) of breast duct cells) in women at high inherited breast cancer risk. A stratified analysis of this objective will be performed according to BRCA mutation status (absence or presence of an inherited deleterious BRCA1 or BRCA2 mutation).

Additional objectives of the study are: - To assess change in mammographic density, which is known to associate with breast cancer risk, before and after treatment with lovastatin - To assess incidence of breast cancers and new high-risk breast lesions, including atypical hyperplasia, ductal or lobular carcinoma in situ, or radial scar. - To assess change in other breast cancer risk-associated biomarkers in rpFNA specimens, including: - Ki-67 (a marker of cell proliferation) - Estrogen receptor (ER) - Progesterone receptor (PR) - HER/2-neu over-expression - Susceptibility to DNA damage

Intervention(s) in this Clinical Trial

• Drug: Lovastatin

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.

Gender Eligibility for this Clinical Trial: Female

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: 65 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: Stanford University

Overall Clinical Trial Officials and Contacts

James Ford, MD Principal Investigator Stanford University  

Overall Contact: Meredith Mills 650-724-5223 bluett@stanford.edu

Information obtained from ClinicalTrials.gov on July 02, 2009

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00285857

Study ID Number: BRSNSTU0010

ClinicalTrials.gov Identifier: NCT00285857

Health Authority: United States: Food and Drug Administration