Phase 2 Study of Lovastatin as Breast Cancer Chemoprevention

A Phase 2 Trial of Lovastatin for Modification of Abnormal Breast Duct Cytology and Risk-Associated Biomarkers in Women at High Inherited Risk of Breast Cancer

The study evaluates if a 6-month course of oral lovastatin at 80 mg/day would decrease abnormal breast duct cytology in women with a high inherited breast cancer risk.

The study evaluates if a 6-month course of oral lovastatin at 80 mg/day (as 40 mg twice-a-day) would decrease abnormal breast duct cytology in women with a high inherited breast cancer risk. Breast duct cytology was assessed as hyperplasia or hyperplasia with atypia, as measured by random periareolar fine needle aspiration (rpFNA), of breast duct cells.

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

• Asess incidence of breast cancers and new high-risk breast lesions, including atypical hyperplasia, ductal or lobular carcinoma in situ, or radial scar.

• 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

INCLUSION CRITERIA

• Female

• Increased inherited risk of breast cancer, as defined by:

  • Known deleterious mutation in BRCA1, BRCA2, or other high-risk mutation
  • Family history conveying at least a 2-fold increase in breast cancer risk

• ECOG performance status 0

• Normal organ and marrow function, including complete blood count and comprehensive metabolic panel within normal institutional limits

• Subject agreement to limit alcoholic beverage consumption to three alcoholic drinks per week.

EXCLUSION CRITERIA

• Prior history of invasive breast cancer less than 2 years previously (EXCEPTION: stage III or lower breast cancer > 2 years ago)
• Current or history of other cancers (EXCEPTION: non-melanoma skin cancer, or stage III or cancer without evidence of recurrence for 5 years
• Initial mammogram, breast MRI, or clinical breast examination prompts recommendation for biopsy by study investigators.
• Evidence of malignant cytology on initial rpFNA.
• Use of other investigational agents.
• Use of tamoxifen or selective estrogen response modifiers (SERMS), including raloxifene, within the last 2 years.
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to lovastatin.
• 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.
• Currently receiving lovastatin and cyclosporine, gemfibrozil, erythromycin, fibrates or niacin, (unless discontinued for study participation)
• No evidence of active liver disease, nor elevation of serum transaminases (prior history of liver disease, if not currently active, is not an exclusion)
• No evidence of myopathy or myositis, including symptoms of generalized muscle aches or weakness, muscle tenderness, or elevation in creatine phosphokinase.
• Lactating (breastfeeding)