Phase 2 Study of Lovastatin as Breast Cancer Chemoprevention

Phase 2

Terminated

Brief Summary: 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.

Detailed Description: 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

Recruitment & Eligibility

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Arm && Interventions

Group	Intervention	Description
Lovastatin 80 mg/day	Lovastatin	Lovastatin 80 mg/day as 40 mg orally twice daily, for 6 months.

Primary Outcome Measures

Name	Time	Method
Change in the Incidence of Abnormal Breast Duct Cytology After Treatment With Lovastatin 80 mg/Day	6 months	Assessed on that basis of pre- and post-treatment evaluation with RPFNA (random periareolar fine needle aspiration). All subjects received a prescription for lovastatin 80 mg/day, to be taken as 40 mg twice-a-day. Cytology was qualitatively and quantitatively, using the Masood semiquantitative scale to assign a number to each specimen, with higher numbers indicating increasing degrees of abnormality, as follows: 06-10 Non-proliferative breast disease (NPBD) 11-14 Proliferative breast disease without atypia (PBD-A) 15-18 Proliferative breast disease with atypia (PBD+A) 19-24 Carcinoma in situ and invasive cancer (CIS/IC) If no cells could be obtained after multiple RPFNA attempts, the classification was acellular. Change from NPBD to PBD-A was considered Unfavorable. Change from NPBD to Acellular was considered Equivocal. Change from PBD-A to NPBD was considered Favorable.

Secondary Outcome Measures

Name	Time	Method
Change in Mammographic Density Before and After Treatment With Lovastatin 80 mg/Day	6 months	Bilateral mammography was performed at study entry (before lovastatin therapy) and at study conclusion (after lovastatin therapy) . Mammograms were assessed for a decline in mean breast density, using the American College of Radiology Breast Imaging Reporting and Data System (BI-RAD) composition system for mammographic density assessment. Category 0 Need additional imaging evaluation 1. Negative 2. Benign 3. Probably benign 4. Suspicious abnormality 5. Highly suggestive of malignancy 6. Known biopsy-proven malignancy
Change in Total Cholesterol After Treatment With Lovastatin 80 mg/Day	6 months
Change in Low Density Lipoprotein (LDL) After Treatment With Lovastatin 80 mg/Day	6 months