Breast Cancer
Conditions
Keywords
duct cytology
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
Interventions
DRUGLovastatin
Lovastatin 80 mg/day as 40 mg orally twice daily. Lovastatin is approved by FDA as a cholesterol-lowering agent.
Sponsors
Stanford University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 65 Years
Healthy volunteers
No
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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 | — |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Lovastatin Lovastatin: 80 mg; 40 mg orally twice per day | 30 |
| Total | 30 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 1 |
| Overall Study | Inadequate initial breast cytology | 1 |
| Overall Study | Withdrawal by Subject | 2 |
Baseline characteristics
| Characteristic | Lovastatin |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 30 Participants |
| Age, Continuous | 45 years |
| Region of Enrollment United States | 30 participants |
| Sex: Female, Male Female | 30 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 3 / 30 |
| serious Total, serious adverse events | 0 / 30 |
Outcome results
Primary
Change in the Incidence of Abnormal Breast Duct Cytology After Treatment With Lovastatin 80 mg/Day
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.
Time frame: 6 months
Population: Participants either at least one of the following:~* Deleterious germline mutation in BRCA1, BRCA2, CDH1, or TP53~* Lifetime breast cancer risk of breast cancer of 20 % as estimated by the Claus model~* Personal history of estrogen receptor andprogesterone receptor-negative breast cancer.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Baseline Non-proliferative Breast Disease (NPBD) | Change in the Incidence of Abnormal Breast Duct Cytology After Treatment With Lovastatin 80 mg/Day | Post-treatment CIS/IC | 0 participants |
| Baseline Non-proliferative Breast Disease (NPBD) | Change in the Incidence of Abnormal Breast Duct Cytology After Treatment With Lovastatin 80 mg/Day | Post-treatment PBD+A | 0 participants |
| Baseline Non-proliferative Breast Disease (NPBD) | Change in the Incidence of Abnormal Breast Duct Cytology After Treatment With Lovastatin 80 mg/Day | Post-treatment NPBD | 8 participants |
| Baseline Non-proliferative Breast Disease (NPBD) | Change in the Incidence of Abnormal Breast Duct Cytology After Treatment With Lovastatin 80 mg/Day | Post-treatment PBD-A | 2 participants |
| Baseline Non-proliferative Breast Disease (NPBD) | Change in the Incidence of Abnormal Breast Duct Cytology After Treatment With Lovastatin 80 mg/Day | Post-treatment biopsy acellular | 3 participants |
| Baseline Proliferative Breast Disease Without Atypia (PBD-A) | Change in the Incidence of Abnormal Breast Duct Cytology After Treatment With Lovastatin 80 mg/Day | Post-treatment PBD+A | 0 participants |
| Baseline Proliferative Breast Disease Without Atypia (PBD-A) | Change in the Incidence of Abnormal Breast Duct Cytology After Treatment With Lovastatin 80 mg/Day | Post-treatment NPBD | 5 participants |
| Baseline Proliferative Breast Disease Without Atypia (PBD-A) | Change in the Incidence of Abnormal Breast Duct Cytology After Treatment With Lovastatin 80 mg/Day | Post-treatment PBD-A | 7 participants |
| Baseline Proliferative Breast Disease Without Atypia (PBD-A) | Change in the Incidence of Abnormal Breast Duct Cytology After Treatment With Lovastatin 80 mg/Day | Post-treatment CIS/IC | 0 participants |
| Baseline Proliferative Breast Disease Without Atypia (PBD-A) | Change in the Incidence of Abnormal Breast Duct Cytology After Treatment With Lovastatin 80 mg/Day | Post-treatment biopsy acellular | 0 participants |
| Baseline Biopsy Acellular | Change in the Incidence of Abnormal Breast Duct Cytology After Treatment With Lovastatin 80 mg/Day | Post-treatment biopsy acellular | 0 participants |
| Baseline Biopsy Acellular | Change in the Incidence of Abnormal Breast Duct Cytology After Treatment With Lovastatin 80 mg/Day | Post-treatment CIS/IC | 0 participants |
| Baseline Biopsy Acellular | Change in the Incidence of Abnormal Breast Duct Cytology After Treatment With Lovastatin 80 mg/Day | Post-treatment NPBD | 1 participants |
| Baseline Biopsy Acellular | Change in the Incidence of Abnormal Breast Duct Cytology After Treatment With Lovastatin 80 mg/Day | Post-treatment PBD+A | 0 participants |
| Baseline Biopsy Acellular | Change in the Incidence of Abnormal Breast Duct Cytology After Treatment With Lovastatin 80 mg/Day | Post-treatment PBD-A | 0 participants |
Secondary
Change in Low Density Lipoprotein (LDL) After Treatment With Lovastatin 80 mg/Day
Time frame: 6 months
Population: Change in mean of LDL level, with standard deviation of the values at
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Baseline Non-proliferative Breast Disease (NPBD) | Change in Low Density Lipoprotein (LDL) After Treatment With Lovastatin 80 mg/Day | -6 mg/dL | Standard Deviation 32.1 |
Secondary
Change in Mammographic Density Before and After Treatment With Lovastatin 80 mg/Day
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
Time frame: 6 months
Population: Outcome reported as the change in mean mammographic density with standard deviation (SD) of the post-treatment measurements.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Baseline Non-proliferative Breast Disease (NPBD) | Change in Mammographic Density Before and After Treatment With Lovastatin 80 mg/Day | -0.10 BI-RADS | Standard Deviation 1.08 |
Secondary
Change in Total Cholesterol After Treatment With Lovastatin 80 mg/Day
Time frame: 6 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Baseline Non-proliferative Breast Disease (NPBD) | Change in Total Cholesterol After Treatment With Lovastatin 80 mg/Day | -8 mg/dL | Standard Deviation 45.7 |