Trial Outcomes & Findings for Phase 2 Study of Lovastatin as Breast Cancer Chemoprevention (NCT NCT00285857)

Results Overview

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.

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

30 participants

Primary outcome timeframe

6 months

Results posted on

2017-03-09

Participant Flow

Participant milestones

Participant milestones
Measure	Lovastatin 80 mg/Day Lovastatin 80 mg/day given as 40 mg orally twice per day
Overall Study STARTED	30
Overall Study COMPLETED	26
Overall Study NOT COMPLETED	4

Reasons for withdrawal

Reasons for withdrawal
Measure	Lovastatin 80 mg/Day Lovastatin 80 mg/day given as 40 mg orally twice per day
Overall Study Withdrawal by Subject	2
Overall Study Inadequate initial breast cytology	1
Overall Study Adverse Event	1

Baseline Characteristics

Phase 2 Study of Lovastatin as Breast Cancer Chemoprevention

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Lovastatin n=30 Participants Lovastatin: 80 mg; 40 mg orally twice per day
Age, Categorical <=18 years	0 Participants n=39 Participants
Age, Categorical Between 18 and 65 years	30 Participants n=39 Participants
Age, Categorical >=65 years	0 Participants n=39 Participants
Age, Continuous	45 years n=39 Participants
Sex: Female, Male Female	30 Participants n=39 Participants
Sex: Female, Male Male	0 Participants n=39 Participants
Region of Enrollment United States	30 participants n=39 Participants

PRIMARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Baseline Non-proliferative Breast Disease (NPBD) n=13 Participants Those subjects whose pre-treatment evaluation by RPFNA (random periareolar fine needle aspiration) returned a diagnosis of non-proliferative breast disease	Baseline Proliferative Breast Disease Without Atypia (PBD-A) n=12 Participants Those subjects whose pre-treatment evaluation by RPFNA (random periareolar fine needle aspiration) returned a diagnosis of proliferative breast disease without atypia	Baseline Proliferative Breast Disease With Atypia (PBD+A) Those subjects whose pre-treatment evaluation by RPFNA (random periareolar fine needle aspiration) returned a diagnosis of proliferative breast disease with atypia	Baseline Carcinoma in Situ or Invasive Cancer (CIS/IC) Those subjects whose pre-treatment evaluation by RPFNA (random periareolar fine needle aspiration) returned a diagnosis of carcinoma in situ or invasive cancer	Baseline Biopsy Acellular n=1 Participants Those subjects whose pre-treatment evaluation by RPFNA (random periareolar fine needle aspiration) generated a sample that was acellular
Change in the Incidence of Abnormal Breast Duct Cytology After Treatment With Lovastatin 80 mg/Day Post-treatment PBD-A	2 participants	7 participants	—	—	0 participants
Change in the Incidence of Abnormal Breast Duct Cytology After Treatment With Lovastatin 80 mg/Day Post-treatment NPBD	8 participants	5 participants	—	—	1 participants
Change in the Incidence of Abnormal Breast Duct Cytology After Treatment With Lovastatin 80 mg/Day Post-treatment PBD+A	0 participants	0 participants	—	—	0 participants
Change in the Incidence of Abnormal Breast Duct Cytology After Treatment With Lovastatin 80 mg/Day Post-treatment CIS/IC	0 participants	0 participants	—	—	0 participants
Change in the Incidence of Abnormal Breast Duct Cytology After Treatment With Lovastatin 80 mg/Day Post-treatment biopsy acellular	3 participants	0 participants	—	—	0 participants

SECONDARY outcome

Timeframe: 6 months

Population: Outcome reported as the change in mean mammographic density with standard deviation (SD) of the post-treatment measurements.

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

Outcome measures

Outcome measures
Measure	Baseline Non-proliferative Breast Disease (NPBD) n=30 Participants Those subjects whose pre-treatment evaluation by RPFNA (random periareolar fine needle aspiration) returned a diagnosis of non-proliferative breast disease	Baseline Proliferative Breast Disease Without Atypia (PBD-A) Those subjects whose pre-treatment evaluation by RPFNA (random periareolar fine needle aspiration) returned a diagnosis of proliferative breast disease without atypia	Baseline Proliferative Breast Disease With Atypia (PBD+A) Those subjects whose pre-treatment evaluation by RPFNA (random periareolar fine needle aspiration) returned a diagnosis of proliferative breast disease with atypia	Baseline Carcinoma in Situ or Invasive Cancer (CIS/IC) Those subjects whose pre-treatment evaluation by RPFNA (random periareolar fine needle aspiration) returned a diagnosis of carcinoma in situ or invasive cancer	Baseline Biopsy Acellular Those subjects whose pre-treatment evaluation by RPFNA (random periareolar fine needle aspiration) generated a sample that was acellular
Change in Mammographic Density Before and After Treatment With Lovastatin 80 mg/Day	-0.10 BI-RADS Standard Deviation 1.08	—	—	—	—

SECONDARY outcome

Timeframe: 6 months

Outcome measures

Outcome measures
Measure	Baseline Non-proliferative Breast Disease (NPBD) n=25 Participants Those subjects whose pre-treatment evaluation by RPFNA (random periareolar fine needle aspiration) returned a diagnosis of non-proliferative breast disease	Baseline Proliferative Breast Disease Without Atypia (PBD-A) Those subjects whose pre-treatment evaluation by RPFNA (random periareolar fine needle aspiration) returned a diagnosis of proliferative breast disease without atypia	Baseline Proliferative Breast Disease With Atypia (PBD+A) Those subjects whose pre-treatment evaluation by RPFNA (random periareolar fine needle aspiration) returned a diagnosis of proliferative breast disease with atypia	Baseline Carcinoma in Situ or Invasive Cancer (CIS/IC) Those subjects whose pre-treatment evaluation by RPFNA (random periareolar fine needle aspiration) returned a diagnosis of carcinoma in situ or invasive cancer	Baseline Biopsy Acellular Those subjects whose pre-treatment evaluation by RPFNA (random periareolar fine needle aspiration) generated a sample that was acellular
Change in Total Cholesterol After Treatment With Lovastatin 80 mg/Day	-8 mg/dL Standard Deviation 45.7	—	—	—	—

SECONDARY outcome

Timeframe: 6 months

Population: Change in mean of LDL level, with standard deviation of the values at

Outcome measures

Outcome measures
Measure	Baseline Non-proliferative Breast Disease (NPBD) n=26 Participants Those subjects whose pre-treatment evaluation by RPFNA (random periareolar fine needle aspiration) returned a diagnosis of non-proliferative breast disease	Baseline Proliferative Breast Disease Without Atypia (PBD-A) Those subjects whose pre-treatment evaluation by RPFNA (random periareolar fine needle aspiration) returned a diagnosis of proliferative breast disease without atypia	Baseline Proliferative Breast Disease With Atypia (PBD+A) Those subjects whose pre-treatment evaluation by RPFNA (random periareolar fine needle aspiration) returned a diagnosis of proliferative breast disease with atypia	Baseline Carcinoma in Situ or Invasive Cancer (CIS/IC) Those subjects whose pre-treatment evaluation by RPFNA (random periareolar fine needle aspiration) returned a diagnosis of carcinoma in situ or invasive cancer	Baseline Biopsy Acellular Those subjects whose pre-treatment evaluation by RPFNA (random periareolar fine needle aspiration) generated a sample that was acellular
Change in Low Density Lipoprotein (LDL) After Treatment With Lovastatin 80 mg/Day	-6 mg/dL Standard Deviation 32.1	—	—	—	—

Adverse Events

Lovastatin

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Lovastatin n=30 participants at risk Lovastatin: 80 mg; 40 mg orally twice per day
Musculoskeletal and connective tissue disorders Myalgia	3.3% 1/30 • Number of events 1
Musculoskeletal and connective tissue disorders Arthralgia	3.3% 1/30 • Number of events 1
Gastrointestinal disorders Dyspepsia	3.3% 1/30 • Number of events 1

Additional Information

James M. Ford

Stanford University

Phone: (650) 498-6689

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place