Trial Outcomes & Findings for Aging Mammary Stem Cells and Breast Cancer Prevention (NCT NCT02642094)

NCT ID: NCT02642094

Last Updated: 2023-12-05

Results Overview

Comparing biopsy tissues before the treatment with surgical samples after rapamycin treatment in the same individuals to determine percentage nuclei with positive staining for Ki67 in the CCIS lesions.

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

58 participants

Primary outcome timeframe

Baseline to 5-7 day rapamycin plus 3-7 day washout

Results posted on

2023-12-05

Participant Flow

We acquired primary tissue samples from patients diagnosed with non-invasive lesions as detected by clinical pathology at the University of Texas Health Science Center at San Antonio (UTHSCSA) (San Antonio, TX). Inclusion criteria and exclusion criteria were descried in the study.

Participant milestones

Participant milestones
Measure	Rapamycin Treatment Group Patients with stage zero breast cancer were given a low dose of rapamycin at 2 mg/day for 5-7 days of treatment. A surgical specimen will be taken 3-7 days after the last dose of rapamycin. The specimens were evaluated with IHC (ImmunoHistoChemistry) for cancer progression biomarkers including p16, COX2 (cyclooxygenase-2), and Ki-67. Specimens were tested for rapamycin treatment on the properties of mammary stem/progenitor cells as another biomarker for gauging the efficacy of rapamycin treatment. A total of 40 patients were consented to undergo treatment and 38 successfully completed the regiment. The control group included 12 patients with DCIS or ADH, who declined to participate in the sirolimus study but agreed to donate their tissues, and 6 patients with invasive ductal carcinoma for a total of 18 controls. Rapamycin: Low dose of rapamycin at 2 mg/day for -5-7 days of treatment	Un-treated Control Group Subjects that consented to provide tissue, but were not treated with Rapamycin
Overall Study STARTED	40	18
Overall Study COMPLETED	38	18
Overall Study NOT COMPLETED	2	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Aging Mammary Stem Cells and Breast Cancer Prevention

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Rapamycin Treatment Group n=40 Participants A total of 40 patients were consented to undergo treatment and 38 successfully completed the regiment.	Un-treated Control Group n=18 Participants The control group included 12 patients with DCIS or ADH, who declined to participate in the sirolimus study but agreed to donate their tissues, and 6 patients with invasive ductal carcinoma for a total of 18 controls	Total n=58 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Age, Categorical Between 18 and 65 years	29 Participants n=93 Participants	3 Participants n=4 Participants	32 Participants n=27 Participants
Age, Categorical >=65 years	11 Participants n=93 Participants	15 Participants n=4 Participants	26 Participants n=27 Participants
Sex: Female, Male Female	40 Participants n=93 Participants	18 Participants n=4 Participants	58 Participants n=27 Participants
Sex: Female, Male Male	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	24 Participants n=93 Participants	9 Participants n=4 Participants	33 Participants n=27 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	14 Participants n=93 Participants	8 Participants n=4 Participants	22 Participants n=27 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	2 Participants n=93 Participants	1 Participants n=4 Participants	3 Participants n=27 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Race (NIH/OMB) Asian	1 Participants n=93 Participants	0 Participants n=4 Participants	1 Participants n=27 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Race (NIH/OMB) Black or African American	5 Participants n=93 Participants	2 Participants n=4 Participants	7 Participants n=27 Participants
Race (NIH/OMB) White	33 Participants n=93 Participants	15 Participants n=4 Participants	48 Participants n=27 Participants
Race (NIH/OMB) More than one race	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants n=93 Participants	1 Participants n=4 Participants	2 Participants n=27 Participants
Region of Enrollment United States	40 participants n=93 Participants	18 participants n=4 Participants	58 participants n=27 Participants

PRIMARY outcome

Timeframe: Baseline to 5-7 day rapamycin plus 3-7 day washout

Population: Tissue samples were randomly selected from 12 patients with DCIS who participated in the treatment study

Outcome measures

Outcome measures
Measure	Effect of Short-term Rapamycin Treatment on Biomarker Ki67 n=12 Participants Biopsy samples from patients diagnosed with DCIS to determine the effect of short-term rapamycin treatment on biomarker Ki67	Treatment Group Adjacent breast tissues from the treatment group were tested for the effect of rapamycin treatment on the frequency of basal, luminal progenitor, and mature luminal epithelial cells.
The Effect of Short-term Rapamycin Treatment on Biomarker Ki67 Associated With Progression to Invasive Breast Cancer Pre-treatment	8.235 percentage of Ki67+ cells Standard Deviation 5.848	—
The Effect of Short-term Rapamycin Treatment on Biomarker Ki67 Associated With Progression to Invasive Breast Cancer Post-treatment	3.666 percentage of Ki67+ cells Standard Deviation 3.176	—

PRIMARY outcome

Timeframe: 5-7 day rapamycin treatment plus 3-7 day washout for the treatment group.

Population: We were only able to obtain fresh surgical tissues and mammary epithelial cell profiles by flowcytometry from 27 patients in the treatment group. The mean data of luminal progenitor cells were compared between the control and treatment groups with unpaired t test.

Assessment will be used to measure changes in luminal progenitor cell population between controls and treated patients.

Outcome measures

Outcome measures
Measure	Effect of Short-term Rapamycin Treatment on Biomarker Ki67 n=18 Participants Biopsy samples from patients diagnosed with DCIS to determine the effect of short-term rapamycin treatment on biomarker Ki67	Treatment Group n=27 Participants Adjacent breast tissues from the treatment group were tested for the effect of rapamycin treatment on the frequency of basal, luminal progenitor, and mature luminal epithelial cells.
The Effect of Short-term Rapamycin Treatment on the Frequency of Luminal Progenitor Epithelial Cells	11.82 percentage of total lineage neg. cells Standard Deviation 9.221	6.178 percentage of total lineage neg. cells Standard Deviation 5.525

PRIMARY outcome

Timeframe: 5-7 day rapamycin treatment plus 3-7 day washout for the treatment group.

Population: We were only able to obtain fresh surgical tissues and mammary epithelial cell profiles by flowcytometry from 27 patients in the treatment group. Out of the 27, only 22 samples yielded enough basal myoepithelial cells for the quantification of the SFE. Comparison between control group and treatment group.

Measurement of difference in sphere formation efficiency (SFE) by mammary stem cells (MaSCs) in the basal myoepithelial cell population between the control and treatment groups. SFE is an in vitro method by quantifying the number of spheres formed divided by the number of cells seeded. Higher SFE indicates higher frequency of MaSCs.

Outcome measures

Outcome measures
Measure	Effect of Short-term Rapamycin Treatment on Biomarker Ki67 n=18 Participants Biopsy samples from patients diagnosed with DCIS to determine the effect of short-term rapamycin treatment on biomarker Ki67	Treatment Group n=22 Participants Adjacent breast tissues from the treatment group were tested for the effect of rapamycin treatment on the frequency of basal, luminal progenitor, and mature luminal epithelial cells.
The Effect of Short-term Rapamycin Treatment on Sphere Formation Efficiency of Mammary Stem Cells	3.681 spheres formed per 1,000 cells Standard Deviation 2.303	0.717 spheres formed per 1,000 cells Standard Deviation 1.414

PRIMARY outcome

Timeframe: 5-7 day rapamycin treatment plus 3-7 day washout for the treatment group.

Population: We were only able to obtain fresh surgical tissues and mammary epithelial cell profiles by flowcytometry from 27 patients in the treatment group.

Measurement of Mature luminal cell populations in the treatment group compared to the control group.

Outcome measures

Outcome measures
Measure	Effect of Short-term Rapamycin Treatment on Biomarker Ki67 n=18 Participants Biopsy samples from patients diagnosed with DCIS to determine the effect of short-term rapamycin treatment on biomarker Ki67	Treatment Group n=27 Participants Adjacent breast tissues from the treatment group were tested for the effect of rapamycin treatment on the frequency of basal, luminal progenitor, and mature luminal epithelial cells.
The Effect of Short-term Rapamycin Treatment on the Frequency of Mature Luminal Epithelial Cells	11.82 percentage of total lineage neg. cells Standard Deviation 9.221	6.178 percentage of total lineage neg. cells Standard Deviation 5.525

PRIMARY outcome

Timeframe: 5-7 day rapamycin treatment plus 3-7 day washout for the treatment group.

The measurement of sphere formation efficiency (SFE) between luminal progenitor (LP) cells from the control group and those from the treatment group. SFE is an in vitro method by quantifying the number of spheres formed divided by the number of cells seeded. Higher SFE indicates higher frequency of LP cells.

Outcome measures

Outcome measures
Measure	Effect of Short-term Rapamycin Treatment on Biomarker Ki67 n=18 Participants Biopsy samples from patients diagnosed with DCIS to determine the effect of short-term rapamycin treatment on biomarker Ki67	Treatment Group n=22 Participants Adjacent breast tissues from the treatment group were tested for the effect of rapamycin treatment on the frequency of basal, luminal progenitor, and mature luminal epithelial cells.
The Effect of Short-term Rapamycin Treatment on Sphere Formation Efficiency of Luminal Progenitor Cells	20.82 Spheres formed from 1,000 cells Standard Deviation 20.97	30.32 Spheres formed from 1,000 cells Standard Deviation 34.15

Adverse Events

Rapamycin Treatment

Serious events: 0 serious events

Other events: 24 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Rapamycin Treatment n=40 participants at risk Adverse events are only reported for the treatment group who received the intervention.
General disorders Fatigue	7.5% 3/40 • 1 month It was used at a low dose and short term. Control group participants were not treated and therefore were not assessed for adverse events.
General disorders Headache	22.5% 9/40 • 1 month It was used at a low dose and short term. Control group participants were not treated and therefore were not assessed for adverse events.
General disorders Nausea	20.0% 8/40 • 1 month It was used at a low dose and short term. Control group participants were not treated and therefore were not assessed for adverse events.
Skin and subcutaneous tissue disorders Pruritus	5.0% 2/40 • 1 month It was used at a low dose and short term. Control group participants were not treated and therefore were not assessed for adverse events.
Skin and subcutaneous tissue disorders Rash	5.0% 2/40 • 1 month It was used at a low dose and short term. Control group participants were not treated and therefore were not assessed for adverse events.
Gastrointestinal disorders Stomach pain	7.5% 3/40 • 1 month It was used at a low dose and short term. Control group participants were not treated and therefore were not assessed for adverse events.
Gastrointestinal disorders Diarrhea	12.5% 5/40 • 1 month It was used at a low dose and short term. Control group participants were not treated and therefore were not assessed for adverse events.

Additional Information

LUZHE SUN, Ph.D.

University of Texas Health Science Center

Phone: 210-567-5746

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place