Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Breast Neoplasms

Breast Diseases

Skin Diseases

Anti-Infective Agents

Antineoplastic Agents

All Drugs and Chemicals

Sirolimus

Temsirolimus

MTOR Inhibitors

Anti-Bacterial Agents

Antibiotics, Antitubercular

Clotrimazole

Miconazole

Antifungal Agents

Immunosuppressive Agents

Immunologic Factors

Subjects will be 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 will be evaluated for lesion size, nuclear grade, presence of necrosis in each patient's core biopsy and surgical specimens, as well as IHC (ImmunoHistoChemistry) for biomarkers including p16, COX2 (cyclooxygenase-2), and Ki-67. Specimens will also be tested for rapamycin treatment on the properties of mammary stem/progenitor cells as another biomarker for gauging the efficacy of rapamycin treatment.

Low dose of rapamycin at 2 mg/day for -5-7 days of treatment

Rapamycin

LuZhe Sun, PhD

Ismail Jatoi, MD

To examine whether rapamycin can reduce malignant markers and aberrant mammary stem/progenitor cells (MaSCs) number in surgical specimens

A non-randomized, open-label, phase II, window of opportunity trial will be carried out to see if a 5-7 day rapamycin treatment can reduce malignant markers and aberrant MaSC number

Aging Mammary Stem Cells and Breast Cancer Prevention

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.

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

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.

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

National Cancer Institute (NCI)

LuZhe Sun

Co-Principal Investigator

It was used at a low dose and short term. Control group participants were not treated and therefore were not assessed for adverse events.

Adverse events are only reported for the treatment group who received the intervention.

Rapamycin Treatment

A total of 40 patients were consented to undergo treatment and 38 successfully completed the regiment.

Rapamycin Treatment Group

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

Un-treated Control Group

Total

Age, Categorical

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Region of Enrollment

This was a non-random, open-label, phase II, window of opportunity trial to investigate a possible inhibition of mammary stem cells (MaSCs) in non-cancerous tissue and/or malignant markers by rapamycin in patients with non-invasive breast cancer. A total of 40 patients agreed to undergo the treatment and 38 successfully completed the regiment. The control group for providing non-cancerous breast tissue included 12 patients with non-invasive breast cancer and 6 with invasive cancer.

Our hypothesis was that a low dose and short term treatment with rapamycin in patients with early stage breast cancer would show significantly attenuation of mammary stem and progenitor cell activity and tumor progression biomarkers in a non-randomized study.

LUZHE SUN, Ph.D.

Pre-treatment

Post-treatment

Biopsy samples from patients diagnosed with DCIS to determine the effect of short-term rapamycin treatment on biomarker Ki67

Effect of Short-term Rapamycin Treatment on Biomarker Ki67

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

The Effect of Short-term Rapamycin Treatment on Biomarker Ki67 Associated With Progression to Invasive Breast Cancer

Adjacent breast tissues from control group were used for measuring the frequency of basal, luminal progenitor, and mature luminal epithelial cells.

Control

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.

Treatment Group

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.

The Effect of Short-term Rapamycin Treatment on the Frequency of Luminal Progenitor Epithelial Cells

Adjacent breast tissues from control group were used for measuring the MaSC frequency in basal myoepithelial cells.

Adjacent breast tissues from the treatment group were used for measuring the MaSC frequency in basal myoepithelial cells.

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.

The Effect of Short-term Rapamycin Treatment on Sphere Formation Efficiency of Mammary Stem Cells

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

The Effect of Short-term Rapamycin Treatment on the Frequency of Mature Luminal Epithelial Cells

Adjacent breast tissues from control group were used for measuring the sphere formation efficiency of luminal progenitor cells.

Adjacent breast tissues from the treatment group were used for measuring the sphere formation efficiency of luminal progenitor cells.

The Effect of Short-term Rapamycin Treatment on Sphere Formation Efficiency of Luminal Progenitor Cells

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

Subjects that consented to provide tissue, but were not treated with Rapamycin

Spots Global Cancer Trial Database for Aging Mammary Stem Cells and Breast Cancer Prevention

Trial Identification

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Study Description

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