Transformation Potential of E2 Exposed Breast Cancer Susceptibility Gene Mutation Heterozygous Epithelial Breast Cells

NCT01907438 | Unknown DMC

• 1 other identifier: ISF-1702/12
• Study Type: observational
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

Susceptibility to breast cancer is related to the combination of genetic, hormonal and multiple other environmental risk factors, such as mutations in the BRCA gene and excess exposure to exogenous estrogen, respectively. BRCA is a nuclear protein that maintains genome stability, by acting as a key player in the DNA repair complex. Recently, evidence has emerged that BRCA mutation heterozygosis itself enhances aborted DNA repair and can contribute to breast cancer initiation after exposure to irradiation. In our preliminary results on short-term lymphocyte cultures, we found additional evidence that healthy heterozygous BRCA1 and BRCA2 mutation carriers have a different response to DNA damage than do non-carriers. The main aim of our ongoing project is to identify the transcriptional modulation and transformation potential of normal BRCA1 and BRCA2 mutation heterozygous epithelial breast cells following irradiation and to examine how it is affected by exposure to estrogen. Our hypotheses will be investigated by RNA-seq and microRNA-seq in order to identify a unique molecular expression profile of the estrogen exposed cells following ionizing irradiation. Understanding the role of BRCA heterozygosity in cell response to exposure to estrogen and to irradiation may facilitate the development of more appropriate diagnostic and therapeutic strategies for these individuals.

Conditions

BRCA1 Gene Mutation; BRCA2 Gene Mutation

Keywords

BRCA; estrogen; epithelial breast cells; genome profile

Outcome Measures

Primary Outcomes (1)

• The transcriptional profile of heterozygous epithelial breast cells

  we will perform a RNA-seq expression profiling analysis of normal estrogen exposed BRCA heterozygous epithelial cells following irradiation.

  human breast tissue samples will be obtained from premenopausal women undergoing breast surgery. cells will be isolated immediatly and 48h later the transcriptional profile will be identified.

Study Arms (3)

non-carriers

Tissues from premenopausal women undergoing esthetic breast surgery with no family history of breast or ovarian cancers will be obtained.epithelial breast cells will be isolated, treated with estrogen for 48 h and then will be irradiated.

BRCA1 mutation carriers

Tissues from risk-reducing mastectomy in healthy premenopausal women with BRCA1 mutations undergoing.epithelial breast cells will be isolated, treated with estrogen for 48 h and then will be irradiated.

BRCA2 mutation carriers

Tissues from risk-reducing mastectomy in healthy premenopausal women with BRCA2 mutations undergoing.epithelial breast cells will be isolated, treated with estrogen for 48 h and then will be irradiated.

Eligibility Criteria

• Age: 25 Years - 50 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)
• Sampling Method: Non-Probability Sample

Study Population

human breast tissue samples will be obtained from risk-reducing mastectomy in healthy premenopausal women with BRCA1 and BRCA2 mutations. Tissues from premenopausal women undergoing esthetic breast surgery with no family history of breast or ovarian cancers also will be obtained.

You may qualify if:

• healthy
• premenopausal
• women
• BRCA1 mutations
• BRCA2 mutations

You may not qualify if:

• women with breast or ovarian cancer

Sponsors & Collaborators

• Hadassah Medical Organization: lead

Study Sites (1)

Hadassah medical center

Jerusalem, Israel

Location

Study Officials

• Asher Y Salmon, MD, PhD

  Hadassah Medical Organization

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Asher Y Salmon, MD, PhD

CONTACT

asalmon@hadassah.org.il

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: CROSS SECTIONAL
• Target Duration: 7 Days
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Asher Salmon

Study Record Dates

• First Submitted: July 22, 2013
• First Posted: July 25, 2013
• Study Start: September 1, 2013
• Primary Completion: September 1, 2014
• Study Completion: September 1, 2015
• Last Updated: July 25, 2013

Record last verified: 2013-07

Locations

IL (1)