Epigenetic Testing for Breast Cancer Risk Stratification

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
University of Texas Southwestern Medical Center
ClinicalTrials.gov Identifier:
NCT01501656
First received: December 27, 2011
Last updated: September 17, 2014
Last verified: September 2014
  Purpose

Promoter region hypermethylation of tumor suppressor genes is one the earliest molecular events in malignant transformation and is readily detectable in apparently normal benign breast epithelium adjacent to breast cancers. The investigators hypothesize that DNA methylation of certain genes occurs as a field change in benign breast tissue that is at high risk for malignant transformation, and as such, can be exploited for tissue-based breast cancer risk stratification. Additional work is required to identify new DNA methylation markers potentially useful for periareolar fine needle aspiration (RP-FNA)-based breast cancer risk stratification, to determine whether these markers are methylated more frequently in benign samples from women who develop breast cancer, to determine whether assessment of these markers is reproducible, to determine whether tamoxifen reduces DNA methylation, and to better understand the pattern of DNA methylation in benign samples from unselected healthy control populations. Each of these objectives contributes to advancement of a clinically useful RP-FNA-based breast cancer risk stratification test.

In addition, identification of genes that are preferentially methylated in estrogen receptor (ER) negative breast cancer will provide clues to the underlying biology responsible for this aggressive form of breast cancer. This knowledge may lead to the discovery of the causes of ER negative breast cancer, approaches for recognizing women at increased risk for this type of breast cancer, and approaches for reducing this risk.

This study seeks to identify patterns of DNA methylation in benign breast epithelial cells associated with an increased risk for breast cancer with a focus on ER negative breast cancer.


Condition
Breast Cancer

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
Official Title: Epigenetic Testing for Breast Cancer Risk Stratification

Resource links provided by NLM:


Further study details as provided by University of Texas Southwestern Medical Center:

Primary Outcome Measures:
  • DNA methylation [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    This objective assesses methylation of seven genes in 97 archival breast cancer samples.


Secondary Outcome Measures:
  • Frequency of methylation [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    Measure the frequency of methylation of ER positive and ER negative breast cancer-associated genes in benign breast epithelial cells obtained by RP-FNA.


Biospecimen Retention:   Samples With DNA

benign samples from unselected healthy control populations


Estimated Enrollment: 429
Study Start Date: May 2012
Estimated Study Completion Date: December 2014
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Detailed Description:

Promoter region hypermethylation of tumor suppressor genes is one the earliest molecular events in malignant transformation and is readily detectable in apparently normal benign breast epithelium adjacent to breast cancers. We hypothesize that DNA methylation of certain genes occurs as a field change in benign breast tissue that is at high risk for malignant transformation, and as such, can be exploited for tissue-based breast cancer risk stratification. Additional work is required to identify new DNA methylation markers potentially useful for periareolar fine needle aspiration (RP-FNA)-based breast cancer risk stratification, to determine whether these markers are methylated more frequently in benign samples from women who develop breast cancer, to determine whether assessment of these markers is reproducible, to determine whether tamoxifen reduces DNA methylation, and to better understand the pattern of DNA methylation in benign samples from unselected healthy control populations. Each of these objectives contributes to advancement of a clinically useful RP-FNA-based breast cancer risk stratification test.

In addition, identification of genes that are preferentially methylated in estrogen receptor (ER) negative breast cancer will provide clues to the underlying biology responsible for this aggressive form of breast cancer. This knowledge may lead to the discovery of the causes of ER negative breast cancer, approaches for recognizing women at increased risk for this type of breast cancer, and approaches for reducing this risk.

  Eligibility

Ages Eligible for Study:   30 Years to 79 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population

Archived tumor tissue, Newly diagnosed primary breast cancer patients and healthy women who have never been diagnosed with breast cancer

Criteria

Inclusion Criteria:

  • Women between the ages of 30 and 79.
  • Untreated stage 1 - 3 invasive breast cancer or a woman never diagnosed with breast cancer.
  • BI-RADS 1, 2, or 3 breast imaging within 12 months for women >40 years of age recruited into the control group.

Exclusion Criteria:

  • <30 or >80 years of age
  • Unable to provide informed consent
  • Presence of an undefined palpable or mammographic breast lesion suspicious for malignancy (BIRADS 4 or 5)
  • Breast implants
  • Bilateral prophylactic mastectomy
  • Any prior breasts irradiation
  • Any systemic chemotherapy in the past
  • Performance status that restricted normal activity for a significant portion of the day
  • Use of luteinizing-hormone-releasing-hormone (LHRH) analogs, prolactin inhibitors, antiandrogens, or systemic glucocorticoids within three months
  • Ever use of tamoxifen, raloxifene, or other SERMs
  • Ever use of aromatase inhibitors
  • Pregnancy or lactation within six months
  • Bleeding diathesis of any kind

    1. Inherited coagulation disorder
    2. Current coumadin use
    3. Use of drugs that inhibit platelet aggregation within 10 days
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01501656

Locations
United States, Texas
UT Southwestern Medical Center
Dallas, Texas, United States, 75204
Sponsors and Collaborators
University of Texas Southwestern Medical Center
Investigators
Principal Investigator: Rolf Brekken, MD UT Southwetstern Medical Center
  More Information

No publications provided

Responsible Party: University of Texas Southwestern Medical Center
ClinicalTrials.gov Identifier: NCT01501656     History of Changes
Other Study ID Numbers: STU 092011-047, BC103910
Study First Received: December 27, 2011
Last Updated: September 17, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases

ClinicalTrials.gov processed this record on October 19, 2014