Epigenetic Testing for Breast Cancer Risk Stratification
Condition: Breast Cancer
MeSH terms: Breast Neoplasms
Study type: Observational

Summary: 
      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.
    

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.
    

Observational model: Cohort
Time perspective: Prospective
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
      
Biospecimen description: 
      benign samples from unselected healthy control populations