Epigenetic Testing for Breast Cancer Risk Stratification

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.