Identification of distinct gene expression signatures in histologically normal epithelium from patients with different breast cancer risk

Genomic alterations exist before histological evidence of malignancy, yet cancer precursors are seriously understudied. Investigating these precursors would help elucidate the features of breast cancer initiation and progression. We hypothesized that the gene expression in histologically normal epithelium from breast cancer patients (HN) would differ from gene expression in histologically normal epithelium from reduction mammoplasty controls (RM). We found the gene expression profiles were different in the two tissues genes downregulated in HN include MAPK pathway components as well as transcription factors ( ATF3, ETS2, MAFF, and TXNIP).There are no studies of comprehensive gene expression in prophylactic mastectomy samples, although their clinical characteristics are well-studied. Knowledge of gene expression changes in these tissues could be integrated into existing risk-assessment models, improving their accuracy. We hypothesized gene expression in histologically normal epithelium of women at high breast cancer risk, undergoing prophylactic mastectomy (PM), would show greater similarity to HN samples than RM samples. We found the PM expression profile is more similar to HN samples than RM samples, with the exception of the genes in the MAPK pathway, which had a more similar expression signature to RMs than HNs.Breast cancer is a heterogeneous disease whose origin is unclear. Many studies have sought to define the transcriptome of tumors and classify them based on their gene expression. To date, few studies have focused on gene expression profiles in the histologically normal epithelium from women with breast cancer. Studying the earliest divergent features in ER+ and ER- breast cancer patients will help to develop more tailored therapies for specific types of the disease. We hypothesized there are differences in gene expression between histologically normal epithelium from ER+ and ER- breast cancer patients. We found that pathways implicated in ER+ carcinogenesis (the ESR and GATA3 Pathways) were present in histologically normal epithelium from ER+ patients, while immune response genes composed 32% of genes with a higher expression in histologically normal epithelium from ER- patients.The gene expression differences identified between the samples demonstrate identification of distinct early changes in breast carcinogenesis in specific patient populations. Identification of these early changes will help to accurately determine risk and develop more specific agents for breast cancer treatment and prevention.