Abstract 1680: Age-associated gene expression in normal breast tissue provide insights regarding associations between aging and aggressive tumor characteristics

Abstract

Abstract Age is the strongest breast cancer risk factor, with overall breast cancer risk increasing steadily beginning at approximately 30 years of age. Though several genomic studies have characterized differences in the biology of tumors arising in younger vs. older women, understanding of age-related gene expression in the non-malignant tissue is lacking. Because non-malignant tissue represents the microenvironment and/or field from which the tumor arises, an improved characterization of the age-related change in normal breast may provide suggestions of important pathways in the etiology of distinct breast cancer subtypes. To identify age-related changes in the breast microenvironment, 96 normal tissue specimens from reduction mammoplasty patients ranging in age from 14 to 70 were assayed by gene expression microarray. Significant associations between gene expression levels and age were identified for 802 genes (481 increased and 321 decreased with increasing age). Enriched functions included ‘aging of cells’, ‘shape change’, and ‘chemotaxis’, and enriched pathways included Wnt/beta-catenin signaling, Ephrin Receptor Signaling, Oncostatin M signaling, and JAK/Stat Signaling. Applying the age-associated genes to publicly available tumor datasets, the age-associated pathways defined two groups of tumors with distinct survival. The poor prognosis tumor group shared features of ‘younger’ breast tissue gene expression, providing a biological link to qualitative patterns in age at incidence. Aggressive tumors common in younger women (such as ER negative and basal-like breast cancers) harbor gene expression patterns that reflect the normal tissue from which they arise. For the young, these signatures portend more aggressive disease. These data show that studies of normal tissue gene expression can yield important insights about the pathways and biological selection factors that are relevant during tumor progression. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1680. doi:1538-7445.AM2012-1680