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Title: Parity-related molecular signatures and breast cancer subtypes by estrogen receptor status.
Authors: Rotunno M,  Sun X,  Figueroa J,  Sherman ME,  Garcia-Closas M,  Meltzer P,  Williams T,  Schneider SS,  Jerry DJ,  Yang XR,  Troester MA
Journal: Breast Cancer Res
Date: 2014 Jul 8
Branches: GEB, HREB
PubMed ID: 25005139
PMC ID: not available
Abstract: INTRODUCTION: Relationships of parity with breast cancer risk are complex. Parity is associated with decreased risk of postmenopausal hormone receptor positive breast tumors, but may increase risk for basal-like breast cancers and for early onset tumors. Characterizing parity-related gene expression patterns in normal breast and breast tumor tissues may improve our understanding of the biological mechanisms underlying this complex pattern of risk. METHODS: We developed a parity signature by analyzing microRNA microarray data from 130 reduction mammoplasty (RM) subjects (54 nulliparous and 76 parous). This parity signature, together with published parity signatures, was evaluated in gene expression data from 150 paired tumors and adjacent benign breast tissues from the Polish Breast Cancer Study, overall and by tumor estrogen receptor (ER) status. RESULTS: We identified 251 genes significantly upregulated by parity status in RM patients (parous versus nulliparous, false discovery rate (FDR) = 0.008), including genes in immune, inflammation and wound response pathways. This parity signature was significantly enriched in normal and tumor tissues of parous breast cancer patients, specifically in ER-positive tumors. CONCLUSIONS: Our data corroborates epidemiologic data, suggesting that the etiology and pathogenesis of breast cancers vary by ER status, which may have implications for developing prevention strategies for these tumors.