title: High incidence of triple negative breast cancers following pregnancy and an associated gene expression signature.
abstract: Breast cancer risk increases transiently in the period following pregnancy; pregnancy-associated breast cancers (PABC) are more aggressive than cases diagnosed in nulliparous women. We have previously reported that in the normal human breast pregnancy results in the upregulation of a number of inflammation related genes, suggesting a pro-tumorigenic environment as well as downregulation of ESR1 (ERα) and ERBB2 (HER2) and upregulation of ESR2 (ERβ), suggesting a protective effect. In this study, we aimed to investigate the possibility of differential regulation of the same gene set modulated in the normal breast, in human breast tumors following pregnancy. Gene expression was measured by real-time PCR on tumor regions isolated by laser capture microdissection from paraffin sections. Immunohistochemistry was performed on tissue microarrays (TMA) for protein expression. Hierarchical clustering was performed using the average linkage method to determine coordinate expression of sets of genes. We find that breast cancers detected within 10 years following pregnancy display a different gene expression pattern than those detected in nulliparous breast cancer patients. The gene expression difference is mainly attributable to a triple negative (TNBC) subgroup found to be more frequent in PABCs up to 10 years following a pregnancy. We also show that protein and mRNA expression levels correlate in half of the proteins tested by TMA. Despite the fact that this is a small study of 53 patients, we identified a gene expression signature that is differentially expressed in pregnancy-associated TNBC.
authors.affiliation: Department of Biopharmaceutical Sciences, University of Illinois at Chicago, Chicago, IL USA.
authors.forename: Szilard
authors.initials: S
authors.lastname: Asztalos
authors.affiliation: Department of Biopharmaceutical Sciences, University of Illinois at Chicago, Chicago, IL USA.
authors.forename: Thao N
authors.initials: TN
authors.lastname: Pham
authors.affiliation: Department of Pathology, University of Illinois at Chicago, Chicago, IL USA.
authors.forename: Peter H
authors.initials: PH
authors.lastname: Gann
authors.affiliation: Department of Biopharmaceutical Sciences, University of Illinois at Chicago, Chicago, IL USA.
authors.forename: Meghan K
authors.initials: MK
authors.lastname: Hayes
authors.affiliation: Department of Pathology, University of Illinois at Chicago, Chicago, IL USA.
authors.forename: Ryan
authors.initials: R
authors.lastname: Deaton
authors.affiliation: Department of Pathology, University of Illinois at Chicago, Chicago, IL USA.
authors.forename: Elizabeth L
authors.initials: EL
authors.lastname: Wiley
authors.affiliation: Department of Pathology, University of Illinois at Chicago, Chicago, IL USA.
authors.forename: Rajyasree
authors.initials: R
authors.lastname: Emmadi
authors.affiliation: Department of Pathology, University of Illinois at Chicago, Chicago, IL USA.
authors.forename: Andre
authors.initials: A
authors.lastname: Kajdacsy-Balla
authors.affiliation: Allina Health, Minneapolis, MN USA.
authors.forename: Nilanjana
authors.initials: N
authors.lastname: Banerji
authors.affiliation: Allina Health, Minneapolis, MN USA.
authors.forename: William
authors.initials: W
authors.lastname: McDonald
authors.affiliation: Department of Surgery, Northwestern Feinberg School of Medicine, Chicago, IL USA.
authors.forename: Seema A
authors.initials: SA
authors.lastname: Khan
authors.affiliation: Department of Biopharmaceutical Sciences, University of Illinois at Chicago, Chicago, IL USA.
authors.forename: Debra A
authors.initials: DA
authors.lastname: Tonetti
keywords: Inflammation; Parity; Pregnancy-associated breast cancer; Triple negative breast cancer