title: Different gene expressions are associated with the different molecular subtypes of inflammatory breast cancer.
abstract: The goal of this study was to determine whether gene expression differences exist between inflammatory breast cancers (IBC) and T stage-matched non-IBC patients stratified by hormone receptor and HER2 status. We used Affymetrix GeneChips to analyze 82 tumor samples (25 T4d patients, and 57 T4a-c patients) of newly diagnosed breast cancers. Genes that were differentially expressed between the IBC and non-IBC specimens were identified using the t test, and differential expression of gene sets was assessed using gene set analysis. Three distinct clinical subtypes of IBC and non-IBC were compared: ER-positive/HER2-normal, HER2-amplified, and ER-negative/HER2-normal. When we compared expression data from all IBC with all non-IBC, we found no significant differences after adjusting for multiple testing. When IBC and non-IBC tumors were compared by clinical subtype, however, significant differences emerged. Complement and immune system-related pathways were overexpressed in ER-positive/HER2-normal IBC. Protein translation and mTOR signaling were overexpressed in HER2-amplified IBC. Apoptosis-, neural-, and lipid metabolism-related pathways were overexpressed in ER-negative/HER2-normal IBC compared with non-IBC of the same receptor phenotype. In this T stage-matched case-control study, the survival curves of patients with IBC and non-IBC were similar for all three clinical subtypes. IBC tumors can be divided into molecular and clinical subtypes similar to those of non-IBC. Clinical subtypes of IBC show molecular differences compared with similar subtypes of non-IBC.
authors.affiliation: Breast Cancer Translational Research Laboratory, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Takayuki
authors.initials: T
authors.lastname: Iwamoto
authors.forename: Giampaolo
authors.initials: G
authors.lastname: Bianchini
authors.forename: Yuan
authors.initials: Y
authors.lastname: Qi
authors.forename: Massimo
authors.initials: M
authors.lastname: Cristofanilli
authors.forename: Anthony
authors.initials: A
authors.lastname: Lucci
authors.forename: Wendy A
authors.initials: WA
authors.lastname: Woodward
authors.forename: James M
authors.initials: JM
authors.lastname: Reuben
authors.forename: Junji
authors.initials: J
authors.lastname: Matsuoka
authors.forename: Yun
authors.initials: Y
authors.lastname: Gong
authors.forename: Savitri
authors.initials: S
authors.lastname: Krishnamurthy
authors.forename: Vicente
authors.initials: V
authors.lastname: Valero
authors.forename: Gabriel N
authors.initials: GN
authors.lastname: Hortobagyi
authors.forename: Fredika
authors.initials: F
authors.lastname: Robertson
authors.forename: W Fraser
authors.initials: WF
authors.lastname: Symmans
authors.forename: Lajos
authors.initials: L
authors.lastname: Pusztai
authors.forename: Naoto T
authors.initials: NT
authors.lastname: Ueno
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001706:Biopsy; D001943:Breast Neoplasms / Q000378:metabolism*; D015331:Cohort Studies; D047628:Estrogen Receptor alpha / Q000378:metabolism*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D058922:Inflammatory Breast Neoplasms / Q000175:diagnosis / Q000378:metabolism*; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D015398:Signal Transduction; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism
chemical_list: D047628:Estrogen Receptor alpha; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases