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Breast Cancer Research and Treatment

, Volume 125, Issue 3, pp 785–795 | Cite as

Different gene expressions are associated with the different molecular subtypes of inflammatory breast cancer

  • Takayuki Iwamoto
  • Giampaolo Bianchini
  • Yuan Qi
  • Massimo Cristofanilli
  • Anthony Lucci
  • Wendy A. Woodward
  • James M. Reuben
  • Junji Matsuoka
  • Yun Gong
  • Savitri Krishnamurthy
  • Vicente Valero
  • Gabriel N. Hortobagyi
  • Fredika Robertson
  • W. Fraser Symmans
  • Lajos PusztaiEmail author
  • Naoto T. UenoEmail author
Clinical trial

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.

Keywords

Inflammatory breast cancer Receptor subtypes cDNA microarray Gene set analysis 

Abbreviations

IBC

Inflammatory breast cancers

FNA

Fine needle aspiration

GEO

Gene expression omnibus

ER

Estrogen receptor

HER2

Human epidermal growth factor Receptor 2

FDR

False discovery rates

SAM

Significance analysis of microarrays

IPA

Ingenuity pathway analysis software

GSA

Gene set analysis

RT-PCR

Reverse transcription polymerase chain reaction

mTOR

Mammalian target of rapamycin

Notes

Acknowledgments

This work was supported by the followings: the Breast Cancer Research Foundation (LP and WFS), MD Anderson Cancer Center Faculty Incentive Funds (WFS), the Commonwealth Cancer Foundation (LP and WFS) and MD Anderson’s Cancer Center Support Grant (CA016672) (NTU), the National Institute of Health R01CA138239-01 (WAW), The State of Texas Grant for Rare and Aggressive Cancers(MC and WAW), the American Airlines Komen Foundation Promise Grant KGO81287(WAW), and Morgan Welch Inflammatory Breast Cancer Research Program (MCNTU).

Supplementary material

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Supplementary material 1 (XLS 54 kb)
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Supplementary material 6 (docx 18 kb)

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Copyright information

© Springer Science+Business Media, LLC. 2010

Authors and Affiliations

  • Takayuki Iwamoto
    • 1
    • 2
    • 10
  • Giampaolo Bianchini
    • 1
    • 2
  • Yuan Qi
    • 3
  • Massimo Cristofanilli
    • 2
  • Anthony Lucci
    • 4
  • Wendy A. Woodward
    • 5
  • James M. Reuben
    • 6
  • Junji Matsuoka
    • 10
  • Yun Gong
    • 7
  • Savitri Krishnamurthy
    • 7
  • Vicente Valero
    • 2
  • Gabriel N. Hortobagyi
    • 2
  • Fredika Robertson
    • 8
  • W. Fraser Symmans
    • 7
  • Lajos Pusztai
    • 1
    • 2
    Email author
  • Naoto T. Ueno
    • 1
    • 2
    • 9
    Email author
  1. 1.Breast Cancer Translational Research LaboratoryThe University of Texas MD Anderson Cancer CenterHoustonUSA
  2. 2.Department of Breast Medical Oncology, Unit 1354The University of Texas MD Anderson Cancer CenterHoustonUSA
  3. 3.Department of Bioinformatics and Computational BiologyThe University of Texas MD Anderson Cancer CenterHoustonUSA
  4. 4.Department of Surgical OncologyThe University of Texas MD Anderson Cancer CenterHoustonUSA
  5. 5.Department of Radiation Oncology TreatmentThe University of Texas MD Anderson Cancer CenterHoustonUSA
  6. 6.Department of HematopathologyThe University of Texas MD Anderson Cancer CenterHoustonUSA
  7. 7.Department of PathologyThe University of Texas MD Anderson Cancer CenterHoustonUSA
  8. 8.Department of Experimental TherapeuticsThe University of Texas MD Anderson Cancer CenterHoustonUSA
  9. 9.Stem Cell Transplantation/Cellular Therapy OncologyThe University of Texas MD Anderson Cancer CenterHoustonUSA
  10. 10.Department of Gastroenterological Surgery and Surgical OncologyOkayama UniversityOkayamaJapan

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