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

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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.

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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

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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).

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Authors and Affiliations

  1. Breast Cancer Translational Research Laboratory, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA

    Takayuki Iwamoto, Giampaolo Bianchini, Lajos Pusztai & Naoto T. Ueno

  2. Department of Breast Medical Oncology, Unit 1354, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX, 77030, USA

    Takayuki Iwamoto, Giampaolo Bianchini, Massimo Cristofanilli, Vicente Valero, Gabriel N. Hortobagyi, Lajos Pusztai & Naoto T. Ueno

  3. Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA

    Yuan Qi

  4. Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA

    Anthony Lucci

  5. Department of Radiation Oncology Treatment, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA

    Wendy A. Woodward

  6. Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA

    James M. Reuben

  7. Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA

    Yun Gong, Savitri Krishnamurthy & W. Fraser Symmans

  8. Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA

    Fredika Robertson

  9. Stem Cell Transplantation/Cellular Therapy Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA

    Naoto T. Ueno

  10. Department of Gastroenterological Surgery and Surgical Oncology, Okayama University, Okayama, Okayama, 700-8558, Japan

    Takayuki Iwamoto & Junji Matsuoka

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  1. Takayuki Iwamoto
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  2. Giampaolo Bianchini
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  3. Yuan Qi
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Corresponding authors

Correspondence to Lajos Pusztai or Naoto T. Ueno.

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Lajos Pusztai and Naoto T. Ueno have contributed equally to this work.

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Iwamoto, T., Bianchini, G., Qi, Y. et al. Different gene expressions are associated with the different molecular subtypes of inflammatory breast cancer. Breast Cancer Res Treat 125, 785–795 (2011). https://doi.org/10.1007/s10549-010-1280-6

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