Quantitative hormone receptor (HR) expression and gene expression analysis in HR+ inflammatory breast cancer (IBC) vs non-IBC
Toshiaki Iwase,
Kenichi Harano,
Hiroko Masuda,
Kumiko Kida,
Kenneth R. Hess,
Ying Wang,
Luc Dirix,
Steven J. Van Laere,
Anthony Lucci,
Savitri Krishnamurthy,
Wendy A. Woodward,
Rachel M. Layman,
François Bertucci,
Naoto T. Ueno
Affiliations
Toshiaki Iwase
Morgan Welch Inflammatory Breast Cancer Research Program and Clinic, The University of Texas MD Anderson Cancer Center
Kenichi Harano
Morgan Welch Inflammatory Breast Cancer Research Program and Clinic, The University of Texas MD Anderson Cancer Center
Hiroko Masuda
Morgan Welch Inflammatory Breast Cancer Research Program and Clinic, The University of Texas MD Anderson Cancer Center
Kumiko Kida
Morgan Welch Inflammatory Breast Cancer Research Program and Clinic, The University of Texas MD Anderson Cancer Center
Kenneth R. Hess
Department of Biostatistics, The University of Texas MD Anderson Cancer Center
Ying Wang
Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center
Luc Dirix
Department of Oncology, University of Antwerp
Steven J. Van Laere
Department of Oncology, University of Antwerp
Anthony Lucci
Morgan Welch Inflammatory Breast Cancer Research Program and Clinic, The University of Texas MD Anderson Cancer Center
Savitri Krishnamurthy
Morgan Welch Inflammatory Breast Cancer Research Program and Clinic, The University of Texas MD Anderson Cancer Center
Wendy A. Woodward
Morgan Welch Inflammatory Breast Cancer Research Program and Clinic, The University of Texas MD Anderson Cancer Center
Rachel M. Layman
Morgan Welch Inflammatory Breast Cancer Research Program and Clinic, The University of Texas MD Anderson Cancer Center
François Bertucci
Laboratory of Predictive Oncology, Centre de Recherche en Cancérologie de Marseille (CRCM), Inserm, U1068, CNRS UMR7258, Institut Paoli-Calmettes, Aix-Marseille Université
Naoto T. Ueno
Morgan Welch Inflammatory Breast Cancer Research Program and Clinic, The University of Texas MD Anderson Cancer Center
Abstract Background The purpose of this study was to determine the prognostic role of hormone receptor (HR) on inflammatory breast cancer (IBC) to elucidate its aggressive biological behavior. Methods We evaluated the expression of estrogen receptor (ER) and progesterone receptor (PR) by immunohistochemical staining and determined the predictive and prognostic role of HR expression on 189 patients with HR+/HER2– IBC and 677 patients with HR+/HER2– stage III non-IBC. Furthermore, we performed gene expression (GE) analyses on 137 patients with HR+/HER2– IBC and 252 patients with HR+/HER2– non-IBC to detect genes that are specifically overexpressed in IBC. Results The expression of ER% was significantly associated with longer distant disease-free survival and overall survival. However, there was no significant relationship between ER% and neoadjuvant chemotherapy outcome. In the GE study, 84 genes were identified as significantly distinguishing HR+ IBC from non-IBC. Among the top 15 canonical pathways expressed in IBC, the ERK/MAPK, PDGF, insulin receptor, and IL-7 signaling pathways were associated with the ER signaling pathway. Upregulation of the MYC gene was observed in three of these four pathways. Furthermore, HR+/HER2– IBC had significantly higher MYC amplification, and the genetic alteration was associated with poor survival outcome. Conclusions Higher ER expression was significantly associated with improved survival in both HR+/HER2– IBC and HR+/HER2– stage III non-IBC patients. HR+/HER2– IBC had several activated pathways with MYC upregulation, and the genetic alteration was associated with poor survival outcome. The results indicate that MYC may be a key gene for understanding the biology of HR+/HER2– IBC.
