Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2020 May 18;20(1):430.
doi: 10.1186/s12885-020-06940-z.

Quantitative hormone receptor (HR) expression and gene expression analysis in HR+ inflammatory breast cancer (IBC) vs non-IBC

Toshiaki Iwase  1   2 , Kenichi Harano  1   2 , Hiroko Masuda  1   2 , Kumiko Kida  1   2 , Kenneth R Hess  3 , Ying Wang  4 , Luc Dirix  5 , Steven J Van Laere  5 , Anthony Lucci  1   6 , Savitri Krishnamurthy  1   7 , Wendy A Woodward  1   8 , Rachel M Layman  1   9 , François Bertucci  10 , Naoto T Ueno  11   12
Affiliations

Quantitative hormone receptor (HR) expression and gene expression analysis in HR+ inflammatory breast cancer (IBC) vs non-IBC

Toshiaki Iwase et al. BMC Cancer. .

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.

Keywords: Estrogen receptors; Gene expression; Immunohistochemistry; Inflammatory breast neoplasms.

PubMed Disclaimer

Conflict of interest statement

The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Effects of change in ER% and PR% on survival outcomes by multivariate analysis. a Comparison of hazard ratio for distant disease-free survival according to the change in ER and PR expression. b Comparison of hazard ratio for overall survival according to the change in ER and PR expression
Fig. 2
Fig. 2
Survival outcomes according to newly defined cutoff points for ER and PR expression in ER+/HER2– IBC and corresponding non-IBC. a Distant disease-free survival by ER and PR levels for non-IBC. b Distant disease-free survival by ER and PR levels for IBC c Overall survival by ER and PR levels for non-IBC. d Overall survival by ER and PR levels for IBC
See this image and copyright information in PMC

References

    1. Hance KW, Anderson WF, Devesa SS, Young HA, Levine PH. Trends in inflammatory breast carcinoma incidence and survival: the surveillance, epidemiology, and end results program at the National Cancer Institute. J Natl Cancer Inst. 2005;97(13):966–975. doi: 10.1093/jnci/dji172. - DOI - PMC - PubMed
    1. Gonzalez-Angulo AM, Hennessy BT, Broglio K, Meric-Bernstam F, Cristofanilli M, Giordano SH, Buchholz TA, Sahin A, Singletary SE, Buzdar AU, Hortobagyi GN. Trends for inflammatory breast cancer: is survival improving? Oncologist. 2007;12(8):904–912. doi: 10.1634/theoncologist.12-8-904. - DOI - PubMed
    1. Stendahl M, Ryden L, Nordenskjold B, Jonsson PE, Landberg G, Jirstrom K. High progesterone receptor expression correlates to the effect of adjuvant tamoxifen in premenopausal breast cancer patients. Clinical cancer research : an official journal of the American Association for Cancer Research. 2006;12(15):4614–4618. doi: 10.1158/1078-0432.ccr-06-0248. - DOI - PubMed
    1. Liu J, Guo H, Mao K, Zhang K, Deng H, Liu Q. Impact of estrogen receptor-beta expression on breast cancer prognosis: a meta-analysis. Breast Cancer Res Treat. 2016;156(1):149–162. doi: 10.1007/s10549-016-3721-3. - DOI - PubMed
    1. Ma H, Lu Y, Marchbanks PA, Folger SG, Strom BL, McDonald JA, Simon MS, Weiss LK, Malone KE, Burkman RT, Sullivan-Halley J, Deapen DM, Press MF, Bernstein L. Quantitative measures of estrogen receptor expression in relation to breast cancer-specific mortality risk among white women and black women. BCR. 2013;15(5):R90. doi: 10.1186/bcr3486. - DOI - PMC - PubMed

MeSH terms