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

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.

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

10.21203/rs.2.23513/v1 ◽

2020 ◽

Author(s):

Toshiaki Iwase ◽

Kenichi Harano ◽

Hiroko Masuda ◽

Kumiko Kida ◽

Kenneth R. Hess ◽

...

Keyword(s):

Breast Cancer ◽

Gene Expression ◽

Inflammatory Breast Cancer ◽

Hormone Receptor ◽

Survival Outcome ◽

Stage Iii ◽

Prognostic Role ◽

Poor Survival ◽

Poor Survival Outcome

Abstract Purpose: 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 for 137 patients with HR+/HER2– IBC and 252 patients with corresponding 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 NAC 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: Increased HR positivity 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.

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The prognostic role of SPAG5 gene expression in breast cancer patients with systematic therapy

The Breast ◽

10.1016/s0960-9776(17)30347-8 ◽

2017 ◽

Vol 32 ◽

pp. S109-S110 ◽

Cited By ~ 1

Author(s):

C. Zhu ◽

X. Ma

Keyword(s):

Breast Cancer ◽

Gene Expression ◽

Cancer Patients ◽

Breast Cancer Patients ◽

Prognostic Role

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Increased expression of senescence markers p14ARFand p16INK4ain breast cancer is associated with an increased risk of disease recurrence and poor survival outcome

Histopathology ◽

10.1111/his.12948 ◽

2016 ◽

Vol 69 (3) ◽

pp. 479-491 ◽

Cited By ~ 10

Author(s):

Rahmawati Pare ◽

Joo-Shik Shin ◽

Cheok Soon Lee

Keyword(s):

Breast Cancer ◽

Disease Recurrence ◽

Survival Outcome ◽

Poor Survival ◽

Increased Risk ◽

Poor Survival Outcome ◽

Risk Of Disease

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

BMC Cancer ◽

10.1186/s12885-020-06940-z ◽

2020 ◽

Vol 20 (1) ◽

Author(s):

Toshiaki Iwase ◽

Kenichi Harano ◽

Hiroko Masuda ◽

Kumiko Kida ◽

Kenneth R. Hess ◽

...

Keyword(s):

Breast Cancer ◽

Gene Expression ◽

Expression Analysis ◽

Inflammatory Breast Cancer ◽

Hormone Receptor ◽

Gene Expression Analysis

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1917 Prognostic role of surrogate intrinsic subtypes in non-metastatic inflammatory breast cancer

European Journal of Cancer ◽

10.1016/s0959-8049(16)30866-8 ◽

2015 ◽

Vol 51 ◽

pp. S305

Author(s):

Z. Surmeli ◽

B. Cakar ◽

P. Gursoy ◽

B. Karabulut ◽

U.A. Sanli ◽

...

Keyword(s):

Breast Cancer ◽

Inflammatory Breast Cancer ◽

Prognostic Role ◽

Intrinsic Subtypes

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Independent validation of stromal uPA in archived tumor samples from the prospectively randomized ABCSG8 trial to provide level 1b evidence for a prognostic value of uPA immunohistochemistry in endocrine-treated postmenopausal breast cancer patients.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.15_suppl.536 ◽

2017 ◽

Vol 35 (15_suppl) ◽

pp. 536-536

Author(s):

Christian F. Singer ◽

Stephan W Jahn ◽

Margaretha Rudas ◽

Zsuzsanna Bago-Horvath ◽

Florian Fitzal ◽

...

Keyword(s):

Breast Cancer ◽

Cancer Patients ◽

Early Breast Cancer ◽

Hormone Receptor ◽

Prognostic Value ◽

Breast Cancer Patients ◽

Prognostic Role ◽

Hormone Receptor Positive ◽

Pai 1

536 Background: We have recently demonstrated that urokinase Plasminogen Activator (uPA), together with its inhibitor PAI-1, have prognostic value in hormone-receptor positive early breast cancer, and can be measured in FFPE archived tumor samples. We have now aimed to validate the prognostic role of uPA protein expression in FFPE archived tumor samples in an independent cohort of endocrine-treated breast cancer patients. Methods: 303 postmenopausal women with hormone receptor–positive, early breast cancer who had received 5 years of endocrine therapy in the prospectively designed ABCSG-08 trial, and in whom FFPE tumor tissue was available, were included in this analysis. Stromal uPA and PAI-1 protein expression was evaluated by immunohistochemistry and correlated with distant recurrence-free survival (DRFS) and overall survival (OS). Results: Stromal uPA was detected in 132 of 297 tumors (44.4%), and 74 out of 269 samples (27.5%) exhibited stromal PAI-1, while co-expression of both proteins was found in 48 of 294 (16.3%) samples. Neither uPA nor PAI-1 expression were associated with tumor size, age, nodal status, grading, or receptor status. Patients whose tumor stroma expressed uPA protein were more likely to have a shorter DRFS (adjusted HR for relapse: 2.78; 95% CI 1.31-5.93; p=0.008 Cox regression analysis) and OS (adjusted HR for death: 1.29; 95% CI 0.86-12.50; p=0.161) than women without uPA expression. No such association was observed for PAI-1 and for the uPA/PAI1 ratio. After a median follow-up of 5.6 years women with uPA-positive tumors experienced a significantly shorter DRFS (93.3% vs 84.8%; p<0.013 log rank test) and tended to have a worse OS (83.0.4% vs 77.3%; p=0.106) compared to women with uPA negative tumors. Conclusions: By confirming the clinical utility of stromal uPA IHC in archived breast cancer samples from an independent prospective randomized trial, we now provide level 1b evidence for a prognostic role of stromal uPA in women with endocrine-responsive early breast cancer.

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