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

Abstract Background Poly (ADP-ribose)-polymerase inhibitors (PARPi) have been approved for cancer patients with germline BRCA1/2 (gBRCA1/2) mutations, and efforts to expand the utility of PARPi beyond BRCA1/2 are ongoing. In preclinical models of triple-negative breast cancer (TNBC) with intact DNA repair, we have previously shown an induced synthetic lethality with combined EGFR inhibition and PARPi. Here, we report the safety and clinical activity of lapatinib and veliparib in patients with metastatic TNBC. Methods A first-in-human, pilot study of lapatinib and veliparib was conducted in metastatic TNBC (NCT02158507). The primary endpoint was safety and tolerability. Secondary endpoints were objective response rates and pharmacokinetic evaluation. Gene expression analysis of pre-treatment tumor biopsies was performed. Key eligibility included TNBC patients with measurable disease and prior anthracycline-based and taxane chemotherapy. Patients with gBRCA1/2 mutations were excluded. Results Twenty patients were enrolled, of which 17 were evaluable for response. The median number of prior therapies in the metastatic setting was 1 (range 0–2). Fifty percent of patients were Caucasian, 45% African–American, and 5% Hispanic. Of evaluable patients, 4 demonstrated a partial response and 2 had stable disease. There were no dose-limiting toxicities. Most AEs were limited to grade 1 or 2 and no drug–drug interactions noted. Exploratory gene expression analysis suggested baseline DNA repair pathway score was lower and baseline immunogenicity was higher in the responders compared to non-responders. Conclusions Lapatinib plus veliparib therapy has a manageable safety profile and promising antitumor activity in advanced TNBC. Further investigation of dual therapy with EGFR inhibition and PARP inhibition is needed. Trial registration ClinicalTrials.gov, NCT02158507. Registered on 12 September 2014

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Gene expression analysis of invasive breast carcinoma yields differential patterns in luminal subtypes of breast cancer

Annals of Diagnostic Pathology ◽

10.1016/j.anndiagpath.2021.151814 ◽

2021 ◽

pp. 151814

Author(s):

Ahmed S. Abdelhafiz ◽

Merhan A. Fouda ◽

Nahla A. Elzefzafy ◽

Iman I. Taha ◽

Omar M. Mohemmed ◽

...

Keyword(s):

Breast Cancer ◽

Gene Expression ◽

Breast Carcinoma ◽

Expression Analysis ◽

Gene Expression Analysis ◽

Invasive Breast Carcinoma

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Gene expression analysis supports tumor threshold over 2.0 cm for T-category breast cancer

EURASIP Journal on Bioinformatics and Systems Biology ◽

10.1186/s13637-015-0034-5 ◽

2016 ◽

Vol 2016 (1) ◽

Cited By ~ 2

Author(s):

Hiroko K. Solvang ◽

Arnoldo Frigessi ◽

Fateme Kaveh ◽

Margit L. H. Riis ◽

Torben Lüders ◽

...

Keyword(s):

Breast Cancer ◽

Gene Expression ◽

Expression Analysis ◽

Gene Expression Analysis ◽

T Category

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Differential Gene Expression Analysis of Breast Cancer by Combining Sequence-Tagged Reverse-Transcription PCR with Pyrosequencing

Springer Protocols Handbooks - Advances and Clinical Practice in Pyrosequencing ◽

10.1007/978-1-4939-3308-2_31 ◽

2016 ◽

pp. 361-369

Author(s):

Xiaodan Zhang ◽

Haiping Wu ◽

Zhiyao Chen ◽

Bingjie Zou ◽

Qinxin Song ◽

...

Keyword(s):

Breast Cancer ◽

Gene Expression ◽

Differential Gene Expression ◽

Expression Analysis ◽

Reverse Transcription ◽

Gene Expression Analysis ◽

Differential Gene Expression Analysis ◽

Reverse Transcription Pcr ◽

Differential Gene

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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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