Abstract 1519: Estrogen receptor beta and p53 signaling crosstalk: implications for ER beta as a potential therapeutic target in triple negative breast cancer

Author(s):  
Christina E. Adams ◽  
Gokul M. Das
2020 ◽  
Vol 106 (1_suppl) ◽  
pp. 38-38
Author(s):  
HS Mubisi ◽  
MM Farouk ◽  
II Zaki ◽  
TA El Fayoiem ◽  
AA Ismail

Introduction: Triple negative breast cancer (TNBC), defined as lacking the expression of estrogen receptor alpha (ERα), progesterone receptor and human epidermal growth factor receptor is an aggressive breast cancer subtype for which there is a need to identify new therapeutic targets. About 50-80% of TNBC express Estrogen Receptor Beta (ERβ). Given its slight differences from ERα in terms of structure, signaling and its anti-proliferative effects on breast cancer cells, ERβ may be a possible therapeutic target. This study sought to assess the presence of ERβ and its correlation with the clinico-pathological features among the Egyptian females with TNBC. Material and Methods: The study was a retrospective analysis. The following data was retrieved from patient’s files and recorded: age, tumor size, lymph nodes metastasis, and stage. Paraffin blocks for patients confirmed by IHC to be TNBC were subjected to immunohistochemical staining for ERβ, CK5/6, and Ki 67. Results: ERβ was positive in 80% of cases (n=32/40). ERβ significantly correlated with Age (rs = -0.473, P = 0.002, n = 40), Tumor size (rs = -0.471, P = 0.007, n = 40), Lymph nodes (rs = -0.365, P = 0.021, n =40), and Stage (rs = -0.468, P = 0.002, n = 40). There was no correlation between ERβ with Ki-67 and CK5/6 a marker of the basal phenotype. All 8 patients without ERβ had an aggressive disease. 4 received neoadjuvant chemotherapy with minimum or no pathologic complete response in the axillary lymph nodes, 2 presented with upfront metastatic disease while the other 2 were cases of local recurrence with a change in the molecular phenotype of the tumor from luminal subtype to TNBC. Conclusion: This study shows ERβ expression occurs in TNBC. It may have the potential to become a therapeutic target for TNBC.


Cells ◽  
2020 ◽  
Vol 9 (4) ◽  
pp. 874 ◽  
Author(s):  
Elena Alexandrova ◽  
Jessica Lamberti ◽  
Pasquale Saggese ◽  
Giovanni Pecoraro ◽  
Domenico Memoli ◽  
...  

Triple-negative breast cancer (TNBC) is a highly heterogeneous disease, representing the most aggressive breast cancer (BC) subtype with limited treatment options due to a lack of estrogen receptor alpha (ERα), progesterone receptor (PR), and Erb-B2 receptor tyrosine kinase 2 (HER2/neu) expression. Estrogen receptor beta (ERβ) is present in a fraction of TNBC patients, where its expression correlates with improved patient outcomes, supported by the fact that it exerts oncosuppressive effects in TNBC cell models in vitro. ERβ is involved in microRNA-mediated regulation of gene expression in hormone-responsive BC cells and could mediate its actions through small noncoding RNAs (sncRNAs) in TNBCs also. To verify this possibility, smallRNA sequencing was performed on three ERβ-expressing cell lines from different TNBC molecular subtypes. Several sncRNAs resulted modulated by ERβ, with a subset being regulated in a tumor subtype-independent manner. Interestingly, sncRNA profiling of 12 ERβ+and 32 ERβ− primary TNBC biopsies identified 7 microRNAs, 1 PIWI-interacting RNA (piRNA), and 1 transfer RNA (tRNA) differentially expressed in ERβ+ compared to ERβ− tumors and cell lines. Among them, miR-181a-5p was found to be overexpressed in ERβ+ tumors and predicted target key components of the cholesterol biosynthesis pathway previously found to be inhibited by ERβ in TNBC cells.


Oncotarget ◽  
2018 ◽  
Vol 9 (74) ◽  
pp. 33912-33930 ◽  
Author(s):  
David Austin ◽  
Nalo Hamilton ◽  
Yahya Elshimali ◽  
Richard Pietras ◽  
Yanyuan Wu ◽  
...  

Author(s):  
Jharna Datta ◽  
Natalie Willingham ◽  
Jasmine Manouchehri ◽  
Joel David ◽  
Mirisha Sheth ◽  
...  

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