scholarly journals Management Options in Triple-Negative Breast Cancer

2011 ◽  
Vol 5 ◽  
pp. BCBCR.S6562 ◽  
Author(s):  
Christina A. Minami ◽  
Debra U. Chung ◽  
Helena R. Chang
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Poor Prognosis ◽  
Triple Negative ◽  
Brca1 Mutation ◽  
Chemotherapeutic Agents ◽  
Disease Entity ◽  
Management Options ◽  
Biological Specificity ◽  
Broad Overview

Notorious for its poor prognosis and aggressive nature, triple-negative breast cancer (TNBC) is a heterogeneous disease entity. The nature of its biological specificity, which is similar to basal-like cancers, tumors arising in BRCA1 mutation carriers, and claudin-low cancers, is currently being explored in hopes of finding the targets for novel biologics and chemotherapeutic agents. In this review, we aim to give a broad overview of the disease's nomenclature and epidemiology, as well as the basic mechanisms of emerging targeted therapies and their performance in clinical trials to date.

Current Update on Natural Agents Against Triple Negative Breast Cancer

2020 ◽  
pp. 91-113
Author(s):  
Prathibha Sivaprakasam ◽  
Sureshkumar Anandasadagopan ◽  
Tamilselvi Alagumuthu ◽  
Ashok Kumar Pandurangan
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Poor Prognosis ◽  
Triple Negative ◽  
Notch Pathway ◽  
Chemotherapeutic Agents ◽  
Current Evidence ◽  
Research Needs ◽  
Disease Entity ◽  
Natural Agents

Breast cancer (BC) is sub-categorized into several well-recognized subtypes including estrogen receptor (ER), progesterone receptor (PR), and HER2 triple-negative breast cancer (TNBC). It is a heterogeneous disease entity constituting about 15% of breast cancer cases worldwide. TNBC is associated with poor prognosis and lack of sustained response to conventional chemotherapeutic agents. Although no approved targeted therapy is available for TNBCs, molecular-profiling efforts have revealed promising molecular targets such as the Wnt/β-catenin, STAT3, VEGF, EGFR, polyadenosine ribose polymerase inhibitors (PARPi) and DNA repair pathway, androgen pathway, and NOTCH pathway. Moreover, more research needs to be performed in the area of TNBC aiming at dissecting potential pathways and identifying potential molecular signatures to develop new targeted biologic modifiers. Natural agents are the abundant chemical compounds available from diverse plants. The authors aimed to summarize the current evidence and discuss the natural agents that target TNBC using different pathways.

The clinical impact of the expression of the cancer stem cell marker CD44v9 in early triple negative breast cancer (TNBC).

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e12566-e12566
Author(s):  
Eriko Tokunaga ◽  
Wakako Tajiri ◽  
Katsumi Takizawa ◽  
Hideki Ijichi ◽  
Hiroki Ueo ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Poor Prognosis ◽  
Triple Negative ◽  
Chemotherapeutic Agents ◽  
Clinical Impact ◽  
High Expression ◽  
Stem Cell Marker ◽  
Low Grade ◽  
The Poor

e12566 Background: The adhesion molecule CD44 is expressed in cancer stem-like cells (CSCs). CD44 variant 9 (CD44v9), a splicing variant of CD44, has emerged as a novel marker of cancer stemness. CD44v9 was reported to be associated with the resistance to chemotherapy in several malignancies. We recently reported that the high expression of CD44v9 is associated with the poor prognosis of the patients with triple negative breast cancer (TNBC), who received neoadjuvant chemotherapy (NAC). In this study, we investigated the clinical impact of the expression of CD44v9 in early TNBC who underwent surgery without NAC. Methods: Among 2257 primary breast cancer patients at clinical stage I-III who underwent surgery without NAC form 2002 to 2015, 201 patients with TNBC were included in this study. The expression of CD44v9 was analyzed immunohistochemistry (IHC). The associations between the CD44v9 expression and the clinicopathological characteristics and the prognosis were investigated. The tumors with the positive staining in more than two third of the cancer cells were regarded to be high expression of CD44v9. Results: CD44v9 high expression was observed in 62 cases (30.8%) and the low expression was in 139 cases (69.2%). Many of the CD44v9 high tumors were low grade than the tumors with low CD44v9. There were no significant associations between the expression levels of CD44v9 and the tumor size, lymph node metastasis and the pathological stage (pStage). There were no differences in the prognosis between the high and low CD44v9 expression in pStage I. However, in the patients with the tumors with pT1c or more (pT2, pT3) and the patients with pStage 2 and more, the high CD44v9 expression was significantly associated with the poor prognosis in terms of distant recurrence-free survival (DRFS) and overall survival (OS). In addition, high CD44v9 was associated with significantly shorter survival after recurrence. Many of these patients received various chemotherapy in the adjuvant setting and after recurrence. Therefore, CD44v9 high expression is considered to be associated with the poor prognosis due to the resistance to various chemotherapeutic agents. Conclusions: The prognosis of the TNBC patients with the high expression of CD44v9 is poor, which might be induced by the resistance to various chemotherapeutic agents. These results suggest that CD44v9 might be a novel therapeutic target for TNBC.

scholarly journals PSMB5 is associated with proliferation and drug resistance in triple-negative breast cancer

2017 ◽  
Vol 33 (1) ◽  
pp. 102-108 ◽  
Author(s):  
Wensong Wei ◽  
Yufeng Zou ◽  
Qihua Jiang ◽  
Zhibin Zhou ◽  
Haolong Ding ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Poor Prognosis ◽  
Triple Negative ◽  
Functional Module ◽  
Enrichment Analysis ◽  
Chemotherapeutic Agents ◽  
Gene Set Enrichment Analysis ◽  
Disease Stage ◽  
Cancer Subtypes

Background: Triple-negative breast cancer (TNBC) is the most aggressive subtype of breast cancer, characterized by advanced disease stage and poor prognosis. Moreover, due to the lack of therapeutic markers, TNBC patients can’t benefit fully from currently available targeted therapies. Methods: To fully understand the molecular basis of TNBC, we used gene set enrichment analysis (GSEA) to screen out the most altered functional module in TNBC, from publicly available microarray data and studied the association of the candidate gene with TNBC development. Results: We found that the proteasome was significantly activated in TNBC. As compared with other breast cancer subtypes and normal tissue, proteasome subunit beta 5 (PSMB5), the key regulator of proteasome function, was overexpressed in TNBC tissue and predictive of poor prognosis. Moreover, we also found that PSMB5 knockdown induced TNBC apoptosis and significantly enhanced cancer cell sensitivity to the chemotherapeutic agents bortezomib and paclitaxel. Conclusions: Our results suggest a potential role for PSMB5 as a biomarker and therapeutic target for TNBC.

Loss of PTEN expression is associated with aggressive behavior and poor prognosis in Middle Eastern triple-negative breast cancer

2015 ◽  
Vol 151 (3) ◽  
pp. 541-553 ◽  
Author(s):  
Shaham Beg ◽  
Abdul K. Siraj ◽  
Sarita Prabhakaran ◽  
Zeenath Jehan ◽  
Dahish Ajarim ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Aggressive Behavior ◽  
Triple Negative Breast Cancer ◽  
Poor Prognosis ◽  
Triple Negative ◽  
Middle Eastern ◽  
Pten Expression

scholarly journals Low KIBRA Expression Is Associated with Poor Prognosis in Patients with Triple-Negative Breast Cancer

Medicina ◽  
2021 ◽  
Vol 57 (8) ◽  
pp. 837
Author(s):  
So-Woon Kim ◽  
Jinah Chu ◽  
Sung-Im Do ◽  
Kiyong Na
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Poor Prognosis ◽  
Triple Negative ◽  
Histological Grade ◽  
Growth Factor Receptor ◽  
Hippo Signaling ◽  
Luminal A ◽  
Luminal B ◽  
Epidermal Growth

Background and Objectives: Kidney and brain protein (KIBRA) is a protein encoded by the WW and C2 domain containing 1 (WWC1) gene and is involved in the Hippo signaling pathway. Recent studies have revealed the prognostic value of KIBRA expression; however, its role in breast cancer remains unclear. The aim of this study was to examine KIBRA expression in relation to the clinical and pathological characteristics of patients with breast cancer and to disease outcomes. Materials and Methods: We analyzed the expression of KIBRA and its correlation with event-free survival (EFS) outcomes in resected samples from 486 patients with breast cancer. Results: KIBRA expression was significantly different among the molecular subgroups (low KIBRA expression: luminal A, 46.7% versus 50.0%, p = 0.641; luminal B, 32.7% versus 71.7%, p < 0.001; human epidermal growth factor receptor 2 (HER2)-enriched, 64.9% versus 45.5%. p = 0.001; triple-negative, 73.6% versus 43.8%, p < 0.001). Low KIBRA expression was also associated with high nuclear grade (60.4% versus 37.8%, p < 0.001), high histologic grade (58.7% versus 37.0%, p < 0.001), and estrogen receptor (ER) negativity (54.2% versus 23.6%, p < 0.001). Low KIBRA expression was significantly associated with poor EFS (p = 0.041; hazard ratio (HR) 1.658; 95% confidence interval (CI), 1.015–2.709). Low KIBRA expression was an independent indicator of poor prognosis (p = 0.001; HR = 3.952; 95% CI = 1.542–10.133) in triple-negative breast cancer (TNBC). Conclusion: Low KIBRA expression was associated with higher histological grade, ER negativity and poor EFS of breast cancer. In particular, our data highlight KIBRA expression status as a potential prognostic marker for TNBC.

Expression of synuclein gamma indicates poor prognosis of triple-negative breast cancer

2013 ◽  
Vol 30 (3) ◽  
Author(s):  
Kejin Wu ◽  
Shuo Huang ◽  
Mingjie Zhu ◽  
Yunshu Lu ◽  
Jian Chen ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Poor Prognosis ◽  
Triple Negative ◽  
Synuclein Gamma

scholarly journals The Interaction of PI3K Inhibition with Homologous Recombination Repair in Triple Negative Breast Cancer Cells

2019 ◽  
Vol 22 ◽  
pp. 599-611
Author(s):  
Gamze Guney Eskiler
Keyword(s):  
Breast Cancer ◽  
Homologous Recombination ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Apoptotic Cell ◽  
Human Cancer ◽  
Brca1 Mutation ◽  
Annexin V ◽  
Pi3k Inhibition ◽  
Recombination Repair

Purpose: Aberrant activation of the phosphatidylinositol 3'-kinase (PI3K)-Akt signaling pathway is observed in many types of human cancer including triple negative breast cancer (TNBC). Additionally, dysregulation in the homologous recombination (HR)-dependent DNA-repair is associated with TNBC phenotype due to BRCA1/2 mutations or HR deficiency. Therefore, the hypothesis of this study was to evaluate the association of PI3K inhibition with HR pathway in TNBC in terms of BRCA1 mutation status. Methods: To examine the potential therapeutic effect of LY294002, an inhibitor of PI3K, on TNBC cell lines with known BRCA1 status, WST-1, annexin V, cell cycle analysis and AO/EB staining were performed. Additionally, RT-PCR and immunofluorescence analysis was used to explore the interaction between the inhibition of PI3K and HR functionality. Results: The findings showed that LY294002 could significantly inhibited the proliferation of TNBC cells. Furthermore, the suppression of PI3K resulted in HR impairment by BRCA1 and RAD51 downregulation and apoptotic cell death by the induction of DNA damage and BAX overexpression. Therefore, LY294002 was more effective in BRCA1-deficient TNBC cells. Conclusions: Consequently, targeted therapies based on the interaction of PI3K inhibition with BRCA1 mutations or HR deficiency in TNBC may be a promising strategy for the treatment of patients with TNBC.

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