scholarly journals FOXP3 Transcription Factor: A Candidate Marker for Susceptibility and Prognosis in Triple Negative Breast Cancer

2014 ◽  
Vol 2014 ◽  
pp. 1-7 ◽  
Author(s):  
Leandra Fiori Lopes ◽  
Roberta Losi Guembarovski ◽  
Alda Losi Guembarovski ◽  
Marina Okuyama Kishima ◽  
Clodoaldo Zago Campos ◽  
...  

Triple negative breast cancer (TNBC) is a relevant subgroup of neoplasia which presents negative phenotype of estrogen and progesterone receptors and has no overexpression of the human epidermal growth factor 2 (HER2). FOXP3 (forkhead transcription factor 3) is a marker of regulatory T cells (Tregs), whose expression may be increased in tumor cells. This study aimed to investigate a polymorphism (rs3761548) and the protein expression of FOXP3 for a possible involvement in TNBC susceptibility and prognosis. Genetic polymorphism was evaluated in 50 patients and in 115 controls by allele-specific PCR (polymerase chain reaction). Protein expression was evaluated in 38 patients by immunohistochemistry. It was observed a positive association for homozygous AA (OR = 3.78; 95% CI = 1.02–14.06) in relation to TNBC susceptibility. Most of the patients (83%) showed a strong staining for FOXP3 protein in the tumor cells. In relation to FOXP3-positive infiltrate, 47% and 58% of patients had a moderate or intense intratumoral and peritumoral mononuclear infiltrate cells, respectively. Tumor size was positively correlated to intratumoral FOXP3-positive infiltrate (P=0.026). In conclusion, since FOXP3 was positively associated with TNBC susceptibility and prognosis, it seems to be a promising candidate for further investigation in larger TNBC samples.

2021 ◽  
Author(s):  
Shahan Mamoor

Women diagnosed with triple negative breast cancer can benefit neither from endocrine therapy nor from HER2-targeted therapies (1). We mined published microarray datasets (2, 3) to determine in an unbiased fashion and at the systems level genes most differentially expressed in the primary tumors of patients with breast cancer. We report here significant differential expression of the gene encoding E2F transcription factor 1, E2F1, when comparing the tumor cells of patients with triple negative breast cancer to normal mammary ductal cells (2). E2F1 was also differentially expressed in bulk tumor in human breast cancer (3). E2F1 mRNA was present at significantly increased quantities in TNBC tumor cells relative to normal mammary ductal cells. Analysis of human survival data revealed that expression of E2F1 in primary tumors of the breast was correlated with distant metastasis-free survival in patients with luminal A type cancer, while within triple negative breast cancer, primary tumor expression of E2F1 was correlated with recurrence-free survival in patients with mesenchymal stem-like subtype disease. E2F1 may be of relevance to initiation, maintenance or progression of triple negative breast cancers.


2021 ◽  
Author(s):  
Shahan Mamoor

Women diagnosed with triple negative breast cancer are predicted to benefit neither from endocrine therapy nor from HER2-targeted therapies (1). We mined published microarray datasets (2, 3) to determine in an unbiased fashion and at the systems level genes most differentially expressed in the primary tumors of patients with breast cancer. We report here significant differential expression of the gene encoding transcription factor Dp family member 3, TFDP3, when comparing the tumor cells of patients with triple negative breast cancer to normal mammary ductal cells (2). TFDP3 was also differentially expressed in the brain metastases of patients with brain metastatic breast cancer (3). TFDP3 mRNA was present at significantly increased quantities in TNBC tumor cells relative to normal mammary ductal cells. Analysis of human survival data revealed that expression of TFDP3 in primary tumors of the breast was correlated with distant metastasis-free survival in patients with basal-like and luminal B type cancer, while within triple negative breast cancer, primary tumor expression of TFDP3 was correlated with overall survival in patients with basal-like 1 subtype disease. TFDP3 may be of relevance to initiation, maintenance or progression of triple negative breast cancers.


2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Anna E. M. Bastiaansen ◽  
A. Mieke Timmermans ◽  
Marcel Smid ◽  
Carolien H. M. van Deurzen ◽  
Esther S. P. Hulsenboom ◽  
...  

AbstractNew therapies are an urgent medical need in all breast cancer subgroups. Metabotropic glutamate receptor 1 (mGluR1) is suggested as a potential new molecular target. We examined the prevalence mGluR1 expression in different clinically relevant breast cancer subgroups and determined its association with prognosis. In this retrospective cohort, 394 consecutive primary breast cancer tissues were incorporated into a tissue microarray and immunohistochemically stained for mGluR1. The prevalence of mGluR1 protein expression in different breast cancer subgroups was evaluated and correlated with metastasis-free survival (MFS) and overall survival (OS). In total, 56% (n = 219) breast cancer tissues had mGluR1 expression. In estrogen receptor (ER)-negative tumors, 31% (n = 18/58) had mGluR1 expression that was significantly associated with MFS (HR 5.00, 95% CI 1.03–24.35, p = 0.046) in multivariate analysis, independently from other prognostic factors. Of the 44 triple-negative breast cancer (TNBC), 25% (n = 11) expressed mGluR1. mGluR1 expression in TNBC was significantly associated with shorter MFS (HR 8.60, 95% CI 1.06–20.39, p = 0.044) and with poor OS (HR 16.07, 95% CI 1.16–223.10, p = 0.039). In conclusion, mGluR1 is frequently expressed in breast cancer. In ER-negative breast cancer and in TNBC mGluR1 protein expression is an unfavorable prognostic marker. This study provides rationale to explore mGluR1 as a novel target for breast cancer treatment, especially for the more aggressive TNBC.


2011 ◽  
Vol 2011 ◽  
pp. 1-13 ◽  
Author(s):  
Ayca Gucalp ◽  
Tiffany A. Traina

Triple-negative breast cancer (TNBC), a subtype distinguished by negative immunohistochemical assays for expression of the estrogen and progesterone receptors (ER/PR) and human epidermal growth factor receptor-2(HER2) represents 15% of all breast cancers. Patients with TNBC generally experience a more aggressive clinical course with increased risk of disease progression and poorer overall survival. Furthermore, this subtype accounts for a disproportionate number of disease-related mortality in part due to its aggressive natural history and our lack of effective targeted agents beyond conventional cytotoxic chemotherapy. In this paper, we will review the epidemiology, risk factors, prognosis, and the molecular and clinicopathologic features that distinguish TNBC from other subtypes of breast cancer. In addition, we will examine the available data for the use of cytotoxic chemotherapy in the treatment of TNBC in both the neoadjuvant and adjuvant setting and explore the ongoing development of newer targeted agents.


2021 ◽  
Author(s):  
Shahan Mamoor

Women diagnosed with triple negative breast cancer can benefit neither from endocrine therapy nor from HER2-targeted therapies (1). We mined published microarray datasets (2, 3) to determine in an unbiased fashion and at the systems level genes most differentially expressed in the primary tumors of patients with breast cancer. We report here significant differential expression of the gene encoding cyclin A2, CCNA2, when comparing the tumor cells of patients with triple negative breast cancer to normal mammary ductal cells (2). CCNA2 was also differentially expressed in bulk tumor in human breast cancer (3). CCNA2 mRNA was present at significantly increased quantities in TNBC tumor cells relative to normal mammary ductal cells. Analysis of human survival data revealed that expression of CCNA2 in primary tumors of the breast was correlated with overall survival in patients with basal-like type cancer, while within triple negative breast cancer, primary tumor expression of CCNA2 was correlated with overall survival in patients with basal-like 1, basal-like 2, and mesenchymal subtype disease. CCNA2 may be of relevance to initiation, maintenance or progression of triple negative breast cancers.


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