scholarly journals PTPRT Could Be a Treatment Predictive and Prognostic Biomarker for Breast Cancer

2021 ◽  
Vol 2021 ◽  
pp. 1-23
Author(s):  
Lun Li ◽  
Feng Xu ◽  
Pingfang Xie ◽  
Liqin Yuan ◽  
Meirong Zhou
Keyword(s):  
Breast Cancer ◽  
Cell Cycle ◽  
Acquired Resistance ◽  
Age Groups ◽  
Breast Cancer Patients ◽  
Clinical Role ◽  
Primary Resistance ◽  
Free Survival ◽  
Predictive And Prognostic Biomarker

The role of PTPRT in breast cancer was not comprehensively explored and well analyzed. Our study comprehensively searched available databases to analyze the clinical role of PTPRT in breast cancer. We found PTPRT was an antioncogene and could be used to distinguish different stages, age groups, molecular types, and grades for breast cancer. PTPRT might be primary resistance biomarkers for taxane, anthracycline, and ixabepilone but not be acquired resistance biomarkers. Higher PTPRT expression levels were associated with longer overall survival and recurrence-free survival. PTPRT was negatively associated with Ki67 and CDK4/6 but positively associated with BCL-2. PTPRT might be associated with cell cycle and microtubule, and tumor infiltration in B cell and macrophage cell. PTPRT could predict chemotherapy effectiveness and prognosis for breast cancer patients. PTPRT might inhibit tumor growth via disrupting the microtubule dynamics and cell cycle in breast cancer.

scholarly journals Potential prognostic value of PD-L1 and FOXP3 as predictors of relapse in breast cancer

2019 ◽  
Vol 9 (2) ◽  
pp. 38
Author(s):  
Reham Nagib ◽  
Sherine Refat ◽  
Ahmed E. Eladl ◽  
Ziad Emarah ◽  
Khaled Elnaghi
Keyword(s):  
Breast Cancer ◽  
Disease Free Survival ◽  
Treg Cells ◽  
Clinicopathological Parameters ◽  
Advanced Stage ◽  
Breast Cancer Patients ◽  
Duct Carcinoma ◽  
Free Survival ◽  
Cancer Management

Background: Expression of PD-L1 detected by immunohistochemistry can represent a new hope for cancer management. The role of PD L1 in breast cancer is still unclear. Similarly, is the role of tumor-infiltrating FOXP3 +ve regulatory T (Treg) cells where literature data are conflicting. Our study aimed to evaluate the immunohistochemical expression of PD L1 and FOXP3 in breast cancer, correlate them with clinicopathological parameters as well as evaluating their relation.Methods: This is a retrospective study carried out on 136 breast cancer specimens. Only cases with proved pathological diagnosis of infiltrating duct carcinoma of no special type (NST) were included. Tissue microarray blocks were constructed and immunostained with the polyclonal antibody for PDL1 and monoclonal antibody for FOXP3.Results: Statistically significant correlation was found between high FOXP3 and nearly all adverse prognostic factors including; grade III tumors (p = .003), basal-like subtype(p = .001), high Ki67(p = .001), negative ER status(p = .001), negative PR(p = .028), HER2 expression(p = .04), advanced stage (p = .001), and LN metastases(p = .001). For PDL1, only statistically significant correlation with high Ki67 (p = .018) and advanced stage(p = .03) was found. A statistically significant positive correlation was found between PD L1 and FOXP3(p= .001). No statistically significant correlation was found between both PDL1 and FOXP3 in relation to disease-free survival (DFS) (p = .054). PDL1, age (≥ 50 years), nodal metastases were significant predictors of relapse in breast cancer.Conclusion: The current study supports PDL1 as a predictor of relapse in breast cancer. Additionally, it highlights the synergistic role between PDL1 and FOXP3 in breast cancer microenvironment. Each can be considered as a poor prognostic marker in breast cancer. This raises a concern about the benefit of breast cancer patients from blocking of PDL1 pathway.

scholarly journals Roles for miRNAs in endocrine resistance in breast cancer

2015 ◽  
Vol 22 (5) ◽  
pp. R279-R300 ◽  
Author(s):  
Penn Muluhngwi ◽  
Carolyn M Klinge
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Aromatase Inhibitors ◽  
Estrogen Receptor Alpha ◽  
Acquired Resistance ◽  
Endocrine Resistance ◽  
Breast Cancer Patients ◽  
Initial Tumor ◽  
Bona Fide

Therapies targeting estrogen receptor alpha (ERα), including selective ER modulators such as tamoxifen, selective ER downregulators such as fulvestrant (ICI 182 780), and aromatase inhibitors such as letrozole, are successfully used in treating breast cancer patients whose initial tumor expresses ERα. Unfortunately, the effectiveness of endocrine therapies is limited by acquired resistance. The role of microRNAs (miRNAs) in the progression of endocrine-resistant breast cancer is of keen interest in developing biomarkers and therapies to counter metastatic disease. This review focuses on miRNAs implicated as disruptors of antiestrogen therapies, theirbona fidegene targets and associated pathways promoting endocrine resistance.

Immunologic markers associated with favorable prognosis in breast cancer patients: Role of innate immune system.

2011 ◽  
Vol 29 (27_suppl) ◽  
pp. 43-43
Author(s):  
M. L. Ascierto ◽  
M. Kmieciak ◽  
M. O. Idowu ◽  
D. Bedognetti ◽  
A. De Maria ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Nk Cells ◽  
Nk Cell ◽  
Breast Cancer Patients ◽  
Relapse Free Survival ◽  
Free Survival ◽  
Favorable Prognosis ◽  
Cell Target

43 Background: Recognition of tumor cells by NK cells is mediated by the interaction of activating and inhibitory NK cell receptors with ligands expressed on the interacting cell. In addition to inhibitory and activating receptors, NK cells express adhesion molecules that allow conjugate formation between NK cells and their tumor targets. We have recently identified by transcriptional analysis of breast tumor specimens a signature of 5 genes, which included B cell response and interferon signaling, found to predict with > 85% accuracy relapse-free survival. In the current study we analyzed by gene expression profile, whether a differential expression of activatory and inhibitory receptors and gene involved in NK cell-target interactions could be identified in relapse and relapse free patients.Methods: RNA extraction and gene expression analysis was performed on tumor specimens with at least 10% of infiltrating cells deriving from 9 from breast cancer patients who had either 3-7 years relapse-free survival (n=9) or developed tumor relapse within 1-3 years after the initial treatment (n=8). Data were analyzed by BRB tools and Partek software.Results: Our results showed that patients with a favorable prognosis showed increased expression of genes involved in NK interaction with tumor cells and NK activating signaling. In particular an up-regulation of leukocyte function-associated antigen 1 (LFA-1) gene, typically involved in NK cells adhesion to target cells and DNAM 1, usually associated with activation of NK cells and considered one of the major protagonist of NK- Dendritic cells crosstalk, was observed to occur in relapse free patients. In addition, an up regulation of CD96 and CRTAM which, like DNAM 1, promote NK cell-target cell adhesion by interacting with the Necl2 and poliovirus receptor (PVR), was observed in relapse free patients. Conclusions: Our observation suggests that the NK signatures are associated with favorable outcome in breast cancer and allow us to generate new hypothesis on the role of innate immunity in this contest.

scholarly journals The tumor-infiltrating effector regulatory T cell:CD8+ lymphocyte ratio in invasive breast cancer

2019 ◽  
Author(s):  
Morihito Okada ◽  
Noriko Goda ◽  
Shinsuke Sasada ◽  
Hideo Shigematsu ◽  
Norio Masumoto ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Invasive Breast Cancer ◽  
Disease Free Survival ◽  
Tumor Infiltrating Lymphocytes ◽  
Breast Cancer Patients ◽  
Free Survival ◽  
Compete Response ◽  
Infiltrating Lymphocytes

Abstract Background Tumor-infiltrating lymphocytes (TILs) in breast cancer comprise immunostimulating and immunosuppressive components. Although FOXP3+ TILs are prototypical immunosuppressive TILs, only effector regulatory T cells (eTreg), a subset of immunosuppressive FOXP3+ TILs, are undetectable on immunohistochemical staining. This study aimed to evaluate the immunosuppressive potential of eTregs and the role of prototypical immunostimulatory CD8+ TILs in invasive breast cancer. Methods Fresh TILs extracted from 84 invasive breast cancer patients were analyzed via flow cytometry. We evaluated eTregs (CD4+FOXP3highCD45RA−), other FOXP3+ Treg subsets (naïve and non-Tregs), and total CD8+CD4- TILs. Clinicopathological factors, including histopathological characteristics, were also assessed. Results The median eTreg proportion of the total CD4+TILs was 18.7% (interquartile range [IQR], 16.4–25.5%); CD8+TILs, 124% (IQR, 87.5–140%). The proportion of eTregs to total FOXP3+ TILs varied (median, 65.6%; range, 10.1–93.2%). In an immunosuppression assay, only eTregs displayed potent immunosuppression; however, other Treg subsets did not. Among 39 patients who received neoadjuvant chemotherapy, eTreg subsets and pathological compete response (pCR) did not differ significantly, while pCR rates were significantly higher among individuals with a high than those with a low CD8+/eTreg ratio (90.2% vs 33.3%; P<0.05). Among all patients, a high CD8+/eTreg ratio tended to be associated with better disease-free survival rather than a low CD8+/eTreg ratio (P=0.09). Conclusions The CD8+/eTreg ratio is simple, optimal indicator of cancer immunity, and a high CD8+/eTreg ratio enhances the prognosis and treatment response in invasive breast cancer patients. However, further studies are required to validate the present findings.

scholarly journals The Role of Postoperative Radiotherapy After Primary Tumor Resection in Patients With De Novo Stage Iv Breast Cancer

2020 ◽  
Author(s):  
Yeon Joo Kim ◽  
Su Ssan Kim ◽  
Seung Do Ahn ◽  
Jinhong Jung ◽  
Sei-Hyun Ahn ◽  
...  
Keyword(s):  
Breast Cancer ◽  
De Novo ◽  
Postoperative Radiotherapy ◽  
Tumor Resection ◽  
Stage Iv ◽  
Breast Cancer Patients ◽  
Luminal A ◽  
Free Survival ◽  
Stage Iv Breast Cancer

Abstract Background: To investigate the role of postoperative radiotherapy (PORT) in stage IV breast cancer patients who underwent planned primary tumor resection (PTR).Methods: This study enrolled 112 patients diagnosed with de novo stage IV breast cancer who were treated with potentially curative PTR with or without PORT. The primary outcome was overall survival (OS), and the secondary outcomes were locoregional recurrence-free survival (LRRFS) and distant progression-free survival (DPFS).Results: At a median follow-up of 48.9 months (range, 3.5–183.4 months), the median OS was 54.9 months (range, 5.3–185.9 months) with a 5 year OS rate of 59.6%. Luminal A or B type tumors and PORT were significantly predictive of longer OS. The 5 year LRRFS and DMFS rates were 79.0% and 34.3%, respectively. PORT was the only significant predictor of LRRFS (hazard ratio [HR], 0.36; 95% confidence interval [CI], 0.15–0.86; p = 0.021). A comparison of patients who did and did not receive PORT showed that patients with disseminated metastasis more likely did not receive PORT and were excluded from the analysis. Multivariate analysis showed that PORT was significantly predictive of LRRFS (HR, 0.31; 95% CI, 0.11–0.91; p = 0.033) but not of OS. Conclusions: De novo stage IV breast cancer patients who received planned PTR showed favorable survival outcomes compared with historical cohorts. PTR may be predictive of a good prognosis, especially in patients with luminal A or B type tumors. PORT was significantly predictive of LRRFS, suggesting that patients may benefit from this treatment.Trial registration: The present study was not registered due to its retrospective nature.

scholarly journals Activation of PI3K/AKT/mTOR Pathway Causes Drug Resistance in Breast Cancer

2021 ◽  
Vol 12 ◽  
Author(s):  
Chao Dong ◽  
Jiao Wu ◽  
Yin Chen ◽  
Jianyun Nie ◽  
Ceshi Chen
Keyword(s):  
Breast Cancer ◽  
Drug Resistance ◽  
Cancer Progression ◽  
Critical Role ◽  
Acquired Resistance ◽  
Mtor Inhibitors ◽  
Disease Recurrence ◽  
Mtor Pathway ◽  
Breast Cancer Patients

Although chemotherapy, targeted therapy and endocrine therapy decrease rate of disease recurrence in most breast cancer patients, many patients exhibit acquired resistance. Hyperactivation of the PI3K/AKT/mTOR pathway is associated with drug resistance and cancer progression. Currently, a number of drugs targeting PI3K/AKT/mTOR are being investigated in clinical trials by combining them with standard therapies to overcome acquired resistance in breast cancer. In this review, we summarize the critical role of the PI3K/AKT/mTOR pathway in drug resistance, the development of PI3K/AKT/mTOR inhibitors, and strategies to overcome acquired resistance to standard therapies in breast cancer.

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