scholarly journals The Complex Interaction between the Tumor Micro-Environment and Immune Checkpoints in Breast Cancer

Cancers ◽  
2019 ◽  
Vol 11 (8) ◽  
pp. 1205 ◽  
Author(s):  
Vanessa Barriga ◽  
Nyanbol Kuol ◽  
Kulmira Nurgali ◽  
Vasso Apostolopoulos
Keyword(s):  
Breast Cancer ◽  
Tumor Microenvironment ◽  
Cancer Progression ◽  
Molecular Subtypes ◽  
Breast Cancer Subtype ◽  
Complex Interaction ◽  
Immune Checkpoints ◽  
Expression Studies ◽  
Cancer Subtype ◽  
Insight Into

The progression of breast cancer and its association with clinical outcome and treatment remain largely unexplored. Accumulating data has highlighted the interaction between cells of the immune system and the tumor microenvironment in cancer progression, and although studies have identified multiple facets of cancer progression within the development of the tumor microenvironment (TME) and its constituents, there is lack of research into the associations between breast cancer subtype and staging. Current literature has provided insight into the cells and pathways associated with breast cancer progression through expression analysis. However, there is lack of co-expression studies between immune pathways and cells of the TME that form pro-tumorigenic relationships contributing to immune-evasion. We focus on the immune checkpoint and TME elements that influence cancer progression, particularly studies in molecular subtypes of breast cancer.

scholarly journals Transposon mutagenesis identifies genes that cooperate with mutant Pten in breast cancer progression

2016 ◽  
Vol 113 (48) ◽  
pp. E7749-E7758 ◽  
Author(s):  
Roberto Rangel ◽  
Song-Choon Lee ◽  
Kenneth Hon-Kim Ban ◽  
Liliana Guzman-Rojas ◽  
Michael B. Mann ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Progression ◽  
Epithelial To Mesenchymal Transition ◽  
Breast Cancer Subtype ◽  
Clinical Importance ◽  
Transposon Mutagenesis ◽  
Phosphatase And Tensin Homolog ◽  
Mesenchymal Transition ◽  
Tensin Homolog ◽  
Cancer Subtype

Triple-negative breast cancer (TNBC) has the worst prognosis of any breast cancer subtype. To better understand the genetic forces driving TNBC, we performed a transposon mutagenesis screen in a phosphatase and tensin homolog (Pten) mutant mice and identified 12 candidate trunk drivers and a much larger number of progression genes. Validation studies identified eight TNBC tumor suppressor genes, including the GATA-like transcriptional repressorTRPS1. Down-regulation ofTRPS1in TNBC cells promoted epithelial-to-mesenchymal transition (EMT) by deregulating multiple EMT pathway genes, in addition to increasing the expression ofSERPINE1andSERPINB2and the subsequent migration, invasion, and metastasis of tumor cells. Transposon mutagenesis has thus provided a better understanding of the genetic forces driving TNBC and discovered genes with potential clinical importance in TNBC.

scholarly journals p63 at the Crossroads between Stemness and Metastasis in Breast Cancer

2019 ◽  
Vol 20 (11) ◽  
pp. 2683 ◽  
Author(s):  
Veronica Gatti ◽  
Lucilla Bongiorno-Borbone ◽  
Claudia Fierro ◽  
Margherita Annicchiarico-Petruzzelli ◽  
Gerry Melino ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Progression ◽  
Breast Cancer Subtype ◽  
Physiological Role ◽  
The Past ◽  
Cancer Breast ◽  
Incidence And Mortality ◽  
Cancer Subtype ◽  
Screening Approaches

After lung cancer, breast cancer (BC) is the most frequent cause of cancer death among women, worldwide. Although advances in screening approaches and targeted therapeutic agents have decreased BC incidence and mortality, over the past five years, triple-negative breast cancer (TNBC) remains the breast cancer subtype that displays the worst prognosis, mainly due to the lack of clinically actionable targets. Genetic and molecular profiling has unveiled the high intrinsic heterogeneity of TNBC, with the basal-like molecular subtypes representing the most diffuse TNBC subtypes, characterized by the expression of basal epithelial markers, such as the transcription factor p63. In this review, we will provide a broad picture on the physiological role of p63, in maintaining the basal epithelial identity, as well as its involvement in breast cancer progression, emphasizing its relevance in tumor cell invasion and stemness.

scholarly journals The relationship of tumor microenvironment and clinico-pathological parameters in different molecular subtypes of breast cancer

2021 ◽  
Author(s):  
Nina Čamdžić ◽  
Suada Kuskunović-Vlahovljak ◽  
Svjetlana Radović ◽  
Mirsad Dorić ◽  
Mirsad Babić ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Tumor Microenvironment ◽  
Cancer Progression ◽  
Molecular Subtypes ◽  
Molecular Subtype ◽  
Tumor Stroma ◽  
Histologic Grade ◽  
Clinicopathological Parameters ◽  
Immunohistochemical Expression ◽  
Ki 67

Introduction: Tumor microenvironment plays a significant role in tumor progression. Tumor stroma is one of the strongest modifiers of tumor cell response, cancer behavior, and cancer progression. This study aimed to investigate the correlation of matrix metalloproteinase-9 (MMP-9) expression and tumor-stroma ratio (TSR) with standard clinicopathological parameters in different molecular subtypes of breast cancer.Methods: Ninety biopsy samples of primary breast cancer diagnosed at the Department of Pathology, School of Medicine, Sarajevo, were selected for this study. The molecular subtype was determined based on the immunohistochemical expression of estrogen receptor, progesterone receptor, human epidermal growth factor receptor 2, and Ki-67. Stromal and tumoral MMP-9 immunohistochemical expression and the TSR were determined for each tumor.Results: Tumoral MMP-9 expression correlated positively with the presence of lymphovascular invasion (p= 0.016). TSR showed significant association and correlation with tumor grade (G) (p= 0.031; p= 0.049) and tumor size (pT) (p = 0.049;p= 0.021, respectively). Stromal MMP-9 expression correlated with histologic type, histologic grade of tumor, and lymphocytic inflammatory infiltrate (p= 0.021;p= 0.047, p= 0.038, respectively). A higher percentage of stromal MMP-9 expression correlated with the strongest lymphocytic response (p = 0.007). Significant correlation was observed between molecular subtypes and histologic grade of the tumor (p= 0.032).Conclusion: Our results, to some extent, confirm the significance of the tumor microenvironment in breast cancer, especially when it is about stromal MMP-9 expression. Although we observed significant association, without linear correlation, we found no significant correlation between molecular subtypes of breast cancer and MMP-9 expression.

scholarly journals Human Plasma Metabolomics for Biomarker Discovery: Targeting the Molecular Subtypes in Breast Cancer

Cancers ◽  
2021 ◽  
Vol 13 (1) ◽  
pp. 147
Author(s):  
Leticia Díaz-Beltrán ◽  
Carmen González-Olmedo ◽  
Natalia Luque-Caro ◽  
Caridad Díaz ◽  
Ariadna Martín-Blázquez ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Biomarker Discovery ◽  
Molecular Subtypes ◽  
Breast Cancer Subtype ◽  
P Value ◽  
Plasma Samples ◽  
Breast Cancer Patients ◽  
Clinical Value ◽  
Molecular Phenotypes

Purpose: The aim of this study is to identify differential metabolomic signatures in plasma samples of distinct subtypes of breast cancer patients that could be used in clinical practice as diagnostic biomarkers for these molecular phenotypes and to provide a more individualized and accurate therapeutic procedure. Methods: Untargeted LC-HRMS metabolomics approach in positive and negative electrospray ionization mode was used to analyze plasma samples from LA, LB, HER2+ and TN breast cancer patients and healthy controls in order to determine specific metabolomic profiles through univariate and multivariate statistical data analysis. Results: We tentatively identified altered metabolites displaying concentration variations among the four breast cancer molecular subtypes. We found a biomarker panel of 5 candidates in LA, 7 in LB, 5 in HER2 and 3 in TN that were able to discriminate each breast cancer subtype with a false discovery range corrected p-value < 0.05 and a fold-change cutoff value > 1.3. The model clinical value was evaluated with the AUROC, providing diagnostic capacities above 0.85. Conclusion: Our study identifies metabolic profiling differences in molecular phenotypes of breast cancer. This may represent a key step towards therapy improvement in personalized medicine and prioritization of tailored therapeutic intervention strategies.

scholarly journals Erratum to: Contribution of clinical and socioeconomic factors to differences in breast cancer subtype and mortality between Hispanic and non-Hispanic white women

2017 ◽  
Vol 166 (1) ◽  
pp. 195-195 ◽  
Author(s):  
María Elena Martínez ◽  
Scarlett L. Gomez ◽  
Li Tao ◽  
Rosemary Cress ◽  
Danielle Rodriguez ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Socioeconomic Factors ◽  
White Women ◽  
Breast Cancer Subtype ◽  
Cancer Subtype ◽  
Hispanic White

scholarly journals Integrative analysis of mRNA and miRNA profiles identifies miR-193 and miR-210 as potential regulatory biomarkers in different molecular subtypes of breast cancer

2020 ◽  
Author(s):  
Adriane Feijo Evangelista ◽  
Renato J Oliveira ◽  
Viviane A O Silva ◽  
Rene A D C Vieira ◽  
Rui M Reis ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Proliferation ◽  
Cell Line ◽  
Cell Lines ◽  
Breast Cancer Cell ◽  
Cancer Progression ◽  
Triple Negative ◽  
Molecular Subtypes ◽  
Breast Cancer Cell Lines ◽  
Mcf 7

Abstract Introduction: Breast cancer is the most frequently diagnosed malignancy among women. However, the role of microRNA expression in breast cancer progression is not fully understood. In this study we examined predictive interactions between differentially expressed miRNAs and mRNAs in breast cancer cell lines representative of the common molecular subtypes. Integrative bioinformatics analysis identified miR-193 and miR-210 as potential regulatory biomarkers of mRNA in breast cancer. Several recent studies have investigated these miRNAs in a broad range of tumors, but the mechanism of their involvement in cancer progression has not previously been investigated. Methods: The miRNA-mRNA interactions in breast cancer cell lines were identified by parallel expression analysis and miRNA target prediction programs. The expression profiles of mRNA and miRNAs from luminal (MCF-7, MCF-7/AZ and T47D), HER2 (BT20 and SK-BR3) and triple negative subtypes (Hs578T e MDA-MB-231) could be clearly separated by unsupervised analysis using HB4A cell line as a control. Breast cancer miRNA data from TCGA patients were grouped according to molecular subtypes and then used to validate these findings. Expression of miR-193 and miR-210 was investigated by miRNA transient silencing assays using the MCF7, BT20 and MDA-MB-231 cell lines. Functional studies included, xCELLigence system, ApoTox-Glo triplex, flow cytometry and transwell assays were performed to determine cell proliferation, cytotoxicity, apoptosis, migration and invasion, respectively. Results: The most evident effects were associated with cell proliferation after miR-210 silencing in triple negative subtype cell line MDA-MB-231. Using in silico prediction algorithms, TNFRSF10 was identified as one of the potential downstream targets for both miRNAs. The TNFRSF10C and TNFRSF10D mRNA expression inversely correlated with the expression levels of miR-193 and miR210 in breast cell lines and breast cancer patients, respectively. Other potential regulated genes whose expression also inversely correlated with both miRNAs were CCND1, a mediator on invasion and metastasis, and the tumor suppressor gene RUNX3. Conclusion: In summary, our findings identify miR-193 and miR-210 as potential regulatory miRNA in different molecular subtypes of breast cancer and suggest that miR-210 may have specific role in MDA-MB-231 proliferation. Our results highlight important new downstream regulated targets that may serve as promising therapeutic pathways for aggressive breast cancers.

scholarly journals Ki-67 as a prognostic marker according to breast cancer subtype and a predictor of recurrence time in primary breast cancer

2010 ◽  
Vol 1 (5) ◽  
pp. 747-754 ◽  
Author(s):  
REIKI NISHIMURA ◽  
TOMOFUMI OSAKO ◽  
YASUHIRO OKUMURA ◽  
MITSUHIRO HAYASHI ◽  
YASUO TOYOZUMI ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Prognostic Marker ◽  
Primary Breast Cancer ◽  
Breast Cancer Subtype ◽  
Recurrence Time ◽  
Ki 67 ◽  
Cancer Subtype

Immunohistochemical Profiles of Breast Cancer Patients at MRCCC Siloam Semanggi Hospital in 2018

2021 ◽  
Vol 11 (5) ◽  
pp. 392-400
Author(s):  
Fajar Lamhot Gultom ◽  
Marliana Nurprilinda ◽  
Ryani Nur Cahyaning Hutami
Keyword(s):  
Breast Cancer ◽  
Breast Cancer Subtype ◽  
Breast Cancer Patients ◽  
Ki 67 ◽  
Proliferation Markers ◽  
Luminal B ◽  
Cancer Subtype ◽  
Anatomy Laboratory ◽  
Grade Ii ◽  
Her 2

Immunohistochemistry examination (IHC) is one of the additional tests to diagnose and determine breast cancer subtype. IHC examination is a method to check intracellular protein using a monoclonal and polyclonal antibody to detect the antigen in tissue. IHC examination determined by hormone receptor markers (ER and PR), HER-2/Neu expression, and apoptotic and proliferation markers (Ki-67 and p53) can be used to determine therapy and prognosis. This study aims to determine the hormonal status of breast cancer patient at Siloam Semanggi Hospital in 2018, in the form of age, gender, pathology diagnose, and the result of IHC (ER, PR, HER2, and Ki-67). This study is a retrospective descriptive study using pathological anatomy laboratory results of breast cancer in MRCCC Siloam Semanggi Hospital and 208 patients following inclusion and exclusion criteria. The result obtained is that the age group with the highest frequency is 50-59 years, with 34.1%. The highest frequency by gender is a woman with 99.5%. Carcinoma mammae NST with grade II and III was found in 38.0% of patients. The hormonal receptor with ER and PR positive was found in 51.0% of patients. HER2 expression negative was found in 56.7% of patients. High proliferation Ki-67 was found in 82.7% of patients. Luminal B with HER2 negative subtype was found in 32.2% of patients. Patients in 50-59 years with Luminal B with HER2 negative subtype was found in 26 patients. Patients in carcinoma mammae NST with grade II with Luminal B with HER2 negative subtype was found in 27 patients. Keywords: Breast cancer, pathologic anatomy, immunohistochemistry, breast cancer subtype

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