scholarly journals Prognostic value of CD8 + PD-1+ immune infiltrates and PDCD1 gene expression in triple negative breast cancer

2019 ◽  
Vol 7 (1) ◽  
Author(s):  
Joe Yeong ◽  
Jeffrey Chun Tatt Lim ◽  
Bernett Lee ◽  
Huihua Li ◽  
Clara Chong Hui Ong ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Triple Negative Breast Cancer ◽  
Prognostic Value ◽  
Triple Negative

scholarly journals Prognostic Significance and Tumor Immune Microenvironment Heterogenicity of m5C RNA Methylation Regulators in Triple-Negative Breast Cancer

2021 ◽  
Vol 9 ◽  
Author(s):  
Zhidong Huang ◽  
Junfan Pan ◽  
Helin Wang ◽  
Xianqiang Du ◽  
Yusheng Xu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Triple Negative Breast Cancer ◽  
Prognostic Value ◽  
Triple Negative ◽  
Gene Set Enrichment Analysis ◽  
Immune Microenvironment ◽  
Data Set ◽  
Rna Methylation ◽  
Tumor Immune Microenvironment

PurposeThe m5C RNA methylation regulators are closely related to tumor proliferation, occurrence, and metastasis. This study aimed to investigate the gene expression, clinicopathological characteristics, and prognostic value of m5C regulators in triple-negative breast cancer (TNBC) and their correlation with the tumor immune microenvironment (TIM).MethodsThe TNBC data, Luminal BC data and HER2 positive BC data set were obtained from The Cancer Genome Atlas and Gene Expression Omnibus, and 11 m5C RNA methylation regulators were analyzed. Univariate Cox regression and the least absolute shrinkage and selection operator regression models were used to develop a prognostic risk signature. The UALCAN and cBioportal databases were used to analyze the gene characteristics and gene alteration frequency of prognosis-related m5C RNA methylation regulators. Gene set enrichment analysis was used to analyze cellular pathways enriched by prognostic factors. The Tumor Immune Single Cell Hub (TISCH) and Timer online databases were used to explore the relationship between prognosis-related genes and the TIM.ResultsMost of the 11 m5C RNA methylation regulators were differentially expressed in TNBC and normal samples. The prognostic risk signature showed good reliability and an independent prognostic value. Prognosis-related gene mutations were mainly amplified. Concurrently, the NOP2/Sun domain family member 2 (NSUN2) upregulation was closely related to spliceosome, RNA degradation, cell cycle signaling pathways, and RNA polymerase. Meanwhile, NSUN6 downregulation was related to extracellular matrix receptor interaction, metabolism, and cell adhesion. Analysis of the TISCH and Timer databases showed that prognosis-related genes affected the TIM, and the subtypes of immune-infiltrating cells differed between NSUN2 and NSUN6.ConclusionRegulatory factors of m5C RNA methylation can predict the clinical prognostic risk of TNBC patients and affect tumor development and the TIM. Thus, they have the potential to be a novel prognostic marker of TNBC, providing clues for understanding the RNA epigenetic modification of TNBC.

scholarly journals An open-label, pilot study of veliparib and lapatinib in patients with metastatic, triple-negative breast cancer

2021 ◽  
Vol 23 (1) ◽  
Author(s):  
Erica M. Stringer-Reasor ◽  
Jori E. May ◽  
Eva Olariu ◽  
Valerie Caterinicchia ◽  
Yufeng Li ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Dna Repair ◽  
Pilot Study ◽  
Expression Analysis ◽  
Triple Negative Breast Cancer ◽  
Gene Expression Analysis ◽  
Triple Negative ◽  
Egfr Inhibition ◽  
Link Type

Abstract Background Poly (ADP-ribose)-polymerase inhibitors (PARPi) have been approved for cancer patients with germline BRCA1/2 (gBRCA1/2) mutations, and efforts to expand the utility of PARPi beyond BRCA1/2 are ongoing. In preclinical models of triple-negative breast cancer (TNBC) with intact DNA repair, we have previously shown an induced synthetic lethality with combined EGFR inhibition and PARPi. Here, we report the safety and clinical activity of lapatinib and veliparib in patients with metastatic TNBC. Methods A first-in-human, pilot study of lapatinib and veliparib was conducted in metastatic TNBC (NCT02158507). The primary endpoint was safety and tolerability. Secondary endpoints were objective response rates and pharmacokinetic evaluation. Gene expression analysis of pre-treatment tumor biopsies was performed. Key eligibility included TNBC patients with measurable disease and prior anthracycline-based and taxane chemotherapy. Patients with gBRCA1/2 mutations were excluded. Results Twenty patients were enrolled, of which 17 were evaluable for response. The median number of prior therapies in the metastatic setting was 1 (range 0–2). Fifty percent of patients were Caucasian, 45% African–American, and 5% Hispanic. Of evaluable patients, 4 demonstrated a partial response and 2 had stable disease. There were no dose-limiting toxicities. Most AEs were limited to grade 1 or 2 and no drug–drug interactions noted. Exploratory gene expression analysis suggested baseline DNA repair pathway score was lower and baseline immunogenicity was higher in the responders compared to non-responders. Conclusions Lapatinib plus veliparib therapy has a manageable safety profile and promising antitumor activity in advanced TNBC. Further investigation of dual therapy with EGFR inhibition and PARP inhibition is needed. Trial registration ClinicalTrials.gov, NCT02158507. Registered on 12 September 2014

scholarly journals WEE1 Dependency and Pejorative Prognostic Value in Triple‐Negative Breast Cancer

2021 ◽  
pp. 2101030
Author(s):  
Alexandre Nonneville ◽  
Pascal Finetti ◽  
Daniel Birnbaum ◽  
Emilie Mamessier ◽  
François Bertucci
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Prognostic Value ◽  
Triple Negative

scholarly journals The BIRC Family Genes Expression in Patients with Triple Negative Breast Cancer

2021 ◽  
Vol 22 (4) ◽  
pp. 1820
Author(s):  
Anna Makuch-Kocka ◽  
Janusz Kocki ◽  
Anna Brzozowska ◽  
Jacek Bogucki ◽  
Przemysław Kołodziej ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Clinical Data ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Lymphatic Vessels ◽  
The Cancer Genome Atlas ◽  
Expression Level ◽  
Cancer Tissue ◽  
Expression Levels

The BIRC (baculoviral IAP repeat-containing; BIRC) family genes encode for Inhibitor of Apoptosis (IAP) proteins. The dysregulation of the expression levels of the genes in question in cancer tissue as compared to normal tissue suggests that the apoptosis process in cancer cells was disturbed, which may be associated with the development and chemoresistance of triple negative breast cancer (TNBC). In our study, we determined the expression level of eight genes from the BIRC family using the Real-Time PCR method in patients with TNBC and compared the obtained results with clinical data. Additionally, using bioinformatics tools (Ualcan and The Breast Cancer Gene-Expression Miner v4.5 (bc-GenExMiner v4.5)), we compared our data with the data in the Cancer Genome Atlas (TCGA) database. We observed diverse expression pattern among the studied genes in breast cancer tissue. Comparing the expression level of the studied genes with the clinical data, we found that in patients diagnosed with breast cancer under the age of 50, the expression levels of all studied genes were higher compared to patients diagnosed after the age of 50. We observed that in patients with invasion of neoplastic cells into lymphatic vessels and fat tissue, the expression levels of BIRC family genes were lower compared to patients in whom these features were not noted. Statistically significant differences in gene expression were also noted in patients classified into three groups depending on the basis of the Scarff-Bloom and Richardson (SBR) Grading System.

Prognostic value of IMP3 expression as a determinant of chemosensitivity in triple-negative breast cancer

2017 ◽  
Vol 213 (9) ◽  
pp. 1160-1165 ◽  
Author(s):  
Ryuji Ohashi ◽  
Maoka Sangen ◽  
Shigeki Namimatsu ◽  
Keiko Yanagihara ◽  
Koji Yamashita ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Prognostic Value ◽  
Triple Negative

Prognostic Value of Tumor-Infiltrating Lymphocytes in Triple-Negative Breast Cancer

2015 ◽  
Vol 7 (4) ◽  
pp. 232-241
Author(s):  
Koo Si-Lin ◽  
Loh Kiley ◽  
Sulastri Kamis ◽  
Jabed Iqbal ◽  
Rebecca Dent ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Prognostic Value ◽  
Triple Negative ◽  
Tumor Infiltrating Lymphocytes ◽  
Infiltrating Lymphocytes

scholarly journals Breast Cancer Type Classification Using Machine Learning

2021 ◽  
Vol 11 (2) ◽  
pp. 61
Author(s):  
Jiande Wu ◽  
Chindo Hicks
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Machine Learning ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Genomic Research ◽  
Support Vector ◽  
Cancer Type ◽  
Classification Models

Background: Breast cancer is a heterogeneous disease defined by molecular types and subtypes. Advances in genomic research have enabled use of precision medicine in clinical management of breast cancer. A critical unmet medical need is distinguishing triple negative breast cancer, the most aggressive and lethal form of breast cancer, from non-triple negative breast cancer. Here we propose use of a machine learning (ML) approach for classification of triple negative breast cancer and non-triple negative breast cancer patients using gene expression data. Methods: We performed analysis of RNA-Sequence data from 110 triple negative and 992 non-triple negative breast cancer tumor samples from The Cancer Genome Atlas to select the features (genes) used in the development and validation of the classification models. We evaluated four different classification models including Support Vector Machines, K-nearest neighbor, Naïve Bayes and Decision tree using features selected at different threshold levels to train the models for classifying the two types of breast cancer. For performance evaluation and validation, the proposed methods were applied to independent gene expression datasets. Results: Among the four ML algorithms evaluated, the Support Vector Machine algorithm was able to classify breast cancer more accurately into triple negative and non-triple negative breast cancer and had less misclassification errors than the other three algorithms evaluated. Conclusions: The prediction results show that ML algorithms are efficient and can be used for classification of breast cancer into triple negative and non-triple negative breast cancer types.

Retrospective Study about the Prevalence of (TILs) Tumor Infiltrating Lymphocytes in Non-Metastatic Triple Negative Breast Cancer Patients and its Prognostic Value

QJM ◽  
2021 ◽  
Vol 114 (Supplement_1) ◽  
Author(s):  
Hesham Ahmed ElGhazaly ◽  
Manal Mohamed El-Mahdy ◽  
Azza Mohamed Adel ◽  
Nermeen Mostafa ◽  
Aya Magdy Kamal Ali
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Retrospective Study ◽  
Triple Negative Breast Cancer ◽  
Prognostic Value ◽  
Triple Negative ◽  
Free Survival ◽  
Female Patients ◽  
Risk Of Death ◽  
Reduced Risk

Abstract Background TNBC comprises a distinct disease entity with a unique microenvironment of TILs, the immunogenic potential of TNBC is derived from its genetic instability and high mutation rate. Tumors from patients with TNBC are more likely than tumors from patients with other subtypes to exhibit chromosomal instability and potential mutations. Objectives The study aims to evaluate the prevalence of CD8+ TILs biomarker by IHC in triple negative breast cancer and its prognostic value. TILs are an important prognostic value for the response of patient to chemotherapy the greater number of TILS is associated with higher probability of response to chemotherapy also decrease recurrence. TILS in triple negative breast cancer suggest a likely option for immunotherapy in this disease. Patients and Methods This is a retrospective study, which was carried on 30 female patients, Clinical data and paraffin wax block of female patients with triple negative breast cancer are to be collected from the breast cancer unit, department of clinical Oncology and Nuclear medicine Ain Shams university and Matarya teaching hospital. Results Several large systematic reviews and meta-analyses have confirmed that high levels of TILs are associated with better disease free survival and overall survival only in triple negative and HER2 positive subtypes, with no significant benefit seen in estrogen receptor positive breast carcinoma. In the Breast International Group (BIG) 02-98 trial shows that for every 10% increase in the intertumoral TILs there was a 17% reduced risk of relapse, and 27% reduced risk of death regardless of chemotherapy type. Also in eastern cooperative oncology group trial (ECOG) 2197, and 1199 showed that for every 10% increase in TILs, a 14% reduction of risk of recurrence, and 19% reduction in risk of death were observed. Conclusion Our study showed that All our patients (100%) were positive for CD8+, with a minimum range of 1% and a maximum range of 60%, most of the patients (20 patients) had CD8% between (10% to 20%). High levels of CD8 + TILs are good prognostic indicators in TNBC. our study showed that there were associations of CD8+ TILs infiltrate status with longer progression free survival and better overall survival in triple-negative breast cancer, but were not statistically significant probably due to our small sample size.

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