scholarly journals Immune Milieu and Genomic Alterations Set the Triple-Negative Breast Cancer Immunomodulatory Subtype Tumor Behavior

Cancers ◽  
2021 ◽  
Vol 13 (24) ◽  
pp. 6256
Author(s):  
Rubén Rodríguez-Bautista ◽  
Claudia H. Caro-Sánchez ◽  
Paula Cabrera-Galeana ◽  
Gerardo J. Alanis-Funes ◽  
Everardo Gutierrez-Millán ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Immune System ◽  
Dna Sequencing ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Expression Patterns ◽  
Tumor Biology ◽  
Enrichment Analysis ◽  
Gene Set Enrichment Analysis ◽  
Genomic Alterations

Triple-negative breast cancer (TNBC) is an aggressive and heterogeneous disease. Seven subtypes have been described based on gene expression patterns. Herein, we characterized the tumor biology and clinical behavior of the immunomodulatory (IM) subtype. Methods: Formalin-fixed paraffin-embedded tumor samples from 68 high-risk (stage III-IV) TNBC patients were analyzed through microarrays, immunohistochemistry, and DNA sequencing. Results: The IM subtype was identified in 24% of TNBC tumor samples and characterized by a higher intratumoral (intT) and stromal (strml) infiltration of FOXP3+ TILs (Treg) compared with non-IM subtypes. Further, PD-L1+ (>1%) expression was significantly higher, as well as CTLA-4+ intT and strml expression in the IM subtype. Differential expression and gene set enrichment analysis identified biological processes associated with the immune system. Pathway analysis revealed enrichment of the β-catenin signaling pathway. The non-coding analysis led to seven Long Intergenic Non-Protein Coding RNAs (lincRNAs) (6 up-regulated and 1 down-regulated) that were associated with a favorable prognosis in the TNBC-IM subtype. The DNA sequencing highlighted two genes relevant to immune system responses: CTNNB1 (Catenin β-1) and IDH1. Conclusion: the IM subtype showed a distinct immune microenvironment, as well as subtype-specific genomic alterations. Characterizing TNBC at a molecular and transcriptomic level might guide immune-based therapy in this subgroup of patients.

scholarly journals Panoptic Overview of Triple-Negative Breast Cancer in Nigeria: Current Challenges and Promising Global Initiatives

2018 ◽  
pp. 1-20
Author(s):  
Nikita Wright ◽  
Padmashree Rida ◽  
Emad Rakha ◽  
Ayodeji Agboola ◽  
Ritu Aneja
Keyword(s):  
Breast Cancer ◽  
United States ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Resource Constraints ◽  
African Ancestry ◽  
Expression Patterns ◽  
Tumor Biology ◽  
The United States ◽  
Nigerian Women

PurposeTriple-negative breast cancer (TNBC) is the most deadly form of breast cancer (BC) today. TNBC treatment is fraught with challenges because of the extensive interpatient heterogeneity in clinical behavior and scarcity of stratifying biomarkers and actionable targets. Women of African ancestry face a disproportionate burden resulting from this disease, which affects them earlier and more aggressively and has a higher propensity to spread and resist conventional treatments. A much higher proportion of Nigerian patients with BC have TNBC compared with patients with BC in the United States and Europe.MethodsThis article spotlights Nigeria as an example of a nation wherein genetic and nongenetic spheres of influence intersect to affect the prevalence of this disease, the scale of its challenge, and its toll.ResultsStudies have illuminated the inherently different tumor biology of Nigerian TNBCs, which show distinct genetic variants and gene expression patterns compared with European or European-American TNBCs. Parallels are apparent between TNBC phenotypes among African Americans and Nigerians, implicating the common thread of shared genetic ancestry between these populations. Reproductive, lifestyle, socioeconomic, and cultural factors also shape TNBC outcomes in Nigeria, as do resource constraints in Nigerian health care and research sectors.ConclusionIncreasing our understanding of how these factors contribute to poorer outcomes among Nigerian women may uncover valuable insights and strategies in alleviating the TNBC burden in many countries of the world and help reduce the racial disparity in BC-related outcomes here in the United States. Importantly, this review also highlights collaborative global and local initiatives that converge expertise and resources to advance research on effective management of TNBC in diverse populations.

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.

scholarly journals GBP5 Serves as a Potential Marker to Predict a Favorable Response in Triple-Negative Breast Cancer Patients Receiving a Taxane-Based Chemotherapy

2021 ◽  
Vol 11 (3) ◽  
pp. 197
Author(s):  
Shun-Wen Cheng ◽  
Po-Chih Chen ◽  
Tzong-Rong Ger ◽  
Hui-Wen Chiu ◽  
Yuan-Feng Lin
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Computational Simulation ◽  
Prognostic Significance ◽  
Enrichment Analysis ◽  
Gene Set Enrichment Analysis ◽  
Breast Cancer Patients ◽  
Potential Marker ◽  
Signaling Axis

Pre-operative (neoadjuvant) or post-operative (adjuvant) taxane-based chemotherapy is still commonly used to treat patients with triple-negative breast cancer (TNBC). However, there are still no effective biomarkers used to predict the responsiveness and efficacy of taxane-based chemotherapy in TNBC patients. Here we find that guanylate-binding protein 5 (GBP5), compared to other GBPs, exhibits the strongest prognostic significance in predicting TNBC recurrence and progression. Whereas GBP5 upregulation showed no prognostic significance in non-TNBC patients, a higher GBP5 level predicted a favorable recurrence and progression-free condition in the TNBC cohort. Moreover, we found that GBP5 expression negatively correlated with the 50% inhibitory concentration (IC50) of paclitaxel in a panel of TNBC cell lines. The gene knockdown of GBP5 increased the IC50 of paclitaxel in the tested TNBC cells. In TNBC patients receiving neoadjuvant or adjuvant chemotherapy, a higher GBP5 level strongly predicted a good responsiveness. Computational simulation by the Gene Set Enrichment Analysis program and cell-based assays demonstrated that GBP5 probably enhances the cytotoxic effectiveness of paclitaxel via activating the Akt/mTOR signaling axis and suppressing autophagy formation in TNBC cells. These findings suggest that GBP5 could be a good biomarker to predict a favorable outcome in TNBC patients who decide to receive a taxane-based neoadjuvant or adjuvant therapy.

Essential amino acid metabolism-related molecular classification in triple-negative breast cancer

Epigenomics ◽  
2021 ◽  
Vol 13 (16) ◽  
pp. 1247-1268
Author(s):  
Yajie Zhao ◽  
Chunrui Pu ◽  
Dechuang Jiao ◽  
Jiujun Zhu ◽  
Xuhui Guo ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Amino Acid ◽  
Triple Negative Breast Cancer ◽  
Immune Checkpoint ◽  
Essential Amino Acid ◽  
Triple Negative ◽  
Expression Patterns ◽  
Molecular Classification ◽  
Biological Insight ◽  
Metabolic Heterogeneity

Aim: To develop an approach to characterize and classify triple-negative breast cancer (TNBC) tumors based upon their essential amino acid (EAA) metabolic activity. Methods: We performed bioinformatic analyses of genomic, transcriptomic and clinical data in an integrated cohort of 740 TNBC patients from public databases. Results: Based on EAA metabolism-related gene expression patterns, two TNBC subtypes were identified with distinct prognoses and genomic alterations. Patients exhibiting an upregulated EAA metabolism phenotype were more prone to chemoresistance but also expressed higher levels of immune checkpoint genes and may be better candidates for immune checkpoint inhibitor therapy. Conclusion: Metabolic classification based upon EAA profiles offers a novel biological insight into previously established TNBC subtypes and advances current understanding of TNBC’s metabolic heterogeneity.

Expression patterns of claudins in patients with triple-negative breast cancer are associated with nodal metastasis and worse outcome

2017 ◽  
Vol 67 (8) ◽  
pp. 404-413 ◽  
Author(s):  
Ayaka Katayama ◽  
Tadashi Handa ◽  
Kei Komatsu ◽  
Maria Togo ◽  
Jun Horiguchi ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Expression Patterns ◽  
Nodal Metastasis

Expression patterns of GATA3 and the androgen receptor are strongly correlated in patients with triple-negative breast cancer

2016 ◽  
Vol 55 ◽  
pp. 190-195 ◽  
Author(s):  
Sewha Kim ◽  
Byung-In Moon ◽  
Woosung Lim ◽  
Sanghui Park ◽  
Min Sun Cho ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Androgen Receptor ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Expression Patterns ◽  
Strongly Correlated

scholarly journals Profile and Outcome of Triple Negative Breast Cancer at a Tertiary Care University Hospital in Nepal

2020 ◽  
Vol 5 (2) ◽  
pp. 101-105
Author(s):  
Suman Khanal ◽  
Yogendra P. Singh ◽  
Gita Sayami ◽  
Akihiko Ozaki
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Ductal Carcinoma ◽  
Tertiary Care ◽  
Tumor Biology ◽  
Clinical Profile ◽  
University Teaching ◽  
University Hospital ◽  
P Value

Background: TNBC (Triple negative breast cancer) subtype (ER-/PR-/HER2-) of breast cancers are known for aggressive tumor biology and poor survival prospects, with high early relapse rate. However, little is known about the prevalence and characteristics of TNBC breast cancer in Nepal. Objectives: To clarify the geographical distribution, clinical profile and outcome of TNBC patients when compared with non-TNBC patients managed in tertiary care university hospital in Nepal. Materials and Methods: This is a study on prospective observational analyses of TNBC and non-TNBC patients managed at Tribhuvan University Teaching Hospital, Kathmandu from October 2015-March 2018. We collected and analyzed data on clinical profile, pathological tumor features and outcome of the two patient groups. Results: A total of 108 breast cancer patients were included in our study, 38 (35.2%) of which were TNBCs. Mean age at diagnosis was 49±12 years. Majority of TNBCs (29%) were concentrated in Terai districts compared to non-TNBCs (18.6%). Among TNBCs, 15.2% had tumor size 5 cm or more while only 11.9% had such finding in non-TNBCs. Majority of TNBCs and non-TNBCs were of invasive ductal carcinoma of NST histology (76.3 vs 90%). TNBC tumors were significantly of grade 3 (P value=0.003). Perineural invasion was seen more (15.8%) in TNBCs compared to 8.96% in non-TNBCs. On average, 23.6% of total nodes retrieved from axilla were positive for tumor in TNBCs compared to 21% in non-TNBCs. Three patients developed metastases in TNBCs of which two were to brain while 5 had metastases in non-TNBC with none to brain. Higher percentage of patients died in TNBC group (13.2 vs 7.1%). Conclusions: TNBCs are quite common, higher grade tumors with brain metastasis without particular geographic distribution.

scholarly journals GLUT1 inhibition blocks growth of RB1-positive Triple Negative Breast Cancer

2019 ◽  
Author(s):  
Qin Wu ◽  
Wail ba-alawi ◽  
Genevieve Deblois ◽  
Jennifer Cruickshank ◽  
Shili Duan ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Glucose Transporter ◽  
Triple Negative ◽  
Enrichment Analysis ◽  
Pathway Enrichment Analysis ◽  
Glucose Transporter 1 ◽  
Protein Levels ◽  
Development Of Resistance ◽  
Retinoblastoma Tumor

AbstractTriple negative breast cancer (TNBC) is a deadly form of breast cancer due to the development of resistance to chemotherapy affecting over 30% of patients. New therapeutics and companion biomarkers are urgently needed. Recognizing the elevated expression of glucose transporter 1 (GLUT1, encoded by SLC2A1) and associated metabolic dependencies in TNBC, we investigated the vulnerability of TNBC cell lines and patient-derived samples to GLUT1 inhibition. We report that genetic or pharmacological inhibition of GLUT1 with BAY-876 impairs the growth of a subset of TNBC cells displaying high glycolytic and lower oxidative phosphorylation (OXPHOS) rates. Pathway enrichment analysis of gene expression data implicates E2F Targets pathway activity as a surrogate of OXPHOS activity. Furthermore, the protein levels of retinoblastoma tumor suppressor (RB1) are strongly correlated with the degree of sensitivity to GLUT1 inhibition in TNBC, where RB1-negative cells are insensitive to GLUT1 inhibition. Collectively, our results highlight a strong and targetable RB1-GLUT1 metabolic axis in TNBC and warrant clinical evaluation of GLUT1 inhibition in TNBC patients stratified according to RB1 protein expression levels.

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