The latest progress in research on triple negative breast cancer (TNBC): risk factors, possible therapeutic targets and prognostic markers.
Ontology highlight
ABSTRACT:
SUBMITTER: Jiao Q
PROVIDER: S-EPMC4178098 | biostudies-literature | 2014 Sep
REPOSITORIES: biostudies-literature
Publications
The latest progress in research on triple negative breast cancer (TNBC): risk factors, possible therapeutic targets and prognostic markers.
Jiao Qingli Q Wu Aiguo A Shao Guoli G Peng Haoyu H Wang Mengchuan M Ji Shufeng S Liu Peng P Zhang Jian J
Journal of thoracic disease 20140901 9
Triple negative breast cancer (TNBC) is one type of breast cancer (BC), which is defined as negative for estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor-2 (Her2). Its origins and development seem to be elusive. And for now, drugs like tamoxifen or trastuzumab which specifically apply to ER, PR or Her2 positive BC seem unforeseeable in TNBC clinical treatment. Due to its extreme malignancy, high recurrence rate and poor prognosis, a lot of work on the ...[more]
Similar Datasets
Project description:There are no widely-accepted prognostic markers currently available to predict outcomes in patients with triple-negative breast cancer (TNBC), and no targeted therapies with confirmed benefit. We have used MALDI mass spectrometry imaging (MSI) of tryptic peptides to compare regions of cancer and benign tissue in 10 formalin-fixed, paraffin-embedded sections of TNBC tumors. Proteins were identified by reference to a peptide library constructed by LC-MALDI-MS/MS analyses of the same tissues. The prognostic significance of proteins that distinguished between cancer and benign regions was estimated by Kaplan-Meier analysis of their gene expression from public databases. Among peptides that distinguished between cancer and benign tissue in at least 3 tissues with a ROC area under the curve >0.7, 14 represented proteins identified from the reference library, including proteins not previously associated with breast cancer. Initial network analysis using the STRING database showed no obvious functional relationships except among collagen subunits COL1A1, COL1A2, and COL63A, but manual curation, including the addition of EGFR to the analysis, revealed a unique network connecting 10 of the 14 proteins. Kaplan-Meier survival analysis to examine the relationship between tumor expression of genes encoding the 14 proteins, and recurrence-free survival (RFS) in patients with basal-like TNBC showed that, compared to low expression, high expression of nine of the genes was associated with significantly worse RFS, most with hazard ratios >2. In contrast, in estrogen receptor-positive tumors, high expression of these genes showed only low, or no, association with worse RFS. These proteins are proposed as putative markers of RFS in TNBC, and some may also be considered as possible targets for future therapies.
2019-05-06 | PXD013397 | Pride
Project description:Background: Triple-negative breast cancer (TNBC) is a complex and molecularly heterogeneous entity, with the poorest outcome compared with other breast cancer subtypes. Previously, we developed a TNBC 3-gene score with a significant prognostic capability. This study aims to test the 3-gene score in the different TNBC subtypes. Methods: Data from 204 TNBC patients treated with neoadjuvant chemotherapy were retrieved from public datasets and pooled (GSE25066, GSE58812, and GSE16446). After removing batch effects, cases were classified into Lehman’s TNBC subtypes and then the TNBC 3-gene score was used to evaluate the risk of distant recurrence in each subgroup. In addition, the association with tumor-infiltrating lymphocyte (TILs) levels was evaluated in a retrospective group of 72 TNBC cases. Results: The TNBC 3-gene score was able to discriminate patients with different risks within the pooled cohort (HR = 2.41 for high vs. low risk; 95%CI: 1.50−3.86). The score showed predictive capability in the immunomodulatory subtype (HR = 4.16; 95%CI: 1.63−10.60) and in the mesenchymal stem-like subtype (HR = 18.76; 95%CI: 1.68−208.97). In the basal-like 1, basal-like-2, and mesenchymal subtypes, the observed differential risk patterns showed no statistical significance. The score had poor predictive capability in the luminal androgen receptor subtype (p = 0.765). In addition, a low TNBC 3-gene score was related to a high level of TIL infiltration (p < 0.001). Conclusions: The TNBC 3-gene score is able to predict the risk of distant recurrence in TNBC patients, specifically in the immunomodulatory and mesenchymal stem-like subtype. Despite a small sample size in each subgroup, an improved prognostic capability was seen in TNBC subtypes with tumor-infiltrating components.
| S-EPMC9454544 | biostudies-literature
Project description:Triple‑negative breast cancer (TNBC) is a highly heterogeneous and aggressive malignancy. Due to the absence of estrogen receptors and progesterone receptors and the lack of overexpression of human epidermal growth factor receptor 2, TNBC responds poorly to endocrine and targeted therapies. As a neoadjuvant therapy, chemotherapy is usually the only option for TNBC; however, chemotherapy may induce tumor resistance. The emergence of immunotherapy as an adjuvant therapy is expected to make up for the deficiency of chemotherapy. Most of the research on immunotherapies has been performed on advanced metastatic TNBC, which has provided significant clinical benefits. In the present review, possible immunotherapy targets and ongoing immunotherapy strategies were discussed. In addition, progress in research on immune checkpoint inhibitors in early TNBC was outlined.
| S-EPMC9256074 | biostudies-literature
Project description:Triple negative breast cancer (TNBC) represents the most malignant subtype of breast cancer, and yet our understanding about its unique biology remains elusive. We have conducted a comparative computational analysis of transcriptomic data of TNBC and non-TNBC (NTNBC) tissue samples from the TCGA database, focused on genes involved in neural functions. Our main discoveries are: (1) while both subtypes involve neural functions, TNBC has substantially more up-regulated neural genes than NTNBC, suggesting that TNBC is more complex than NTNBC; (2) non-neural functions related to cell-microenvironment interactions and intracellular damage processing are key inducers of the neural genes in both TNBC and NTNBC, but the inducer-responder relationships are different in the two cancer subtypes; (3) key neural functions such as neural crest formation are predicted to enhance adaptive immunity in TNBC while glia development, along with a few other neural functions, induce both innate and adaptive immunity in NTNBC. These results reveal key differences in the biology between the two cancer subtypes, particularly in terms of the roles that neural functions play. Our findings may open new doors for further investigation of the distinct biology of TNBC vs. NTNBC.
| S-EPMC7033128 | biostudies-literature
Project description:The efficacy of non-small cell lung cancer (NSCLC) has been obviously improved recent years, while the survival of small cell lung cancer (SCLC) patients remains inferior for limit treatment options. The incidence of SCLC accounts for 15% of the overall incidence of lung cancer, and it is characterized with high malignancy, rapid growth, early widespread metastasis, making it very difficult to treat. With the approval of immunotherapy for a variety of solid tumors including NSCLC, as a relatively immunogenic cancer species, relevant clinical researchs on SCLC are also underway and have made certain progress. More importantly, due to the existence of tumor heterogeneity, exploring relevant markers that can predict the efficacy of SCLC is essential for accurate therapy. This review describes the latest advances in SCLC immunotherapy and biomarkers related to the efficacy of immunotherapy.
| S-EPMC7118334 | biostudies-literature
Project description:BackgroundTreatment options for women presenting with triple negative breast cancer (TNBC) are limited due to the lack of a therapeutic target and as a result, are managed with standard chemotherapy such as paclitaxel (Taxol®). Following chemotherapy, the ideal tumour response is apoptotic cell death. Post-chemotherapy, cells can maintain viability by undergoing viable cellular responses such as cellular senescence, generating secretomes which can directly enhance the malignant phenotype.Scope of reviewHow tumour cells retain viability in response to chemotherapeutic engagement is discussed. In addition we discuss the implications of this retained tumour cell viability in the context of the development of recurrent and metastatic TNBC disease. Current adjuvant and neo-adjuvant treatments available and the novel potential therapies that are being researched are also reviewed.Major conclusionsCellular senescence and cytoprotective autophagy are potential mechanisms of chemoresistance in TNBC. These two non-apoptotic outcomes in response to chemotherapy are inextricably linked and are neglected outcomes of investigation in the chemotherapeutic arena. Cellular fate assessments may therefore have the potential to predict TNBC patient outcome.General significanceFocusing on the fact that cancer cells can bypass the desired cellular apoptotic response to chemotherapy through cellular senescence and cytoprotective autophagy will highlight the importance of targeting non-apoptotic survival pathways to enhance chemotherapeutic efficacy.
| S-EPMC4661576 | biostudies-literature
Project description:Triple-negative breast cancer (TNBC) accounts for 15-20% of all breast cancers and is characterized by an aggressive nature and a high rate of recurrence despite neoadjuvant and adjuvant chemotherapy. Although novel agents are constantly being introduced for the treatment of breast cancer, conventional cytotoxic chemotherapy based on anthracyclines and taxanes is the mainstay treatment option for TNBC. Based on CTNeoBC pooled analysis data, the achievement of pathologic CR (pCR) in TNBC is directly linked to improved survival outcomes. Therefore, the treatment paradigm for early TNBC has shifted to neoadjuvant treatment, and the escalation of neoadjuvant chemotherapy to improve the pCR rate and the addition of post-neoadjuvant chemotherapy to control the residual disease have been investigated. In this article, we review the current treatment landscape for early TNBC, from standard cytotoxic chemotherapy to recent data on immune checkpoint inhibitors, capecitabine, and olaparib.
| S-EPMC9962369 | biostudies-literature
Project description:Triple-negative breast cancer (TNBC) is a heterogeneous group of tumours in which chemotherapy, the current mainstay of systemic treatment, is often initially beneficial but with a high risk of relapse and metastasis. There is currently no means of predicting which TNBC will relapse. We tested the hypothesis that the biological properties of normal stem cells are re-activated in tumour metastasis and that, therefore, the activation of normal mammary stem cell-associated gene sets in primary TNBC would be highly prognostic for relapse and metastasis.Mammary basal stem and myoepithelial cells were isolated by flow cytometry and tested in low-dose transplant assays. Gene expression microarrays were used to establish expression profiles of the stem and myoepithelial populations; these were compared to each other and to our previously established mammary epithelial gene expression profiles. Stem cell genes were classified by Gene Ontology (GO) analysis and the expression of a subset analysed in the stem cell population at single cell resolution. Activation of stem cell genes was interrogated across different breast cancer cohorts and within specific subtypes and tested for clinical prognostic power.A set of 323 genes was identified that was expressed significantly more highly in the purified basal stem cells compared to all other cells of the mammary epithelium. A total of 109 out of 323 genes had been associated with stem cell features in at least one other study in addition to our own, providing further support for their involvement in the biology of this cell type. GO analysis demonstrated an enrichment of these genes for an association with cell migration, cytoskeletal regulation and tissue morphogenesis, consistent with a role in invasion and metastasis. Single cell resolution analysis showed that individual cells co-expressed both epithelial- and mesenchymal-associated genes/proteins. Most strikingly, we demonstrated that strong activity of this stem cell gene set in TNBCs identified those tumours most likely to rapidly progress to metastasis.Our findings support the hypothesis that the biological properties of normal stem cells are drivers of metastasis and that these properties can be used to stratify patients with a highly heterogeneous disease such as TNBC.
| S-EPMC4381533 | biostudies-literature
Project description:Triple-negative breast cancer (TNBC) has a significant clinical relevance of being associated with a shorter median time to relapse and death and does not respond to endocrine therapy or other available targeted agents. Increased aggressiveness of this tumor, as well as resistance to standard drug therapies, may be associated with the presence of stem cell populations within the tumor. Several stemness markers have been described for the various histological subtypes of breast cancer, such as CD44, CD24, CD133, ALDH1, and ABCG2. The role of these markers in breast cancer is not clear yet and above all there are conflicting opinions about their real prognostic value. To investigate the role of CSCs markers in TNBC cancerogenesis and tumor progression, we selected 160 TNBCs samples on which we detected protein expression of CD44, CD24, CD133, ALDH1, and ABCG2 by immunohistochemistry. Our results highlighted a real prognostic role only for CD44 in TNBCs. All other CSCs markers do not appear to be related to the survival of TNBC patients. In conclusion, despite the fact that the presence of the cancer stem cells in the tumor provides important information on its potential aggressiveness, today their detection by immunohistochemistry is not sufficient to confirm their role in carcinogenesis, because specific markers probably are not yet identified.
| S-EPMC4609334 | biostudies-literature
Project description:Triple negative breast cancer (TNBC) is characterized by the lack of estrogen and progesterone receptor expression and lacks HER2 overexpression or gene amplification. It accounts for 10-15% of incident breast cancers and carries the worst prognosis. TNBC is overrepresented among Black and pre-menopausal women and is associated with significant psychological and treatment-related burdens, including financial toxicity. Like other breast cancers, TNBC is biologically heterogeneous, leading to diverse clinical and epidemiological behaviors, however, unlike the other clinical subtypes, in TNBC we still lack tumor-specific targeted therapy. Early TNBC outcomes have improved due to the intensification of therapies, including improvements in polychemotherapy and the addition of immunotherapy. Future efforts are needed to identify targetable aberrations for specific drug therapy, prevent immune evasion, and increase social-economic support. Given that the name TNBC illustrates its lack of specifically targeted and effective therapy, we look forward to being able to retire the name in favor of a group of targetable entities within what is now called "TNBC".
| S-EPMC9392735 | biostudies-literature