scholarly journals Mapping Intellectual Structures and Research Hotspots of Triple Negative Breast Cancer: A Bibliometric Analysis

2022 ◽  
Vol 11 ◽  
Author(s):  
Kai-jun Hao ◽  
Xiao Jia ◽  
Wen-ting Dai ◽  
Ze-min Huo ◽  
Hua-qiang Zhang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Breast Cancer Subtype ◽  
Parp Inhibitor ◽  
Cancer Center ◽  
Burst Detection ◽  
Scientific Publications ◽  
Tumor Cell Migration ◽  
Research Hotspots

BackgroundTriple negative breast cancer (TNBC) is a highly heterogeneous breast cancer subtype with a poor prognosis due to its extremely aggressive nature and lack of effective treatment options. This study aims to summarize the current hotspots of TNBC research and evaluate the TNBC research trends, both qualitatively and quantitatively.MethodsScientific publications of TNBC-related studies from January 1, 2010 to October 17, 2020 were obtained from the Web of Science database. The BICOMB software was used to obtain the high-frequency keywords layout. The gCLUTO was used to produce a biclustering analysis on the binary matrix of word-paper. The co-occurrence and collaboration analysis between authors, countries, institutions, and keywords were performed by VOSviewer software. Keyword burst detection was performed by CiteSpace.ResultsA total of 12,429 articles related to TNBC were identified. During 2010-2020, the most productive country/region and institution in TNBC field was the USA and The University of Texas MD Anderson Cancer Center, respectively. Cancer Research, Journal of Clinical Oncology, and Annals of Oncology were the first three periodicals with maximum publications in TNBC research. Eight research hotspots of TNBC were identified by co-word analysis. In the core hotspots, research on neoadjuvant chemotherapy, paclitaxel therapy, and molecular typing of TNBC is relatively mature. Research on immunotherapy and PARP inhibitor for TNBC is not yet mature but is the current focus of this field. Burst detection of keywords showed that studies on TNBC proteins and receptors, immunotherapy, target, and tumor cell migration showed bursts in recent three years.ConclusionThe current study revealed that TNBC studies are growing. Attention should be paid to the latest hotspots, such as immunotherapy, PARP inhibitors, target, and TNBC proteins and receptors.

scholarly journals Breast Cancer: 2021 ASCO Annual Meeting Highlights for the Advanced Practitioner

2021 ◽  
Vol 12 (6) ◽  
Author(s):  
Sheeba Cantanelli, MPAS, PA-C
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Early Stage ◽  
Parp Inhibitor ◽  
Metastatic Breast ◽  
Comprehensive Cancer Center ◽  
Cancer Center ◽  
Vitamin D Levels ◽  
The Impact

Sheeba Cantanelli, MPAS, PA-C, of UT Southwestern Medical Center, Simmons Comprehensive Cancer Center, discusses results from studies evaluating adjuvant therapy with a PARP inhibitor in BRCA-mutated HER2-negative metastatic breast cancer; immunotherapy in the treatment of early-stage triple-negative breast cancer; adjuvant capecitabine after neoadjuvant chemotherapy in triple-negative breast cancer; the addition of palbociclib to fulvestrant in HR-positive, HER2-negative advanced breast cancer; and the impact of vitamin D levels on outcomes. Reporting is provided by The ASCO Post.

scholarly journals Effect of Oxaliplatin, Olaparib and LY294002 in Combination on Triple-Negative Breast Cancer Cells

2021 ◽  
Vol 22 (4) ◽  
pp. 2056
Author(s):  
Kitti Andreidesz ◽  
Balazs Koszegi ◽  
Dominika Kovacs ◽  
Viola Bagone Vantus ◽  
Ferenc Gallyas ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Parp Inhibitor ◽  
Combined Treatment ◽  
Parp Inhibition ◽  
Akt Pathway ◽  
Platinum Compound ◽  
Mcf7 Cells ◽  
Cancer Line

Triple-negative breast cancer (TNBC) has a poor prognosis as the therapy has several limitations, most importantly, treatment resistance. In this study we examined the different responses of triple-negative breast cancer line MDA-MB-231 and hormone receptor-positive breast cancer line MCF7 to a combined treatment including olaparib, a poly-(ADP ribose) polymerase (PARP) inhibitor, oxaliplatin, a third-generation platinum compound and LY294002, an Akt pathway inhibitor. We applied the drugs in a single, therapeutically relevant concentration individually and in all possible combinations, and we assessed the viability, type of cell death, reactive oxygen species production, cell-cycle phases, colony formation and invasive growth. In agreement with the literature, the MDA-MB-231 cells were more treatment resistant than the MCF7 cells. However, and in contrast with the findings of others, we detected no synergistic effect between olaparib and oxaliplatin, and we found that the Akt pathway inhibitor augmented the cytostatic properties of the platinum compound and/or prevented the cytoprotective effects of PARP inhibition. Our results suggest that, at therapeutically relevant concentrations, the cytotoxicity of the platinum compound dominated over that of the PARP inhibitor and the PI3K inhibitor, even though a regression-based model could have indicated an overall synergy at lower and/or higher concentrations.

scholarly journals Blocking Fra-1 sensitizes triple-negative breast cancer to PARP inhibitor

2021 ◽  
Author(s):  
Dandan Song ◽  
Huan He ◽  
Indranil Sinha ◽  
Linnea Hases ◽  
Feifei Yan ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Parp Inhibitor

321 Phase I clinical trial assessing the combination of systemic chemokine modulatory regimen targeting TLR3 with neoadjuvant chemotherapy in triple negative breast cancer

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A347-A347
Author(s):  
Shipra Gandhi ◽  
Mateusz Opyrchal ◽  
Cayla Ford ◽  
Victoria Fitzpatrick ◽  
Melissa Grimm ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Phase I ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Early Stage ◽  
Standard Dose ◽  
Surrogate Marker ◽  
Comprehensive Cancer Center ◽  
Cancer Center

BackgroundNeoadjuvant chemotherapy (NAC) with taxanes is the standard of care in triple negative breast cancer (TNBC). Intratumoral prevalence of CD8+ cytotoxic T-lymphocytes (CTLs) is associated with an improvement in relapse-free survival (RFS) and overall survival (OS), while regulatory T-cells (Treg) and myeloid derived suppressor cells (MDSC) are associated with poor survival. Higher ratio of CTL/Treg is associated with higher probability of obtaining pathological complete response (pCR), a surrogate marker for RFS. Intratumoral production of CCL5, CXCL9, CXCL10 and CXCL11 is critical for local infiltration with CTLs, while CCL22 is responsible for Treg attraction. Previous studies have shown that CXCL9 expression in the pre-treatment breast tissue is associated with a three-fold higher rate of achieving pCR. Our preclinical data show that Chemokine modulating (CKM) regimen, combining rintatolimod (TLR3 agonist), interferon (IFN)-α2b, and celecoxib (COX-2 inhibitor) increases CTL-attracting, and decreases MDSC-, Treg-favoring chemokines, increasing CTL/Treg ratio in tumor microenvironment, with preferential tumor tissue activation than adjacent healthy tissues. We hypothesize that the combination of CKM with paclitaxel will result in infiltration of TNBC with CTLs, and along with doxorubicin/cyclophosphamide (AC), result in higher pCR, translating into improved RFS and OS.MethodsIn this phase I study NCT04081389, eligibility includes age ≥18 years, confirmed resectable TNBC, radiographically measurable disease ≥1 cm, ECOG PS ≤ 2, adequate organ and marrow function. Patients with autoimmune disease, serious mood disorders, invasive carcinoma within 3 years, history of peptic ulcers or hypersensitivity to NSAIDs will be excluded. We plan to treat three patients with early stage TNBC with paclitaxel 80 mg/m2 IV weekly for 12 weeks, rintatolimod 200 mg IV, celecoxib 200 mg oral twice daily, and accelerated titration of IFN-α2b at doses 0, 5, or 10 million units (MU)/m2 [Dose Levels (DL) 1, 2 and 3 respectively] on days 1–3 (no intra-patient dose escalation) in weeks 1–3. Dose-limiting toxicity (DLT) is defined as grade 3 or higher toxicities within the first 3 weeks. Any DLT will mandate recruitment per the 3+3 model. If no DLT, three patients will be enrolled at DL 4 at 20 MU/m2 IFN- α2b. This will be followed by standard dose-dense AC, and then surgery. The primary endpoint is safety and tolerability of combination and to identify the appropriate DL of CKM and paclitaxel for extended efficacy study. The secondary endpoints include investigation of efficacy (pCR and breast MRI response), along with RFS and OS. Intratumoral biomarkers will be analyzed in an exploratory manner.ResultsN/AConclusionsN/ATrial RegistrationNCT04081389Ethics ApprovalThe study was approved by Roswell Park Comprehensive Cancer Center Institution’s Ethics Board, approval number I-73718.

Abstract 1066: Pre-clinical combination of a PARP inhibitor, talazoparib, and carboplatin in triple-negative breast cancer

2021 ◽  
Author(s):  
Alexia Cotte ◽  
Michèle Beniey ◽  
Takrima Haque ◽  
Nelly Béchir ◽  
Audrey Hubert ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Parp Inhibitor

scholarly journals 614 Investigating immune mediated mechanisms of PARPi resistance in BRCA1-associated triple negative breast cancer (TNBC)

2021 ◽  
Vol 9 (Suppl 3) ◽  
pp. A644-A644
Author(s):  
Anita Mehta ◽  
Madeline Townsend ◽  
Madisson Oliwa ◽  
Patrice Lee ◽  
Nicholas Saccomano ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Flow Cytometry ◽  
Immune Response ◽  
T Cell ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Parp Inhibitor ◽  
Triple Combination ◽  
Tumor Clearance ◽  
Sting Pathway

BackgroundPoly(ADP-ribose) polymerase inhibitors (PARPi) have improved the outcomes of BRCA-associated breast cancer; however, treatment responses are often not durable. Our preclinical studies demonstrated that PARPi activates the cGAS/STING pathway and recruitment of anti-tumor CD8+ T-cells that are required for tumor clearance [1]. These studies contributed to development of clinical trials testing PARPi plus immune checkpoint blockade (ICB). Unfortunately, early phase trials of PARPi + ICB have not yet suggested efficacy will be superior to PARPi monotherapy. Lack of demonstrated clinical synergy between PARPi + ICB underscores the need to study the tumor microenvironment (TME) during PARPi therapy to identify optimal strategies to enhance T-cell activation. We recently showed that PARPi induces CSF-1R+ suppressive tumor associated macrophages (TAMs) that restrict antitumor immune responses, contributing to PARPi resistance [2]. Removing TAMs with anti-CSF-1R therapy in combination with PARPi significantly enhanced overall survival (OS) compared to PARPi monotherapy in preclinical models [2]. Here, we investigate how modulating TAMs can enhance PARPi + ICB.MethodsMice bearing BRCA1-deficient TNBC (K14-Cre;Brca1f/f;p53f/f) tumors were treated for 98 days with PARPi (Talazoparib) ± small molecule inhibitor of CSF-1R (ARRAY-382; CSF-1Ri) ± anti-PD-1 and then followed for survival. Flow cytometry was employed to elucidate changes in the TME after treatment.ResultsPARPi conferred a significant survival advantage over vehicle treated mice (median OS 33 v. 14 days; p=0.0034) and 2/8 PARPi-treated mice experienced complete tumor clearance at day 98. PARPi + CSF-1Ri treated mice (median OS 140 days) remarkably cleared 7/10 tumors by day 98. The addition of anti-PD-1 to PARPi did not enhance OS compared to PARPi monotherapy. The triple combination of anti-PD-1 + PARPi + CSF-1Ri has not yet significantly enhanced the median OS compared to PARPi + CSF-1Ri (ongoing; 168 v. 140 days); nor did it increase clearance of tumor by day 98 (7/10). However, the triple combination led to superior long term tumor clearance. At day 161 the triple combination exhibited 5/10 tumor free mice compared to 2/10 treated with PARPi + CSF-1Ri. To elucidate how CSR-1Ri enhanced PARPi + ICB responses, flow cytometry was performed and revealed increased expression of the co-stimulatory molecule CD80, reduced tissue resident macrophages (CX3CR1+) and lower CSF-1R expression compared to PARPi + ICB.ConclusionsThese data suggest that targeting immunosuppressive macrophages may induce a favorable anti-tumor immune response and enhance responses to PARPi plus ICB. We are currently evaluating the adaptive immune response in this context.ReferencesPantelidou, C., et al., PARP inhibitor efficacy depends on CD8+ T cell recruitment via intratumoral STING pathway activation in BRCA-deficient models of triple-negative breast cancer. Cancer Discovery, 2019: p. CD-18-1218.Mehta, A.K., et al., Targeting immunosuppressive macrophages overcomes PARP inhibitor resistance in BRCA1-associated triple-negative breast cancer. Nat Cancer, 2021. 2(1): p. 66–82.

scholarly journals Influence of Germline BRCA Genotype on the Survival of Patients with Triple-Negative Breast Cancer

2021 ◽  
Vol 1 (3) ◽  
pp. 140-147
Author(s):  
Cynthia Villarreal-Garza ◽  
Ana S. Ferrigno ◽  
Alejandro Aranda-Gutierrez ◽  
Paul H. Frankel ◽  
Nora H. Ruel ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Point Mutations ◽  
Treatment Resistance ◽  
Cancer Center ◽  
Breast Cancers ◽  
Entire Cohort ◽  
Pathogenic Variants ◽  
Mutational Status

The presence of BRCA pathogenic variants (PV) in triple-negative breast cancer (TNBC) is associated with a distinctive genomic profile that makes the tumor particularly susceptible to DNA-damaging treatments. However, patients with BRCA PVs can develop treatment resistance through the appearance of reversion mutations and restored BRCA expression. As copy-number variants (CNV) could be less susceptible to reversion mutations than point mutations, we hypothesize that carriers of BRCA CNVs may have improved survival after treatment compared with carriers of other BRCA PVs or BRCA wild-type. Women diagnosed with stage I–III TNBC at ≤50 years at a cancer center in Mexico City were screened for BRCA PVs using a recurrent PV assay (HISPANEL; 77% sensitivity). Recurrence-free survival (RFS) and overall survival (OS) were compared according to the mutational status. Among 180 women, 17 (9%) were carriers of BRCA1 ex9–12del CNVs and 26 (14%) of other BRCA PVs. RFS at ten years for the whole cohort was 79.2% [95% confidence interval (CI), 72.3–84.6], with no significant differences according to mutational status. 10-year OS for the entire cohort was 85.3% (95% CI, 78.7–90.0), with BRCA CNV carriers demonstrating numerically superior OS rates other PV carriers and noncarriers (100% vs. 78.6% and 84.7%; log-rank P = 0.037 and P = 0.051, respectively). This study suggests that BRCA1 ex9–12del CNV carriers with TNBC may have a better OS, and supports the hypothesis that the genotype of BRCA PVs may influence survival by limiting treatment resistance mediated by reversion mutations among CNV carriers. Significance: Large CNV BRCA carriers in a cohort of young Mexican patients with TNBC had superior OS rates than carriers of other BRCA pathogenic variants (i.e., small indels or point mutations). We hypothesize that this is due to the resistance of CNVs to reversion mutations mediating resistance to therapy. If validated, these findings have important prognostic and clinical treatment implications for BRCA-associated breast cancers.

scholarly journals Synergistic Interaction Betweem Olaparib, a Parp Inhibitor, and Cytotoxic Agent in Triple Negative Breast Cancer

2013 ◽  
Vol 24 ◽  
pp. ix59 ◽  
Author(s):  
J. Hashimoto ◽  
Y. Kitamura ◽  
Y. Takashima ◽  
Y. Kodera ◽  
S. Shimma ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Parp Inhibitor ◽  
Synergistic Interaction ◽  
Cytotoxic Agent

scholarly journals Berberine Impairs the Survival of Triple Negative Breast Cancer Cells: Cellular and Molecular Analyses

Molecules ◽  
2020 ◽  
Vol 25 (3) ◽  
pp. 506 ◽  
Author(s):  
Lamyae El Khalki ◽  
Virginie Maire ◽  
Thierry Dubois ◽  
Abdelmajid Zyad
Keyword(s):  
Breast Cancer ◽  
Cell Lines ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Breast Cancer Subtype ◽  
Potential Candidate ◽  
Tnbc Cell ◽  
Normal Human Breast ◽  
Good Potential ◽  
Breast Cells

Triple negative breast cancer (TNBC) is an aggressive breast cancer subtype. Non-available targeted therapy for TNBC represents its biggest treatment challenge. Thus, finding new promising effective drugs is urgently needed. In the present study, we investigated how berberine, a natural isoquinoline, impairs the survival of TNBC cells in both cellular and molecular levels. Our experimental model was based on the use of eight TNBC cell lines: MDA-MB-468, MDA-MB-231, HCC70, HCC38, HCC1937, HCC1143, BT-20, and BT-549. Berberine was cytotoxic against all treated TNBC cell lines. The most sensitive cell lines were HCC70 (IC50 = 0.19 µM), BT-20 (IC50 = 0.23 µM) and MDA-MB-468 (IC50 = 0.48 µM). Using flow cytometry techniques, berberine, at 0.5 and 1 µM for 120 and 144 h, not only induced cell cycle arrest, at G1 and/or G2/M phases, but it also triggered significant apoptosis. At the molecular level, these results are consistent with the expression of their related proteins using Western blot assays. Interestingly, while berberine was cytotoxic against TNBC cells, it had no effect on the viability of normal human breast cells MCF10A cultured in a 3D matrigel model. These results suggest that berberine may be a good potential candidate for TNBC drug development.

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