scholarly journals Genomic Insights into Triple-Negative and HER2-Positive Breast Cancers Using Isogenic Model Systems

PLoS ONE ◽  
2013 ◽  
Vol 8 (9) ◽  
pp. e74993 ◽  
Author(s):  
Prakriti Mudvari ◽  
Kazufumi Ohshiro ◽  
Vasudha Nair ◽  
Anelia Horvath ◽  
Rakesh Kumar
Keyword(s):  
Triple Negative ◽  
Model Systems ◽  
Breast Cancers ◽  
Her2 Positive

scholarly journals Classical Cyclophosphamide, Methotrexate, and Fluorouracil Chemotherapy Is More Effective in Triple-Negative, Node-Negative Breast Cancer: Results From Two Randomized Trials of Adjuvant Chemoendocrine Therapy for Node-Negative Breast Cancer

2010 ◽  
Vol 28 (18) ◽  
pp. 2966-2973 ◽  
Author(s):  
Marco Colleoni ◽  
Bernard F. Cole ◽  
Giuseppe Viale ◽  
Meredith M. Regan ◽  
Karen N. Price ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Endocrine Therapy ◽  
Triple Negative ◽  
Alkylating Agents ◽  
Growth Factor Receptor ◽  
Breast Cancers ◽  
Her2 Positive ◽  
Node Negative ◽  
Tumor Subtypes ◽  
Node Negative Breast Cancer

Purpose Retrospective studies suggest that primary breast cancers lacking estrogen receptor (ER) and progesterone receptor (PR) and not overexpressing human epidermal growth factor receptor 2 (HER2; triple-negative tumors) are particularly sensitive to DNA-damaging chemotherapy with alkylating agents. Patients and Methods Patients enrolled in International Breast Cancer Study Group Trials VIII and IX with node-negative, operable breast cancer and centrally assessed ER, PR, and HER2 were included (n = 2,257). The trials compared three or six courses of adjuvant classical cyclophosphamide, methotrexate, and fluorouracil (CMF) with or without endocrine therapy versus endocrine therapy alone. We explored patterns of recurrence by treatment according to three immunohistochemically defined tumor subtypes: triple negative, HER2 positive and endocrine receptor absent, and endocrine receptor present. Results Patients with triple-negative tumors (303 patients; 13%) were significantly more likely to have tumors > 2 cm and grade 3 compared with those in the HER2-positive, endocrine receptor–absent, and endocrine receptor–present subtypes. No clear chemotherapy benefit was observed in endocrine receptor–present disease (hazard ratio [HR], 0.90; 95% CI, 0.74 to 1.11). A statistically significantly greater benefit for chemotherapy versus no chemotherapy was observed in triple-negative breast cancer (HR, 0.46; 95% CI, 0.29 to 0.73; interaction P = .009 v endocrine receptor–present disease). The magnitude of the chemotherapy effect was lower in HER2-positive endocrine receptor–absent disease (HR, 0.58; 95% CI, 0.29 to 1.17; interaction P = .24 v endocrine receptor–present disease). Conclusion The magnitude of benefit of CMF chemotherapy is largest in patients with triple-negative, node-negative breast cancer.

scholarly journals Identification of Long Noncoding RNAs as Predictors of Survival in Triple-Negative Breast Cancer Based on Network Analysis

2020 ◽  
Vol 2020 ◽  
pp. 1-15 ◽  
Author(s):  
Xiao-Xiao Li ◽  
Li-Juan Wang ◽  
Jie Hou ◽  
Hong-Yang Liu ◽  
Rui Wang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Network Analysis ◽  
Molecular Mechanisms ◽  
Triple Negative ◽  
Noncoding Rnas ◽  
Long Noncoding Rnas ◽  
Breast Cancers ◽  
Luminal A ◽  
Her2 Positive ◽  
Cancer Subtypes

Breast cancer is the most common cancer observed in adult females, worldwide. Due to the heterogeneity and varied molecular subtypes of breast cancer, the molecular mechanisms underlying carcinogenesis in different subtypes of breast cancer are distinct. Recently, long noncoding RNAs (lncRNAs) have been shown to be oncogenic or play important roles in cancer suppression and are used as biomarkers for diagnosis and therapy. In this study, we identified 134 lncRNAs and 6,414 coding genes were differentially expressed in triple-negative (TN), human epidermal growth factor receptor 2- (HER2-) positive, luminal A-positive, and luminal B-positive breast cancer. Of these, 37 lncRNAs were found to be dysregulated in all four subtypes of breast cancers. Subtypes of breast cancer special modules and lncRNA-mRNA interaction networks were constructed through weighted gene coexpression network analysis (WGCNA). Survival analysis of another public datasets was used to verify the identified lncRNAs exhibiting potential indicative roles in TN prognosis. Results from heat map analysis of the identified lncRNAs revealed that five blocks were significantly displayed. High expressions of lncRNAs, including LINC00911, CSMD2-AS1, LINC01192, SNHG19, DSCAM-AS1, PCAT4, ACVR28-AS1, and CNTFR-AS1, and low expressions of THAP9-AS1, MALAT1, TUG1, CAHM, FAM2011, NNT-AS1, COX10-AS1, and RPARP-AS1 were associated with low survival possibility in TN breast cancers. This study provides novel lncRNAs as potential biomarkers for the therapeutic and prognostic classification of different breast cancer subtypes.

Adjuvant chemotherapy in T1a/bN0 HER2-positive or triple-negative breast cancers: Application and outcomes

The Breast ◽  
2013 ◽  
Vol 22 (5) ◽  
pp. 793-798 ◽  
Author(s):  
Yazan Migdady ◽  
Bachir J. Sakr ◽  
William M. Sikov ◽  
Adam J. Olszewski
Keyword(s):  
Adjuvant Chemotherapy ◽  
Triple Negative ◽  
Breast Cancers ◽  
Her2 Positive

scholarly journals Simultaneous Multi-Organ Metastases from Chemo-Resistant Triple-Negative Breast Cancer Are Prevented by Interfering with WNT-Signaling

Cancers ◽  
2019 ◽  
Vol 11 (12) ◽  
pp. 2039 ◽  
Author(s):  
Iram Fatima ◽  
Ikbale El-Ayachi ◽  
Hilaire C. Playa ◽  
Jackelyn A. Alva-Ornelas ◽  
Aysha B. Khalid ◽  
...  
Keyword(s):  
Cell Lines ◽  
Triple Negative ◽  
De Novo ◽  
Tumor Model ◽  
Model Systems ◽  
Breast Cancers ◽  
Primary Tumors ◽  
Multiple Organs

Triple-negative breast cancers (TNBCs), which lack specific targeted therapy options, evolve into highly chemo-resistant tumors that metastasize to multiple organs simultaneously. We have previously shown that TNBCs maintain an activated WNT10B-driven network that drives metastasis. Pharmacologic inhibition by ICG-001 decreases β-catenin-mediated proliferation of multiple TNBC cell lines and TNBC patient-derived xenograft (PDX)-derived cell lines. In vitro, ICG-001 was effective in combination with the conventional cytotoxic chemotherapeutics, cisplatin and doxorubicin, to decrease the proliferation of MDA-MB-231 cells. In contrast, in TNBC PDX-derived cells doxorubicin plus ICG-001 was synergistic, while pairing with cisplatin was not as effective. Mechanistically, cytotoxicity induced by doxorubicin, but not cisplatin, with ICG-001 was associated with increased cleavage of PARP-1 in the PDX cells only. In vivo, MDA-MB-231 and TNBC PDX orthotopic primary tumors initiated de novo simultaneous multi-organ metastases, including bone metastases. WNT monotherapy blocked multi-organ metastases as measured by luciferase imaging and histology. The loss of expression of the WNT10B/β-catenin direct targets HMGA2, EZH2, AXIN2, MYC, PCNA, CCND1, transcriptionally active β-catenin, SNAIL and vimentin both in vitro and in vivo in the primary tumors mechanistically explains loss of multi-organ metastases. WNT monotherapy induced VEGFA expression in both tumor model systems, whereas increased CD31 was observed only in the MDA-MB-231 tumors. Moreover, WNT-inhibition sensitized the anticancer response of the TNBC PDX model to doxorubicin, preventing simultaneous metastases to the liver and ovaries, as well as to bone. Our data demonstrate that WNT-inhibition sensitizes TNBC to anthracyclines and treats multi-organ metastases of TNBC.

Changing frameworks in treatment sequencing of triple-negative and HER2-positive, early-stage breast cancers

2019 ◽  
Vol 20 (7) ◽  
pp. e390-e396 ◽  
Author(s):  
Lajos Pusztai ◽  
Julia Foldi ◽  
Arjun Dhawan ◽  
Michael P DiGiovanna ◽  
Eleftherios P Mamounas
Keyword(s):  
Triple Negative ◽  
Early Stage ◽  
Breast Cancers ◽  
Her2 Positive ◽  
Treatment Sequencing

scholarly journals Circulating miRNAs in HER2-Positive and Triple Negative Breast Cancers: Potential Biomarkers and Therapeutic Targets

2020 ◽  
Vol 21 (18) ◽  
pp. 6750
Author(s):  
Ishita Gupta ◽  
Balsam Rizeq ◽  
Semir Vranic ◽  
Ala-Eddin Al Moustafa ◽  
Halema Al Farsi
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Triple Negative ◽  
Therapeutic Targets ◽  
Breast Cancers ◽  
Breast Cancer Patients ◽  
Circulating Mirnas ◽  
Her2 Positive ◽  
Cancer Disease ◽  
Estrogen Receptor Negative

Breast cancer is one of the most prevalent diseases among women worldwide and is highly associated with cancer-related mortality. Of the four major molecular subtypes, HER2-positive and triple-negative breast cancer (TNBC) comprise more than 30% of all breast cancers. While the HER2-positive subtype lacks estrogen and progesterone receptors and overexpresses HER2, the TNBC subtype lacks estrogen, progesterone and HER2 receptors. Although advances in molecular biology and genetics have substantially ameliorated breast cancer disease management, targeted therapies for the treatment of estrogen-receptor negative breast cancer patients are still restricted, particularly for TNBC. On the other hand, it has been demonstrated that microRNAs, miRNAs or small non-coding RNAs that regulate gene expression are involved in diverse biological processes, including carcinogenesis. Moreover, circulating miRNAs in serum/plasma are among the most promising diagnostic/therapeutic tools as they are stable and relatively easy to quantify. Various circulating miRNAs have been identified in several human cancers including specific breast cancer subtypes. This review aims to discuss the role of circulating miRNAs as potential diagnostic and prognostic biomarkers as well as therapeutic targets for estrogen-receptor negative breast cancers, HER2+ and triple negative.

scholarly journals Targeting Replicative Stress and DNA Repair by Combining PARP and Wee1 Kinase Inhibitors Is Synergistic in Triple Negative Breast Cancers with Cyclin E or BRCA1 Alteration

Cancers ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1656
Author(s):  
Xian Chen ◽  
Dong Yang ◽  
Jason P. W. Carey ◽  
Cansu Karakas ◽  
Constance Albarracin ◽  
...  
Keyword(s):  
Dna Repair ◽  
Combination Treatment ◽  
Triple Negative ◽  
Kinase Inhibitor ◽  
Cyclin E ◽  
Parp Inhibitor ◽  
Model Systems ◽  
In Vivo Model ◽  
Breast Cancers ◽  
Replicative Stress

The identification of biomarker-driven targeted therapies for patients with triple negative breast cancer (TNBC) remains a major clinical challenge, due to a lack of specific targets. Here, we show that cyclin E, a major regulator of G1 to S transition, is deregulated in TNBC and is associated with mutations in DNA repair genes (e.g., BRCA1/2). Breast cancers with high levels of cyclin E not only have a higher prevalence of BRCA1/2 mutations, but also are associated with the worst outcomes. Using several in vitro and in vivo model systems, we show that TNBCs that harbor either mutations in BRCA1/2 or overexpression of cyclin E are very sensitive to the growth inhibitory effects of AZD-1775 (Wee 1 kinase inhibitor) when used in combination with MK-4837 (PARP inhibitor). Combination treatment of TNBC cell lines with these two agents results in synergistic cell killing due to induction of replicative stress, downregulation of DNA repair and cytokinesis failure that results in increased apoptosis. These findings highlight the potential clinical application of using cyclin E and BRCA mutations as biomarkers to select only those patients with the highest replicative stress properties that may benefit from combination treatment with Wee 1 kinase and PARP inhibitors.

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