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https://www.readbyqxmd.com/read/28650678/an-integrative-approach-for-identifying-network-biomarkers-of-breast-cancer-subtypes-using-genomic-interactomic-and-transcriptomic-data
#1
Forough Firoozbakht, Iman Rezaeian, Michele D'agnillo, Lisa Porter, Luis Rueda, Alioune Ngom
Breast cancer is a complex disease that can be classified into at least 10 different molecular subtypes. Appropriate diagnosis of specific subtypes is critical for ensuring the best possible patient treatment and response to therapy. Current computational methods for determining the subtypes are based on identifying differentially expressed genes (i.e., biomarkers) that can best discriminate the subtypes. Such approaches, however, are known to be unreliable since they yield different biomarker sets when applied to data sets from different studies...
June 26, 2017: Journal of Computational Biology: a Journal of Computational Molecular Cell Biology
https://www.readbyqxmd.com/read/28650484/insertional-mutagenesis-identifies-drivers-of-a-novel-oncogenic-pathway-in-invasive-lobular-breast-carcinoma
#2
Sjors M Kas, Julian R de Ruiter, Koen Schipper, Stefano Annunziato, Eva Schut, Sjoerd Klarenbeek, Anne Paulien Drenth, Eline van der Burg, Christiaan Klijn, Jelle J Ten Hoeve, David J Adams, Marco J Koudijs, Jelle Wesseling, Micha Nethe, Lodewyk F A Wessels, Jos Jonkers
Invasive lobular carcinoma (ILC) is the second most common breast cancer subtype and accounts for 8-14% of all cases. Although the majority of human ILCs are characterized by the functional loss of E-cadherin (encoded by CDH1), inactivation of Cdh1 does not predispose mice to develop mammary tumors, implying that mutations in additional genes are required for ILC formation in mice. To identify these genes, we performed an insertional mutagenesis screen using the Sleeping Beauty transposon system in mice with mammary-specific inactivation of Cdh1...
June 26, 2017: Nature Genetics
https://www.readbyqxmd.com/read/28650466/ror2-mediated-alternative-wnt-signaling-regulates-cell-fate-and-adhesion-during-mammary-tumor-progression
#3
K Roarty, A D Pfefferle, C J Creighton, C M Perou, J M Rosen
Cellular heterogeneity is a common feature in breast cancer, yet an understanding of the coexistence and regulation of various tumor cell subpopulations remains a significant challenge in cancer biology. In the current study, we approached tumor cell heterogeneity from the perspective of Wnt pathway biology to address how different modes of Wnt signaling shape the behaviors of diverse cell populations within a heterogeneous tumor landscape. Using a syngeneic TP53-null mouse model of breast cancer, we identified distinctions in the topology of canonical Wnt β-catenin-dependent signaling activity and non-canonical β-catenin-independent Ror2-mediated Wnt signaling across subtypes and within tumor cell subpopulations in vivo...
June 26, 2017: Oncogene
https://www.readbyqxmd.com/read/28649742/genotranscriptomic-meta-analysis-of-the-chd-family-chromatin-remodelers-in-human-cancers-initial-evidence-of-an-oncogenic-role-for-chd7
#4
Xiaofang Chu, Xuhui Guo, Yuanyuan Jiang, Huimei Yu, Lanxin Liu, Wenqi Shan, Zeng-Quan Yang
Chromodomain helicase DNA binding proteins (CHD) are characterized by N-terminal tandem chromodomains and a central ATP-dependent helicase domain. CHDs govern the cellular machinery's access to DNA, thereby playing critical roles in various cellular processes including transcription, proliferation, and DNA damage repair. Accumulating evidence demonstrates that mutation and dysregulation of CHDs are implicated in the pathogenesis of developmental disorders and cancer. However, we know little about genomic and transcriptomic alterations and the clinical significance of most CHDs in human cancer...
June 26, 2017: Molecular Oncology
https://www.readbyqxmd.com/read/28649649/patterns-of-cell-cycle-checkpoint-deregulation-associated-with-intrinsic-molecular-subtypes-of-human-breast-cancer-cells
#5
Jacquelyn J Bower, Leah D Vance, Matthew Psioda, Stephanie L Smith-Roe, Dennis A Simpson, Joseph G Ibrahim, Katherine A Hoadley, Charles M Perou, William K Kaufmann
Genomic instability is a hallmark of breast cancer, contributes to tumor heterogeneity, and influences chemotherapy resistance. Although Gap 2 and mitotic checkpoints are thought to prevent genomic instability, the role of these checkpoints in breast cancer is poorly understood. Here, we assess the Gap 2 and mitotic checkpoint functions of 24 breast cancer and immortalized mammary epithelial cell lines representing four of the six intrinsic molecular subtypes of breast cancer. We found that patterns of cell cycle checkpoint deregulation were associated with the intrinsic molecular subtype of breast cancer cell lines...
2017: NPJ Breast Cancer
https://www.readbyqxmd.com/read/28649648/dramatic-response-of-metaplastic-breast-cancer-to-chemo-immunotherapy
#6
Sylvia Adams
Frequent overexpression of programmed death-ligand 1 has recently been demonstrated in metaplastic breast cancer, which is a rare breast cancer subtype with limited treatment options. This report describes the clinical course of a patient with metastatic metaplastic breast cancer who had a remarkable response to anti-programmed death-1 therapy with pembrolizumab in combination with nab-paclitaxel. Tissue correlates are presented including tumor-infiltrating lymphocytes and high-programmed death-ligand 1 expression in the tumor...
2017: NPJ Breast Cancer
https://www.readbyqxmd.com/read/28649647/moonshots-and-metastatic-disease-the-need-for-a-multi-faceted-approach-when-studying-atypical-responses
#7
REVIEW
Kristine De La Torre, Elly Cohen, Anne Loeser, Marc Hurlbert
Clinical research generally focuses on results involving a statistical mean with little attention in trial design to patients who respond considerably better or worse than average. Exploring the reasons underlying an "atypical response" will increase understanding of the mechanisms involved in cancer progression and treatment resistance, accelerate biomarker identification, and improve precision medicine by allowing clinicians to prospectively select optimal treatments. Based on our review, we suggest two ways to move this field forward...
2017: NPJ Breast Cancer
https://www.readbyqxmd.com/read/28649644/constitutional-variants-are-not-associated-with-her2-positive-breast-cancer-results-from-the-signal-phare-clinical-cohort
#8
Xavier Pivot, Gilles Romieu, Pierre Fumoleau, Maria Rios, Hervé Bonnefoi, Thomas Bachelot, Patrick Soulié, Christelle Jouannaud, Hugues Bourgeois, Thierry Petit, Isabelle Tennevet, David Assouline, Marie-Christine Mathieu, Jean-Philippe Jacquin, Sandrine Lavau-Denes, Ariane Darut-Jouve, Jean-Marc Ferrero, Carole Tarpin, Christelle Lévy, Valérie Delecroix, Véronique Trillet-Lenoir, Oana Cojocarasu, Jérôme Meunier, Jean-Yves Pierga, Cécile Agostini, Pierre Kerbrat, Céline Faure-Mercier, Hélène Blanché, Mourad Sahbatou, Anne Boland, Delphine Bacq, Céline Besse, Fabien Calvo, Alexia Renaud, Jean-François Deleuze, Iris Pauporté, Gilles Thomas, David G Cox
Human epidermal growth factor receptor 2-positive breast cancer is a subtype of interest regarding its outcome and the impressive impact of human epidermal growth factor receptor 2 targeted therapy. Constitutional variants may be involved in the aetiology of human epidermal growth factor receptor 2-positive breast cancer, and we propose a case-case study to test the hypothesis that single nucleotide polymorphisms may be associated with human epidermal growth factor receptor 2 status. A Genome-Wide Association Study was used in a cohort of 9836 patients from the SIGNAL/PHARE study (NCT00381901-RECF1098)...
2017: NPJ Breast Cancer
https://www.readbyqxmd.com/read/28649032/a-standard-mastectomy-should-not-be-the-only-recommended-breast-surgical-treatment-for-non-metastatic-inflammatory-breast-cancer-a-large-population-based-study-in-the-surveillance-epidemiology-and-end-results-database-18
#9
Hongliang Chen, Kejin Wu, Maoli Wang, Fuwen Wang, Mingdi Zhang, Peng Zhang
BACKGROUND: Standard mastectomy has long been the recommended breast surgical treatment for non-metastatic inflammatory breast cancer (IBC). The objective of this population-based study was to evaluate the significance of various breast surgical treatments for this highly aggressive subtype. METHODS: The Surveillance, Epidemiology, and End Results program registry was searched to identify women with non-metastatic IBC receiving standard treatment including breast surgery, radiation therapy and chemotherapy diagnosed between 1998 and 2013...
June 22, 2017: Breast: Official Journal of the European Society of Mastology
https://www.readbyqxmd.com/read/28647608/a-route-based-pathway-analysis-framework-integrating-mutation-information-and-gene-expression-data
#10
Yue Zhao, Tham H Hoang, Pujan Joshi, Seung-Hyun Hong, Charles Giardina, Dong-Guk Shin
We propose a new way of analyzing biological pathways in which the analysis combines both transcriptome data and mutation information and uses the outcome to identify "routes" of aberrant pathways potentially responsible for the etiology of disease. Each pathway route is encoded as a Bayesian Network which is initialized with a sequence of conditional probabilities which are designed to encode directionality of regulatory relationships encoded in the pathways, i.e. activation and inhibition relationships. First, we demonstrate the effectiveness of our model through simulation in which the model was able to easily separate Test samples from Control samples using fictitiously perturbed pathway routes...
June 21, 2017: Methods: a Companion to Methods in Enzymology
https://www.readbyqxmd.com/read/28646722/radiation-therapy-utilization-and-outcomes-for-older-women-with-breast-cancer-impact-of-molecular-subtype-and-tumor-grade
#11
Waqar Haque, Denley Ming Kee Yuan, Vivek Verma, E Brian Butler, Bin S Teh, Lee Wiederhold, Sandra Hatch
BACKGROUND: Radiation therapy (RT) utilization for elderly women with respect to human epidermal growth factor receptor 2 (HER2) receptor status has not been evaluated. Our purpose was to determine differences in RT utilization and breast cancer specific survival (BCSS) for elderly breast cancer patients with distinct molecular biomarkers. METHODS: The Surveillance, Epidemiology, and End Results database was queried for women ≥70 years of age diagnosed with T1N0M0 breast cancer between 2010 and 2013 receiving breast conservation...
June 21, 2017: Breast: Official Journal of the European Society of Mastology
https://www.readbyqxmd.com/read/28645115/a-comprehensive-review-of-heregulins-her3-and-her4-as-potential-therapeutic-targets-in-cancer
#12
REVIEW
Jose Mauricio Mota, Katharine Ann Collier, Ricardo Lima Barros Costa, Timothy Taxter, Aparna Kalyan, Caio A Leite, Young Kwang Chae, Francis J Giles, Benedito A Carneiro
Heregulins (HRGs) bind to the receptors HER3 or HER4, induce receptor dimerization, and trigger downstream signaling that leads to tumor progression and resistance to targeted therapies. Increased expression of HRGs has been associated with worse clinical prognosis; therefore, attempts to block HRG-dependent tumor growth have been pursued. This manuscript summarizes the function and signaling of HRGs and review the preclinical evidence of its involvement in carcinogenesis, prognosis, and treatment resistance in several malignancies such as colorectal cancer, non-small cell lung cancer, ovarian cancer, and breast cancer...
June 13, 2017: Oncotarget
https://www.readbyqxmd.com/read/28644140/a-pathways-based-prediction-model-for-classifying-breast-cancer-subtypes
#13
Tong Wu, Yunfeng Wang, Ronghui Jiang, Xinliang Lu, Jiawei Tian
Breast cancer is highly heterogeneous and is classified into four subtypes characterized by specific biological traits, treatment responses, and clinical prognoses. We performed a systemic analysis of 698 breast cancer patient samples from The Cancer Genome Atlas project database. We identified 136 breast cancer genes differentially expressed among the four subtypes. Based on unsupervised clustering analysis, these 136 core genes efficiently categorized breast cancer patients into the appropriate subtypes. Functional enrichment based on Kyoto Encyclopedia of Genes and Genomes analysis identified six functional pathways regulated by these genes: JAK-STAT signaling, basal cell carcinoma, inflammatory mediator regulation of TRP channels, non-small cell lung cancer, glutamatergic synapse, and amyotrophic lateral sclerosis...
June 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/28643744/correlation-of-serum-intercellular-adhesion-molecule-1-and-vascular-endothelial-growth-factor-with-tumor-grading-and-staging-in-breast-cancer-patients
#14
Alireza Rastgoo Haghi, Amir Vahedi, Ali Akbar Shekarchi, Aziz Kamran
BACKGROUND: Breast cancer is the most common cancer among women. There are several prognostic factors for this disease. The aim of this article is to explore the correlation of serum level of vascular endothelial growth factor (VEGF) and intercellular adhesion molecule 1 (ICAM1) with tumor, node, metastasis staging and grading of breast cancer. MATERIALS AND METHODS: Serum samples of 51 patients with breast cancer were assessed with enzyme-linked immunosorbent assay for the level of VEGF and ICAM1 preoperatively...
April 2017: Journal of Cancer Research and Therapeutics
https://www.readbyqxmd.com/read/28643430/platinum-containing-regimens-for-metastatic-breast-cancer
#15
REVIEW
Sam J Egger, Melina L Willson, Jenna Morgan, Harriet S Walker, Sue Carrick, Davina Ghersi, Nicholas Wilcken
BACKGROUND: Studies have reported high tumour response rates for platinum-containing regimens in the treatment of women with metastatic breast cancer. Most of these studies were conducted prior to the 'intrinsic subtype' era, and did not specifically focus on metastatic triple-negative breast cancers (mTNBCs). OBJECTIVES: To identify and review the evidence from randomised trials comparing platinum-containing chemotherapy regimens with regimens not containing platinum in the management of women with metastatic breast cancer...
June 23, 2017: Cochrane Database of Systematic Reviews
https://www.readbyqxmd.com/read/28643022/androgen-receptor-expression-and-breast-cancer-mortality-in-a-population-based-prospective-cohort
#16
Karin Elebro, Pär-Ola Bendahl, Helena Jernström, Signe Borgquist
PURPOSE: The increase in clinical trials with androgen receptor (AR)-targeting drugs emphasizes the need of clarifying the role of AR expression in different breast cancer subtypes. AR confers good prognosis in estrogen receptor positive (ER+) breast cancer, but its role in ER-negative (ER-) breast cancer is unclear. The aim of this study was to elaborate on previous findings of a differential prognostic role for AR depending on ER status, using breast cancer mortality (BCM) as endpoint, in a population-based cohort from the Malmö Diet and Cancer Study...
June 22, 2017: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/28642035/improving-the-efficacy-of-hormone-therapy-in-breast-cancer-the-role-ofcholesterol-metabolism-in-serm-mediated-autophagy-cell-differentiation-and-death
#17
REVIEW
Julie Leignadier, Florence Dalenc, Marc Poirot, Sandrine Silvente-Poirot
Breast cancer (BC) is one of the most common female cancers in the world, with estrogen receptor (ER)-positive BC the most frequent subtype. Tamoxifen (Tam) is an effective drug that competitively binds to the ER and is routinely used for the treatment of ER-positive BC. However, a number of ER-positive BC do not respond to Tam treatment and acquired resistance is often observed, constituting a major challenge for extending patient life expectancy. The mechanisms responsible for these treatment failures remain unclear, indicating the requirement for other targets and better predictors for patient response to Tam...
June 19, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28638726/downregulation-of-antigen-presentation-associated-pathway-proteins-is-linked-to-poor-outcome-in-triple-negative-breast-cancer-patient-tumors
#18
Martin H Pedersen, Brian L Hood, Hans Christian Beck, Thomas P Conrads, Henrik J Ditzel, Rikke Leth-Larsen
Triple-negative breast cancer (TNBC) is a heterogeneous subtype with varying disease outcomes. Tumor-infiltrating lymphocytes (TILs) are frequent in TNBC and have been shown to correlate with outcome, suggesting an immunogenic component in this subtype. However, other factors intrinsic to the cancer cells may also influence outcome. To identify proteins and molecular pathways associated with recurrence in TNBC, 34 formalin-fixed paraffin-embedded (FFPE) primary TNBC tumors were investigated by global proteomic profiling using mass spectrometry...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28638122/synergistic-effects-of-various-her-inhibitors-in-combination-with-igf-1r-c-met-and-src-targeting-agents-in-breast-cancer-cell-lines
#19
Aryan Stanley, G Hossein Ashrafi, Alan M Seddon, Helmout Modjtahedi
Overexpression of HER2 has been reported in around 25% of human breast cancers. Despite recent advances in HER2 targeted therapy, many patients still experience primary and secondary resistance to such treatments, the mechanisms for which are poorly understood. Here, we investigated the sensitivity of a panel of breast cancer cell lines to treatment with various types of HER-family inhibitors alone or in combination with other tyrosine kinase inhibitors or chemotherapeutic agents. We found that treatment with the second-generation irreversible HER-family inhibitors, particularly afatinib and neratinib, were more effective than treatment with the first-generation reversible inhibitors in inhibiting growth, migration and downstream cell signalling in breast cancer cells...
June 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28634667/elevated-interleukin-13-receptor-alpha-1-expression-in-tumor-cells-is-associated-with-poor-prognosis-in-patients-with-invasive-breast-cancer
#20
Min Hui Park, Hee Jung Kwon, Jae-Ryong Kim, Byungheon Lee, Soo Jung Lee, Young Kyung Bae
BACKGROUND: Interleukin (IL)-13 is an immunoregulatory, anti-inflammatory cytokine that is produced by numerous immune cells, and plasma membrane receptor for IL-13 (IL-13R) is known to be expressed in various human malignancies and in immune cells. METHODS: The authors evaluated the expression of IL-13R alpha 1 (IL-13Rα1, an IL-13R subtype) by immunohistochemistry in tissue microarrays of 1213 invasive breast cancer (IBC) samples to determine the prognostic value of IL-13Rα1 expression...
June 20, 2017: Annals of Surgical Oncology
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