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Breast cancer molecular subtypes

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https://www.readbyqxmd.com/read/27926948/intrinsic-subtype-switching-and-acquired-erbb2-her2-amplifications-and-mutations-in-breast-cancer-brain-metastases
#1
Nolan Priedigkeit, Ryan J Hartmaier, Yijing Chen, Damir Vareslija, Ahmed Basudan, Rebecca J Watters, Roby Thomas, Jose P Leone, Peter C Lucas, Rohit Bhargava, Ronald L Hamilton, Juliann Chmielecki, Shannon L Puhalla, Nancy E Davidson, Steffi Oesterreich, Adam M Brufsky, Leonie Young, Adrian V Lee
Importance: Patients with breast cancer (BrCa) brain metastases (BrM) have limited therapeutic options. A better understanding of molecular alterations acquired in BrM could identify clinically actionable metastatic dependencies. Objective: To determine whether there are intrinsic subtype differences between primary tumors and matched BrM and to uncover BrM-acquired alterations that are clinically actionable. Design, Setting, and Participants: In total, 20 cases of primary breast cancer tissue and resected BrM (10 estrogen receptor [ER]-negative and 10 ER-positive) from 2 academic institutions were included...
December 7, 2016: JAMA Oncology
https://www.readbyqxmd.com/read/27926510/genetic-and-epigenetic-characterization-of-the-brca1-gene-in-brazilian-women-at-risk-for-hereditary-breast-cancer
#2
Paula Silva Felicio, Matias Eliseo Melendez, Lidia Maria Rebolho Batista Arantes, Ligia Maria Kerr, Dirce Maria Carraro, Rebeca Silveira Grasel, Natalia Campacci, Cristovam Scapulatempo-Neto, Gabriela Carvalho Fernandes, Ana Carolina de Carvalho, Edenir Inêz Palmero
This study aimed to characterize women at-risk for hereditary BC regarding their clinical and molecular characteristics (mutation and methylation in the BRCA1 gene) and correlate the gene expression levels with histopathological, clinical and family history information. BRCA1 real time qPCR was performed to evaluate methylation status and gene expression. The study included 88 women grouped according to the BRCA1 mutational status: 23 BRCA1 mutated, 22 with a Variant of Unknown Significance (VUS) in BRCA1 and 43 BRCA1 WT...
December 1, 2016: Oncotarget
https://www.readbyqxmd.com/read/27923830/a-myc-activity-signature-predicts-poor-clinical-outcomes-in-myc-associated-cancers
#3
MoonSun Jung, Amanda J Russell, Bing Liu, Joshy George, Pei Yan Liu, Tao Liu, Anna DeFazio, David D L Bowtell, Andre Oberthuer, Wendy B London, Jamie I Fletcher, Michelle Haber, Murray D Norris, Michelle J Henderson
Myc transcriptional activity is frequently deregulated in human cancers, but a Myc-driven gene signature with prognostic ability across multiple tumor types remains lacking. Here we selected 18 Myc-regulated genes from published studies of Myc family targets in epithelial ovarian cancer (EOC) and neuroblastoma. A Myc family activity score derived from the 18 genes was correlated to MYC/MYCN/MYCL1 expression in a panel of 35 cancer cell lines. The prognostic ability of this signature was evaluated in neuroblastoma, medulloblastoma, diffuse large B-cell lymphoma (DLBCL), and EOC microarray gene expression datasets using Kaplan-Meier and multivariate Cox-regression analyses, and was further validated in 42 primary neuroblastomas using qPCR...
December 6, 2016: Cancer Research
https://www.readbyqxmd.com/read/27920729/transcriptional-network-architecture-of-breast-cancer-molecular-subtypes
#4
Guillermo de Anda-Jáuregui, Tadeo E Velázquez-Caldelas, Jesús Espinal-Enríquez, Enrique Hernández-Lemus
Breast cancer heterogeneity is evident at the clinical, histological and molecular level. High throughput technologies allowed the identification of intrinsic subtypes that capture transcriptional differences among tumors. A remaining question is whether said differences are associated to a particular transcriptional program which involves different connections between the same molecules. In other words, whether particular transcriptional network architectures can be linked to specific phenotypes. In this work we infer, construct and analyze transcriptional networks from whole-genome gene expression microarrays, by using an information theory approach...
2016: Frontiers in Physiology
https://www.readbyqxmd.com/read/27915478/targeting-the-phosphatidylinositol-3-kinase-pathway-in-gastric-cancer-can-omics-improve-outcomes
#5
REVIEW
Phu Tran, Cham Nguyen, Samuel J Klempner
Phosphatidylinositol-3-kinase (PI3K) pathway signaling is an established oncogenic signal transduction pathway implicated in multiple malignancies. Therapeutic targeting of PI3K pathway components has improved outcomes in chronic lymphocytic leukemia, kidney cancer, breast cancer, and neuroendocrine tumors. Gastric cancers harbor some of the highest rates of oncogenic alterations in PI3K but attempts to translate this genomic observation have met with limited clinical success and novel approaches are needed...
November 2016: International Neurourology Journal
https://www.readbyqxmd.com/read/27913435/idh2-mutations-define-a-unique-subtype-of-breast-cancer-with-altered-nuclear-polarity
#6
Sarah Chiang, Britta Weigelt, Huei-Chi Wen, Fresia Pareja, Ashwini Raghavendra, Luciano G Martelotto, Kathleen A Burke, Thais Basili, Anqi Li, Felipe C Geyer, Salvatore Piscuoglio, Charlotte K Y Ng, Achim A Jungbluth, Jörg Balss, Stefan Pusch, Gabrielle M Baker, Kimberly S Cole, Andreas von Deimling, Julie M Batten, Jonathan D Marotti, Hwei-Choo Soh, Benjamin L McCalip, Jonathan Serrano, Raymond S Lim, Kalliopi P Siziopikou, Song Lu, Xiaolong Liu, Tarek Hammour, Edi Brogi, Matija Snuderl, A John Iafrate, Jorge S Reis-Filho, Stuart J Schnitt
Solid papillary carcinoma with reverse polarity (SPCRP) is a rare breast cancer subtype with an obscure etiology. In this study, we sought to describe its unique histopathologic features and to identify the genetic alterations that underpin SPCRP using massively parallel whole-exome and targeted sequencing. The morphologic and immunohistochemical features of SPCRP support the invasive nature of this subtype. Ten of 13 (77%) SPCRPs harbored hotspot mutations at R172 of the isocitrate dehydrogenase IDH2, of which 8 of 10 displayed concurrent pathogenic mutations affecting PIK3CA or PIK3R1 One of the IDH2 wild-type SPCRPs harbored a TET2 Q548* truncating mutation coupled with a PIK3CA H1047R hotspot mutation...
October 20, 2016: Cancer Research
https://www.readbyqxmd.com/read/27905097/novel-biomarkers-in-primary-breast-core-biopsies-to-predict-poor-response-to-neoadjuvant-chemotherapy-and-appearance-of-metastases
#7
Anna Novell, Serafin Morales, Joan Valls, Maria José Panadés, Antonieta Salud, Edelmiro Iglesias, Felip Vilardell, Xavier Matias-Guiu, Antonio Llombart-Cussac
Drug resistance has been one of the major obstacles limiting the success of cancer chemotherapy. In two thirds of breast cancer patients, large (>1cm) residual tumors are present after neoadjuvant chemotherapy (NCT). The residual tumor and involved nodes have been indicators of relapse and survival very important in breast cancer. The goal of this preliminary study was to assess the predictive significance of a panel of molecular biomarkers, related with the response to treatment or drug resistance to NCT, as determined on the diagnostic tumor...
December 1, 2016: Histology and Histopathology
https://www.readbyqxmd.com/read/27904654/augmentation-of-histone-deacetylase-3-hdac3-epigenetic-signature-at-the-interface-of-proinflammation-and-insulin-resistance-in-patients-with-type-2-diabetes
#8
Chandrakumar Sathishkumar, Paramasivam Prabu, Mahalingam Balakumar, Raji Lenin, Durai Prabhu, Ranjith Mohan Anjana, Viswanathan Mohan, Muthuswamy Balasubramanyam
BACKGROUND: A role of proinflammation has been implicated in the pathogenesis of diabetes, but the up-stream regulatory signals and molecular signatures are poorly understood. While histone modifications such as changes in histone deacetylase (HDAC) are emerging as novel epigenetic biomarkers, there is lack of studies to demonstrate their clinical relevance in diabetes. Therefore, we investigated the extent of HDAC machinery and inflammatory signals in peripheral blood mononuclear cells (PBMCs) from patients with type 2 diabetes mellitus (T2DM) compared to control subjects...
2016: Clinical Epigenetics
https://www.readbyqxmd.com/read/27902972/unravelling-site-specific-breast-cancer-metastasis-a-microrna-expression-profiling-study
#9
Willemijne A M E Schrijver, Paul J van Diest, Dutch Distant Breast Cancer Metastases Consortium, Cathy B Moelans
Distant metastasis is still the main cause of death from breast cancer. MicroRNAs (miRs) are important regulators of many physiological and pathological processes, including metastasis. Molecular breast cancer subtypes are known to show a site-specific pattern of metastases formation. In this study, we set out to determine the underlying molecular mechanisms of site-specific breast cancer metastasis by microRNA expression profiling.To identify a miR signature for metastatic breast carcinoma that could predict metastatic localization, we compared global miR expression in 23 primary breast cancer specimens with their corresponding multiple distant metastases to ovary (n=9), skin (n=12), lung (n=10), brain (n=4) and gastrointestinal tract (n=10) by miRCURY microRNA expression arrays...
November 25, 2016: Oncotarget
https://www.readbyqxmd.com/read/27901097/sequencing-based-breast-cancer-diagnostics-as-an-alternative-to-routine-biomarkers
#10
Mattias Rantalainen, Daniel Klevebring, Johan Lindberg, Emma Ivansson, Gustaf Rosin, Lorand Kis, Fuat Celebioglu, Irma Fredriksson, Kamila Czene, Jan Frisell, Johan Hartman, Jonas Bergh, Henrik Grönberg
Sequencing-based breast cancer diagnostics have the potential to replace routine biomarkers and provide molecular characterization that enable personalized precision medicine. Here we investigate the concordance between sequencing-based and routine diagnostic biomarkers and to what extent tumor sequencing contributes clinically actionable information. We applied DNA- and RNA-sequencing to characterize tumors from 307 breast cancer patients with replication in up to 739 patients. We developed models to predict status of routine biomarkers (ER, HER2,Ki-67, histological grade) from sequencing data...
November 30, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27899774/-a-review-multigene-assays-for-clinical-utility-in-breast-cancer
#11
Kazuhiro Araki, Yoshinori Ito
Multigene assays that simultaneously measure the expression of various breast cancer genes have been developed to guide the use of adjuvant chemotherapy in early breast cancer. The efficacy of adjuvant therapies depends on the recurrence risk for an individual patient. As a result, accurate prediction of the recurrence risk is vital for precise adjuvant chemotherapy in individual breast cancer patients. The recurrence risk as typically assessed by conventional examination of histological data of immuno-histological biomarkers(ER, PR, HER2, and Ki-67)is not sufficient to select subsets of patients...
November 2016: Gan to Kagaku Ryoho. Cancer & Chemotherapy
https://www.readbyqxmd.com/read/27896993/frequent-subgraph-mining-of-personalized-signaling-pathway-networks-groups-patients-with-frequently-dysregulated-disease-pathways-and-predicts-prognosis
#12
Arda Durmaz, Tim A D Henderson, Douglas Brubaker, Gurkan Bebek
MOTIVATION: Large scale genomics studies have generated comprehensive molecular characterization of numerous cancer types. Subtypes for many tumor types have been established; however, these classifications are based on molecular characteristics of a small gene sets with limited power to detect dysregulation at the patient level. We hypothesize that frequent graph mining of pathways to gather pathways functionally relevant to tumors can characterize tumor types and provide opportunities for personalized therapies...
2016: Pacific Symposium on Biocomputing
https://www.readbyqxmd.com/read/27896700/fat4-functions-as-a-tumor-suppressor-in-triple-negative-breast-cancer
#13
Lingmi Hou, Maoshan Chen, Xiaobo Zhao, Jingdong Li, Shishan Deng, Jiani Hu, Hongwei Yang, Jun Jiang
Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer that is often associated with biologic behavior with frequent distant metastasis. FAT tumor suppressor homolog 4 (FAT4), a cadherin-related protein, is involved in a variety of biological processes as a tumor suppressor; however, the role of FAT4 in TNBC is still unclear. The aim of our study was to identify the role of FAT4 in TNBC and examine the underlying molecular mechanisms. The expression of FAT4 was evaluated by immunohistochemistry, western blotting, and qRT-PCR in a series of TNBC tissues...
November 28, 2016: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/27896218/hormonal-modulation-of-breast-cancer-gene-expression-implications-for-intrinsic-subtyping-in-premenopausal-women
#14
REVIEW
Sarah M Bernhardt, Pallave Dasari, David Walsh, Amanda R Townsend, Timothy J Price, Wendy V Ingman
Clinics are increasingly adopting gene-expression profiling to diagnose breast cancer subtype, providing an intrinsic, molecular portrait of the tumor. For example, the PAM50-based Prosigna test quantifies expression of 50 key genes to classify breast cancer subtype, and this method of classification has been demonstrated to be superior over traditional immunohistochemical methods that detect proteins, to predict risk of disease recurrence. However, these tests were largely developed and validated using breast cancer samples from postmenopausal women...
2016: Frontiers in Oncology
https://www.readbyqxmd.com/read/27895868/immunohistochemical-subtypes-of-breast-cancer-correlation-with-clinicopathological-and-radiological-factors
#15
Yu-Mee Sohn, Kyunghwa Han, Mirinae Seo
BACKGROUND: The relationship between biomarkers and imaging features is important because imaging findings can predict molecular features. OBJECTIVES: To investigate the relationship between clinicopathologic and radiologic factors and the immunohistochemical (IHC) profiles associated with breast cancer. PATIENTS AND METHODS: From December 2004 to September 2013, 200 patients (mean age, 56 years; range, 29 - 82 years) were diagnosed with breast cancer and underwent surgery at our institution...
October 2016: Iranian Journal of Radiology: a Quarterly Journal Published By the Iranian Radiological Society
https://www.readbyqxmd.com/read/27895496/identification-of-lncrna-fam83h-as1-as-a-novel-prognostic-marker-in-luminal-subtype-breast-cancer
#16
Fan Yang, Shi-Xu Lv, Lin Lv, Ye-Huan Liu, Si-Yang Dong, Zhi-Han Yao, Xuan-Xuan Dai, Xiao-Hua Zhang, Ou-Chen Wang
BACKGROUND: Luminal subtype breast cancer accounts for a predominant number of breast cancers. Considering the heterogeneity of the disease, it is urgent to develop novel biomarkers to improve risk stratification and optimize therapy choices. Long non-coding RNA (lncRNA) represents an emerging and understudied class of transcripts that play a significant role in cancer biology. Growing knowledge of cancer-associated lncRNAs contributes to the development of molecular markers for prognosis evaluation and gene therapy...
2016: OncoTargets and Therapy
https://www.readbyqxmd.com/read/27893626/molecular-profiling-using-breast-cancer-subtype-to-plan-for-breast-reconstruction
#17
Lars Johan Sandberg, Mark W Clemens, W F Symmans, Vicente Valero, Abigail S Caudle, Benjamin Smith, Henry M Kuerer, Limin Hsu, Steven J Kronowitz
BACKGROUND: Molecular profiling using breast cancer subtype has an increasing role in the multidisciplinary care of the breast cancer patient. We sought to determine the role of breast cancer subtyping in breast reconstruction and specifically if breast cancer subtyping can determine the need for postmastectomy radiation therapy (PMRT) and predict recurrence-free survival (RFS) to plan for the timing and technique of breast reconstruction. METHODS: We reviewed prospectively collected data from 1931 reconstructed breasts in breast cancer patients who underwent mastectomy between November 1999 and December 2012...
November 21, 2016: Plastic and Reconstructive Surgery
https://www.readbyqxmd.com/read/27891540/advancement-of-mass-spectrometry-based-proteomics-technologies-to-explore-triple-negative-breast-cancer
#18
REVIEW
Sayem Miah, Charles A S Banks, Mark K Adams, Laurence Florens, Kiven E Lukong, Michael P Washburn
Understanding the complexity of cancer biology requires extensive information about the cancer proteome over the course of the disease. The recent advances in mass spectrometry-based proteomics technologies have led to the accumulation of an incredible amount of such proteomic information. This information allows us to identify protein signatures or protein biomarkers, which can be used to improve cancer diagnosis, prognosis and treatment. For example, mass spectrometry-based proteomics has been used in breast cancer research for over two decades to elucidate protein function...
November 28, 2016: Molecular BioSystems
https://www.readbyqxmd.com/read/27889196/impact-of-molecular-subtypes-classification-concordance-between-preoperative-core-needle-biopsy-and-surgical-specimen-on-early-breast-cancer-management-single-institution-experience-and-review-of-published-literature
#19
I Meattini, G Bicchierai, C Saieva, D De Benedetto, I Desideri, C Becherini, D Abdulcadir, E Vanzi, C Boeri, S Gabbrielli, F Lucci, L Sanchez, D Casella, M Bernini, L Orzalesi, V Vezzosi, D Greto, M Mangoni, S Bianchi, L Livi, J Nori
BACKGROUND: Core needle biopsy (CNB) plays a crucial role as diagnostic tool for breast cancer (BC). The characterization of biomarkers status before surgical treatment is crucial when primary systemic therapy is a therapeutic option. The aim of this analysis was to report concordance between preoperative CNB and surgical specimen (SS) in evaluating biomarkers and molecular subtypes. METHODS: Data have been collected from a cohort of 101 patients affected by early BC treated at Careggi Florence University Hospital, between January 2014 and March 2015...
November 17, 2016: European Journal of Surgical Oncology
https://www.readbyqxmd.com/read/27888707/up-regulation-of-rfc3-promotes-triple-negative-breast-cancer-metastasis-and-is-associated-with-poor-prognosis-via-emt
#20
Zhen-Yu He, San-Gang Wu, Fang Peng, Qun Zhang, Ying Luo, Ming Chen, Yong Bao
Triple-negative breast cancer (TNBC) was regarded as the most aggressive and mortal subtype of breast cancer (BC) since the molecular subtype system has been established. Abundant studies have revealed that epithelial-mesenchymal transition (EMT) played a pivotal role during breast cancer metastasis and progression, especially in TNBC. Herein, we showed that inhibition the expression of replication factor C subunit 3 (RFC3) significantly attenuated TNBC metastasis and progression, which was associated with EMT signal pathway...
November 23, 2016: Translational Oncology
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