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Breast cancer genomic testing

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https://www.readbyqxmd.com/read/28440475/a-nine-mirna-signature-as-a-potential-diagnostic-marker-for-breast-carcinoma-an-integrated-study-of-1-110-cases
#1
Dan-Dan Xiong, Jun Lv, Kang-Lai Wei, Zhen-Bo Feng, Ji-Tian Chen, Ke-Cheng Liu, Gang Chen, Dian-Zhong Luo
Growing evidence indicates that microRNAs (miRNAs) play critical roles in the initiation and progression of breast carcinoma (BC) and are promising diagnostic biomarkers. In the present study, we aimed to identify a multi-marker miRNA pool with high diagnostic performance for BC. We collected miRNA expression profiles of BC samples and normal breast tissues from The Cancer Genome Atlas (TCGA) and screened differentially expressed miRNAs by conducting two‑sample t-tests and by calculating log2 fold-change (log2FC) ratios...
April 25, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28428927/limitations-of-personalized-medicine-and-gene-assays-for-breast-cancer
#2
David Tiberi, Laura Masucci, Daniel Shedid, Isabelle Roy, Toni Vu, Erica Patocskai, André Robidoux, Philip Wong
Adjuvant systemic treatments reduce the risk of breast cancer recurrence following the local treatment of primary stage I-III breast cancers. For patients with hormone-positive breast cancers receiving hormonal therapy, the risk of distant recurrence is under 20% and therefore, many patients may potentially be spared of chemotherapy. Consequently, several molecular signatures based on gene expression were developed to better determine which breast cancer patients would benefit from chemotherapy. We present the case of a 62-year-old woman diagnosed with an early stage hormone receptor-positive breast cancer that was treated with a partial mastectomy...
March 17, 2017: Curēus
https://www.readbyqxmd.com/read/28428277/immune-gene-expression-is-associated-with-genomic-aberrations-in-breast-cancer
#3
Anton Safonov, Tingting Jiang, Giampaolo Bianchini, Balázs Győrffy, Thomas Karn, Christos Hatzis, Lajos Pusztai
The presence of tumor-infiltrating lymphocytes (TIL) is a favorable prognostic factor in breast cancer, but what drives immune infiltration remains unknown. Here we examine if clonal heterogeneity, total mutation load, neoantigen load, copy number variations (CNV), gene- or pathway-level somatic mutations, or germline polymorphisms (SNP) are associated with immune metagene expression in breast cancer subtypes. Thirteen published immune metagenes correlated separately with genomic metrics in the 3 major breast cancer subtypes...
April 20, 2017: Cancer Research
https://www.readbyqxmd.com/read/28423538/gene-regulatory-pattern-analysis-reveals-essential-role-of-core-transcriptional-factors-activation-in-triple-negative-breast-cancer
#4
Li Min, Cheng Zhang, Like Qu, Jialiang Huang, Lan Jiang, Jiafei Liu, Luca Pinello, Guo-Cheng Yuan, Chengchao Shou
BACKGROUND: Triple-negative breast cancer (TNBC) is an aggressive breast cancer subtype. Genome-scale molecular characteristics and regulatory mechanisms that distinguish TNBC from other subtypes remain incompletely characterized. RESULTS: By combining gene expression analysis and PANDA network, we defined three different TF regulatory patterns. A core TNBC-Specific TF Activation Driven Pattern (TNBCac) was specifically identified in TNBC by computational analysis...
March 28, 2017: Oncotarget
https://www.readbyqxmd.com/read/28422318/computational-analysis-of-breast-cancer-gwas-loci-identifies-the-putative-deleterious-effect-of-stxbp4-and-znf404-gene-variants
#5
Tariq Ahmad Masoodi, Babajan Banaganapalli, Venkatesh Vaidyanathan, Venkateswar Rao Talluri, Noor Ahmad Shaik
The genome-wide association studies (GWAS) have enabled us in identifying different breast cancer susceptibility loci. However, majority of these are non-coding variants with no annotated biological function. We investigated such 78 noncoding genome wide associated SNPs of breast cancer and further expanded the list to 2162 variants with strong linkage-disequilibrium (LD, r2 ≥0.8). Using multiple publically available algorithms such as CADD, GWAVA and FATHAMM, we classified all these variants in to deleterious, damaging or benign categories...
April 19, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28417335/poor-prognosis-of-patients-with-triple-negative-breast-cancer-can-be-stratified-by-rank-and-rankl-dual-expression
#6
Monica E Reyes, Takeo Fujii, Daniel Branstetter, Savitri Krishnamurthy, Hiroko Masuda, Xiaoping Wang, James M Reuben, Wendy A Woodward, Beatrice J Edwards, Gabriel N Hortobagyi, Debu Tripathy, William C Dougall, Bedrich L Eckhardt, Naoto T Ueno
PURPOSE: As clinical studies have correlated RANK expression levels with survival in breast cancer, and that RANK signaling is dependent on its cognate ligand RANKL, we hypothesized that dual protein expression further stratifies the poor outcome in TNBC. METHODS: RANK mRNA and protein expression was evaluated in TNBC using genomic databases, cell lines and in a tissue microarray of curated primary tumor samples derived from 87 patients with TNBC. RANK expression was evaluated either by Mann-Whitney U test on log-normalized gene expression data or by Student's t test on FACS data...
April 17, 2017: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/28412725/immunohistochemical-ki67-after-short-term-hormone-therapy-identifies-low-risk-breast-cancers-as-reliably-as-genomic-markers
#7
Takayuki Iwamoto, Toyomasa Katagiri, Naoki Niikura, Yuichiro Miyoshi, Mariko Kochi, Tomohiro Nogami, Tadahiko Shien, Takayuki Motoki, Naruto Taira, Masako Omori, Yutaka Tokuda, Toshiyoshi Fujiwara, Hiroyoshi Doihara, Balazs Gyorffy, Junji Matsuoka
BACKGROUND: The purpose of this study was to test whether immunohistochemical (IHC) Ki67 levels after short-term preoperative hormone therapy (post-Ki67) predict similar numbers of patients with favorable prognoses as genomic markers. RESULTS: Thirty paired cases (60 samples) were enrolled in this study. Post-Ki67 levels were significantly lower than pre-treatment Ki67 levels (P < 0.001). Post-Ki67 predicted more low-risk cases (83.3%, 25/30) than pre-genomic surrogate signature(GSS) (66...
February 16, 2017: Oncotarget
https://www.readbyqxmd.com/read/28401970/integrating-multiple-omics-data-for-the-discovery-of-potential-beclin-1-interactions-in-breast-cancer
#8
Yi Chen, Xuan Wang, Guan Wang, Zhaozhi Li, Jinjin Wang, Lingyu Huang, Ziyi Qin, Xiang Yuan, Zhong Cheng, Shu Zhang, Yiqiong Yin, Jun He
Breast cancer has been reported as one of the most frequently diagnosed malignant diseases and the leading cause of cancer death in women all around the world. Furthermore, this complicated cancer is divided into multiple subtypes which present different clinical symptoms and need correspondingly directed therapy. We took BECN1, a core gene in autophagy performing a tumor inhibitory effect, as a starting point. The study in this paper aims to identify genes related to breast cancer and its multiple subtypes by integrating multiple omics data using the least absolute shrinkage and selection operator (LASSO), which is a statistical method that can integrate more than two types of omics data...
April 12, 2017: Molecular BioSystems
https://www.readbyqxmd.com/read/28401821/-70-gene-signature-as-an-aid-to-treatment-decisions-in-early-stage-breast-cancer
#9
J J M van der Hoeven
OBJECTIVE: The 70-gene signature test (MammaPrint) has been shown to improve prediction of clinical outcome in women with early-stage breast cancer. We sought to provide prospective evidence of the clinical utility of the addition of the 70-gene signature to standard clinical-pathological criteria in selecting patients for adjuvant chemotherapy. METHODS: In this randomized, phase 3 study, we enrolled 6693 women with early-stage breast cancer and determined their genomic risk (using the 70-gene signature) and their clinical risk (using a modified version of Adjuvant! Online)...
2017: Nederlands Tijdschrift Voor Geneeskunde
https://www.readbyqxmd.com/read/28401819/-a-plea-for-selective-use-of-the-mammaprint-test
#10
M de Boer, A C Voogd, V C G Tjan-Heijnen
Recently, the results of the MINDACT study were published in The New England Journal of Medicine. The authors conclude that the MammaPrint test can prevent the use of chemotherapy in about 50% of breast cancer patients with a high-risk clinical profile because of the presence of a genomic low risk MammaPrint. We believe that the decision to use chemotherapy should not be based solely on the outcome of the MammaPrint test, as is suggested by the authors, but also on clinical factors, such as tumour size, nodal status and grade...
2017: Nederlands Tijdschrift Voor Geneeskunde
https://www.readbyqxmd.com/read/28399564/interactions-between-genome-wide-significant-genetic-variants-and-circulating-concentrations-of-25-hydroxyvitamin-d-in-relation-to-prostate-cancer-risk-in-the-national-cancer-institute-bpc3
#11
Vasiliki I Dimitrakopoulou, Ruth C Travis, Irene M Shui, Alison Mondul, Demetrius Albanes, Jarmo Virtamo, Antonio Agudo, Heiner Boeing, H Bas Bueno-de-Mesquita, Marc J Gunter, Mattias Johansson, Kay-Tee Khaw, Kim Overvad, Domenico Palli, Antonia Trichopoulou, Edward Giovannucci, David J Hunter, Sara Lindström, Walter Willett, J Michael Gaziano, Meir Stampfer, Christine Berg, Sonja I Berndt, Amanda Black, Robert N Hoover, Peter Kraft, Timothy J Key, Konstantinos K Tsilidis
Genome-wide association studies (GWAS) have identified over 100 single nucleotide polymorphisms (SNPs) associated with prostate cancer. However, information on the mechanistic basis for some associations is limited. Recent research has been directed towards the potential association of vitamin D concentrations and prostate cancer, but little is known about whether the aforementioned genetic associations are modified by vitamin D. We investigated the associations of 46 GWAS-identified SNPs, circulating concentrations of 25-hydroxyvitamin D (25(OH)D), and prostate cancer (3,811 cases, 511 of whom died from the disease, compared with 2,980 controls-from 5 cohort studies that recruited participants over several periods beginning in the 1980s)...
March 15, 2017: American Journal of Epidemiology
https://www.readbyqxmd.com/read/28398847/traceback-a-proposed-framework-to-increase-identification-and-genetic-counseling-of-brca1-and-brca2-mutation-carriers-through-family-based-outreach
#12
Goli Samimi, Marcus Q Bernardini, Lawrence C Brody, Charlisse F Caga-Anan, Ian G Campbell, Georgia Chenevix-Trench, Fergus J Couch, Michael Dean, Joanne A de Hullu, Susan M Domchek, Ronny Drapkin, Heather Spencer Feigelson, Michael Friedlander, Mia M Gaudet, Marline G Harmsen, Karen Hurley, Paul A James, Janice S Kwon, Felicitas Lacbawan, Stephanie Lheureux, Phuong L Mai, Leah E Mechanic, Lori M Minasian, Evan R Myers, Mark E Robson, Susan J Ramus, Lisa F Rezende, Patricia A Shaw, Thomas P Slavin, Elizabeth M Swisher, Masataka Takenaka, David D Bowtell, Mark E Sherman
In May 2016, the Division of Cancer Prevention and the Division of Cancer Control and Population Sciences, National Cancer Institute, convened a workshop to discuss a conceptual framework for identifying and genetically testing previously diagnosed but unreferred patients with ovarian cancer and other unrecognized BRCA1 or BRCA2 mutation carriers to improve the detection of families at risk for breast or ovarian cancer. The concept, designated Traceback, was prompted by the recognition that although BRCA1 and BRCA2 mutations are frequent in women with ovarian cancer, many such women have not been tested, especially if their diagnosis predated changes in testing guidelines...
April 11, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28391240/physical-confirmation-and-comparative-genomics-of-the-rat-mammary-carcinoma-susceptibility-3-quantitative-trait-locus
#13
Saasha Le, Zachary C Martin, David J Samuelson
Human breast and rat mammary cancer susceptibility are complex phenotypes where complete sets of risk associated loci remain to be identified for both species. We tested multiple congenic rat strains to physically confirm and positionally map rat Mammary carcinoma susceptibility 3 (Mcs3), a mammary cancer resistance allele previously predicted at Rattus norvegicus chromosome 1 (RNO1). The mammary cancer susceptible Wistar Furth (WF) strain was the recipient, and the mammary cancer resistant Copenhagen (Cop) strain was the RNO1-segment donor for congenics...
April 8, 2017: G3: Genes—Genomes—Genetics
https://www.readbyqxmd.com/read/28388918/tea-camellia-sinensis-infusions-ameliorate-cancer-in-4ti-metastatic-breast-cancer-model
#14
Karori S Mbuthia, Paul O Mireji, Raphael M Ngure, Francesca Stomeo, Martina Kyallo, Chalo Muoki, Francis N Wachira
BACKGROUND: Tea (Camellia sinensis) infusions are widely consumed beverages with numerous health benefits. However, physiological and molecular responses mediating these activities are poorly understood. METHOD: Three replicates of 4TI cancer cell suspension (2.0 × 10(5) cells/ml) were challenged in vitro with various concentrations of green, black and purple tea infusions to asseses their cytoxicity and associated differentially expressed genes in the cells...
April 7, 2017: BMC Complementary and Alternative Medicine
https://www.readbyqxmd.com/read/28388533/brca1-haploinsufficiency-cell-autonomously-activates-rankl-expression-and-generates-denosumab-responsive-breast-cancer-initiating-cells
#15
Elisabet Cuyàs, Bruna Corominas-Faja, María Muñoz-San Martín, Begoña Martin-Castillo, Ruth Lupu, Joan Brunet, Joaquim Bosch-Barrera, Javier A Menendez
Denosumab, a monoclonal antibody to the receptor activator of nuclear factor-κB ligand (RANKL), might be a novel preventative therapy for BRCA1-mutation carriers at high risk of developing breast cancer. Beyond its well-recognized bone-targeted activity impeding osteoclastogenesis, denosumab has been proposed to interfere with the cross-talk between RANKL-producing sensor cells and cancer-initiating RANK+ responder cells that reside within premalignant tissues of BRCA1-mutation carriers. We herein tested the alternative but not mutually exclusive hypothesis that BRCA1 deficiency might cell-autonomously activate RANKL expression to generate cellular states with cancer stem cell (CSC)-like properties...
March 25, 2017: Oncotarget
https://www.readbyqxmd.com/read/28379620/genome-wide-copy-number-variation-pattern-analysis-and-a-classification-signature-for-non-small-cell-lung-cancer
#16
Jia-Hao Bi, Zhe-Wei Qiu, Adi F Gazdar, Kai Song
The accurate classification of non-small cell lung carcinoma (NSCLC) into lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) is essential for both clinical practice and lung cancer research. Although the standard WHO diagnosis of NSCLC on biopsy material is rapid and economic, more than 13% of NSCLC tumors in the USA are not further classified. The purpose of this study was to analyze the genome-wide pattern differences in copy number variations (CNVs) and to develop a CNV signature as an adjunct test for the routine histopathologic classification of NSCLCs...
April 5, 2017: Genes, Chromosomes & Cancer
https://www.readbyqxmd.com/read/28377418/characterizing-genetic-susceptibility-to-breast-cancer-in-women-of-african-ancestry
#17
Ye Feng, Suhn K Rhie, Dezheng Huo, Edward A Ruiz-Narvaez, Stephen A Haddad, Christine B Ambrosone, Esther M John, Leslie Bernstein, Wei Zheng, Jennifer J Hu, Regina G Ziegler, Sarah Nyante, Elisa V Bandera, Sue Ann Ingles, Michael F Press, Sandra L Deming, Jorge L Rodriguez-Gil, Yonglan Zheng, Song Yao, Yoo Jeong Han, Temidayo O Ogundiran, Timothy R Rebbeck, Clement Adebamowo, Oladosu Ojengbede, Adeyinka G Falusi, Anselm Hennis, Barbara Nemesure, Stefan Ambs, William Blot, Qiuyin Cai, Lisa Signorello, Katherine L Nathanson, Kathryn L Lunetta, Lara E Sucheston-Campbell, Jeannette T Bensen, Stephen J Chanock, Loic Le Marchand, Andrew F Olshan, Laurence N Kolonel, David V Conti, Gerhard Coetzee, Daniel O Stram, Olufunmilayo I Olopade, Julie R Palmer, Christopher A Haiman
BACKGROUND: Genome-wide association studies have identified ~100 common genetic variants associated with breast cancer risk, the majority of which were discovered in women of European ancestry. Due to different patterns of linkage disequilibrium, many of these genetic markers may not represent signals in populations of African ancestry. METHODS: We tested 74 breast cancer risk variants and conducted fine-mapping of these susceptibility regions in 6,522 breast cancer cases and 7,643 controls of African ancestry from three genetic consortia (AABC, AMBER and ROOT)...
April 4, 2017: Cancer Epidemiology, Biomarkers & Prevention
https://www.readbyqxmd.com/read/28376177/progesterone-receptor-isoform-ratio-a-breast-cancer-prognostic-and-predictive-factor-for-antiprogestin-responsiveness
#18
Paola A Rojas, María May, Gonzalo R Sequeira, Andrés Elia, Michelle Alvarez, Paula Martínez, Pedro Gonzalez, Stephen Hewitt, Xiaping He, Charles M Perou, Alfredo Molinolo, Luz Gibbons, Martin C Abba, Hugo Gass, Claudia Lanari
Background: Compelling evidence shows that progestins regulate breast cancer growth. Using preclinical models, we demonstrated that antiprogestins are inhibitory when the level of progesterone receptor isoform A (PR-A) is higher than that of isoform B (PR-B) and that they might stimulate growth when PR-B is predominant. The aims of this study were to investigate ex vivo responses to mifepristone (MFP) in breast carcinomas with different PR isoform ratios and to examine their clinical and molecular characteristics...
July 1, 2017: Journal of the National Cancer Institute
https://www.readbyqxmd.com/read/28376176/tumor-sequencing-and-patient-derived-xenografts-in-the-neoadjuvant-treatment-of-breast-cancer
#19
Matthew P Goetz, Krishna R Kalari, Vera J Suman, Ann M Moyer, Jia Yu, Daniel W Visscher, Travis J Dockter, Peter T Vedell, Jason P Sinnwell, Xiaojia Tang, Kevin J Thompson, Sarah A McLaughlin, Alvaro Moreno-Aspitia, John A Copland, Donald W Northfelt, Richard J Gray, Katie Hunt, Amy Conners, Richard Weinshilboum, Liewei Wang, Judy C Boughey
Background: Breast cancer patients with residual disease after neoadjuvant chemotherapy (NAC) have increased recurrence risk. Molecular characterization, knowledge of NAC response, and simultaneous generation of patient-derived xenografts (PDXs) may accelerate drug development. However, the feasibility of this approach is unknown. Methods: We conducted a prospective study of 140 breast cancer patients treated with NAC and performed tumor and germline sequencing and generated patient-derived xenografts (PDXs) using core needle biopsies...
July 1, 2017: Journal of the National Cancer Institute
https://www.readbyqxmd.com/read/28374160/a-case-of-contralateral-breast-cancer-and-skin-cancer-associated-with-nbn-heterozygous-pathogenic-variant-c-698_701delaaca
#20
Jennifer Gass, Jessica Jackson, Sarah Macklin, Patrick Blackburn, Stephanie Hines, Paldeep S Atwal
Approximately 39.6% of people will be diagnosed with cancer during their lifetime. Several factors including, lifestyle, environment and genetics may play a role in its development. Understanding these causes will greatly improve treatment methods, prevention, and survival rates of these patients. Our patient, who has a positive family history of cancer, presented with contralateral breast cancer and multiple skin malignancies. Genetic testing revealed a frameshift variant in NBN. This gene encodes the protein, nibrin, which is involved in maintaining genomic stability...
April 3, 2017: Familial Cancer
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