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https://www.readbyqxmd.com/read/28295245/body-mass-index-pam50-subtype-recurrence-and-survival-among-patients-with-nonmetastatic-breast-cancer
#1
Elizabeth M Cespedes Feliciano, Marilyn L Kwan, Lawrence H Kushi, Wendy Y Chen, Erin K Weltzien, Adrienne L Castillo, Carol Sweeney, Philip S Bernard, Bette J Caan
BACKGROUND: Studies of obesity and survival among patients with breast cancer produce conflicting results, possibly because of heterogeneity by molecular subtype. METHODS: This study examined whether the association of body mass index (BMI) at diagnosis with breast cancer recurrence and survival varied across subtypes defined by PAM50 (Prediction Analysis of Microarray 50) gene expression. Included were 1559 Kaiser Permanente Northern California members ages 18 to 79 years who had PAM50 assays and were diagnosed with American Joint Committee on Cancer stage I through III breast cancer from 1996 to 2013...
March 13, 2017: Cancer
https://www.readbyqxmd.com/read/28259011/clinical-use-of-biomarkers-in-breast-cancer-updated-guidelines-from-the-european-group-on-tumor-markers-egtm
#2
REVIEW
M J Duffy, N Harbeck, M Nap, R Molina, A Nicolini, E Senkus, F Cardoso
Biomarkers play an essential role in the management of patients with invasive breast cancer. For selecting patients likely to respond to endocrine therapy, both oestrogen receptors (ERs) and progesterone receptors (PRs) should be measured on all newly diagnosed invasive breast cancers. On the other hand, for selecting likely response to all forms of anti-HER2 therapy (trastuzumab, pertuzumab, lapatinib or ado-trastuzumab emtansine), determination of HER2 expression or gene copy number is mandatory. Where feasible, measurement of ER, PR and HER2 should be performed on recurrent lesions and the primary invasive tumour...
February 27, 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/28249905/intrinsic-subtypes-and-gene-expression-profiles-in-primary-and-metastatic-breast-cancer
#3
Juan Miguel Cejalvo, Eduardo Martínez de Dueñas, Patricia Galvan, Susana García-Recio, Octavio Burgués Gasión, Laia Paré, Silvia Antolin, Rossella Martinello, Isabel Blancas, Barbara Adamo, Angel Guerrero-Zotano, Montserrat Muñoz, Paolo Nuciforo, María Vidal, Ramón M Pérez, José Ignacio Chacón López-Muñiz, Rosalía Caballero, Vicente Peg, Eva Carrasco, Federico Rojo, Charles M Perou, Javier Cortes, Vincenzo Adamo, Joan Albanell, Roger R Gomis, Ana Lluch, Aleix Prat
Biological changes that occur during metastatic progression of breast cancer are still incompletely characterized. In this study, we compared intrinsic molecular subtypes and gene expression in 123 paired primary and metastatic tissues from breast cancer patients. Intrinsic subtype was identified using a PAM50 classifier and Chi-square tests determined the differences in variable distribution. The rate of subtype conversion was 0% in basal-like tumors, 23.1% in HER2-enriched (HER2-E) tumors, 30.0% in luminal B tumors and 55...
March 1, 2017: Cancer Research
https://www.readbyqxmd.com/read/28249895/individualized-breast-cancer-characterization-through-single-cell-analysis-of-tumor-and-adjacent-normal-cells
#4
Manjushree Anjanappa, Angelo A Cardoso, Lijun Cheng, Safa Mohamad, Andrea Gunawan, Susan Rice, Yan Dong, Lang Li, George E Sandusky, Edward F Srour, Harikrishna Nakshatri
There is a need to individualize assays for tumor molecular phenotyping, given variations in the differentiation status of tumor and normal tissues in different patients. To address this, we performed single-cell genomics of breast tumors and adjacent normal cells propagated for a short duration under growth conditions that enable epithelial reprogramming. Cells analyzed were either unselected for a specific subpopulation or phenotypically defined as undifferentiated and highly clonogenic ALDH+/CD49f+/EpCAM+ luminal progenitors, which express both basal cell and luminal cell-enriched genes...
March 1, 2017: Cancer Research
https://www.readbyqxmd.com/read/28238593/her2-enriched-subtype-as-a-predictor-of-pathological-complete-response-following-trastuzumab-and-lapatinib-without-chemotherapy-in-early-stage-her2-positive-breast-cancer-pamela-an-open-label-single-group-multicentre-phase-2-trial
#5
Antonio Llombart-Cussac, Javier Cortés, Laia Paré, Patricia Galván, Begoña Bermejo, Noelia Martínez, Maria Vidal, Sònia Pernas, Rafael López, Montserrat Muñoz, Paolo Nuciforo, Serafín Morales, Mafalda Oliveira, Lorena de la Peña, Alexandra Peláez, Aleix Prat
BACKGROUND: HER2-positive breast cancer consists of four intrinsic molecular subtypes-luminal A, luminal B, HER2-enriched, and basal-like-and a normal-like subtype, with the HER2-enriched subtype having the highest activation of the EGFR-HER2 pathway. We aimed to test the hypothesis that patients with the HER2-enriched subtype benefit the most from dual HER2 blockade. METHODS: PAMELA is an open-label, single-group, phase 2 trial done in 19 hospitals in Spain. We recruited female patients aged at least 18 years with previously untreated, centrally confirmed HER2-positive, stage I-IIIA invasive breast cancer regardless of hormone receptor status...
February 23, 2017: Lancet Oncology
https://www.readbyqxmd.com/read/28062443/a-novel-non-parametric-method-for-uncertainty-evaluation-of-correlation-based-molecular-signatures-its-application-on-pam50-algorithm
#6
Cristóbal Fresno, Germán Alexis González, Gabriela Alejandra Merino, Ana Georgina Flesia, Osvaldo Luis Podhajcer, Andrea Sabina Llera, Elmer Andrés Fernández
MOTIVATION: The PAM50 classifier is used to assign patients to the highest correlated breast cancer subtype irrespectively of the obtained value. Nonetheless, all subtype correlations are required to build the risk of recurrence (ROR) score, currently used in therapeutic decisions. Present subtype uncertainty estimations are not accurate, seldom considered or require a population-based approach for this context. RESULTS: Here we present a novel single-subject non-parametric uncertainty estimation based on PAM50's gene label permutations...
January 6, 2017: Bioinformatics
https://www.readbyqxmd.com/read/27926948/intrinsic-subtype-switching-and-acquired-erbb2-her2-amplifications-and-mutations-in-breast-cancer-brain-metastases
#7
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/27925203/the-genetic-landscape-of-breast-carcinomas-with-neuroendocrine-differentiation
#8
Caterina Marchiò, Felipe C Geyer, Charlotte Ky Ng, Salvatore Piscuoglio, Maria R De Filippo, Marco Cupo, Anne M Schultheis, Raymond S Lim, Kathleen A Burke, Elena Guerini-Rocco, Mauro Papotti, Larry Norton, Anna Sapino, Britta Weigelt, Jorge S Reis-Filho
Neuroendocrine breast carcinomas (NBCs) account for 2-5% of all invasive breast cancers, and are histologically similar to neuroendocrine tumours from other sites. They typically express oestrogen receptor (ER), and are HER2-negative and of luminal 'intrinsic' subtype. Here, we sought to define the mutational profile of NBCs, and to investigate whether NBCs and common forms of luminal (ER(+) /HER2(-) ) breast carcinoma show distinct repertoires of somatic mutations. Eighteen ER(+) /HER2(-) NBCs, defined as harbouring >50% of tumour cells expressing chromogranin A and/or synaptophysin, and matched normal tissues were microdissected and subjected to massively parallel sequencing targeting all exons of 254 genes most frequently mutated in breast carcinomas and/or related to DNA repair...
February 2017: Journal of Pathology
https://www.readbyqxmd.com/read/27915434/differences-in-the-mutational-landscape-of-triple-negative-breast-cancer-in-african-americans-and-caucasians
#9
Foluso O Ademuyiwa, Yu Tao, Jingqin Luo, Katherine Weilbaecher, Cynthia X Ma
BACKGROUND: Triple-negative breast cancer (TNBC) occurs at higher frequency in African Americans compared with Caucasians. It is unclear if the biology of TNBC is different in African American versus Caucasians. In this study, we sought to evaluate racial differences in the molecular pathology of TNBC. METHODS: Using data from The Cancer Genome Atlas, we identified TNBC patients with information on race. We analyzed differences in clinical characteristics, tumor somatic mutations, and gene expression patterns by race from whole exome and microarray data...
February 2017: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/27903675/a-pam50-based-chemo-endocrine-score-for-hormone-receptor-positive-breast-cancer-with-an-intermediate-risk-of-relapse
#10
Aleix Prat, Ana Lluch, Arran K Turnbull, Anita K Dunbier, Lourdes Calvo, Joan Albanell, Juan de la Haba-Rodríguez, Angels Arcusa, Ignacio Chacón, Pedro Sánchez-Rovira, Arrate Plazaola, Montse Muñoz, Laia Paré, Joel S Parker, Nuria Ribelles, Begona Jimenez, Abdul Aziz Bin Aiderus, Rosalía Caballero, Barbara Adamo, Mitch Dowsett, Eva M Carrasco, Miguel Martín, J Michael Dixon, Charles M Perou, Emilio Alba
PURPOSE: Hormone receptor-positive (HR+) breast cancer is clinically and biologically heterogeneous and subgroups with different prognostic and treatment sensitivities need to be identified. EXPERIMENTAL DESIGN: Research-based PAM50 subtyping and expression of additional genes was performed on 63 patients with HR+/HER2- disease randomized to neoadjuvant multi-agent chemotherapy versus endocrine therapy in a phase II trial. The biology associated with treatment response was used to derive a PAM50-based Chemo-Endocrine Score (CES)...
November 30, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/27899774/-a-review-multigene-assays-for-clinical-utility-in-breast-cancer
#11
REVIEW
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/27896218/hormonal-modulation-of-breast-cancer-gene-expression-implications-for-intrinsic-subtyping-in-premenopausal-women
#12
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/27861902/the-molecular-basis-of-breast-cancer-pathological-phenotypes
#13
Yujing J Heng, Susan C Lester, Gary Mk Tse, Rachel E Factor, Kimberly H Allison, Laura C Collins, Yunn-Yi Chen, Kristin C Jensen, Nicole B Johnson, Jong Cheol Jeong, Rahi Punjabi, Sandra J Shin, Kamaljeet Singh, Gregor Krings, David A Eberhard, Puay Hoon Tan, Konstanty Korski, Frederic M Waldman, David A Gutman, Melinda Sanders, Jorge S Reis-Filho, Sydney R Flanagan, Deena Ma Gendoo, Gregory M Chen, Benjamin Haibe-Kains, Giovanni Ciriello, Katherine A Hoadley, Charles M Perou, Andrew H Beck
The histopathological evaluation of morphological features in breast tumours provides prognostic information to guide therapy. Adjunct molecular analyses provide further diagnostic, prognostic and predictive information. However, there is limited knowledge of the molecular basis of morphological phenotypes in invasive breast cancer. This study integrated genomic, transcriptomic and protein data to provide a comprehensive molecular profiling of morphological features in breast cancer. Fifteen pathologists assessed 850 invasive breast cancer cases from The Cancer Genome Atlas (TCGA)...
February 2017: Journal of Pathology
https://www.readbyqxmd.com/read/27716369/patient-survival-and-tumor-characteristics-associated-with-chek2-p-i157t-findings-from-the-breast-cancer-association-consortium
#14
Taru A Muranen, Carl Blomqvist, Thilo Dörk, Anna Jakubowska, Päivi Heikkilä, Rainer Fagerholm, Dario Greco, Kristiina Aittomäki, Stig E Bojesen, Mitul Shah, Alison M Dunning, Valerie Rhenius, Per Hall, Kamila Czene, Judith S Brand, Hatef Darabi, Jenny Chang-Claude, Anja Rudolph, Børge G Nordestgaard, Fergus J Couch, Steven N Hart, Jonine Figueroa, Montserrat García-Closas, Peter A Fasching, Matthias W Beckmann, Jingmei Li, Jianjun Liu, Irene L Andrulis, Robert Winqvist, Katri Pylkäs, Arto Mannermaa, Vesa Kataja, Annika Lindblom, Sara Margolin, Jan Lubinski, Natalia Dubrowinskaja, Manjeet K Bolla, Joe Dennis, Kyriaki Michailidou, Qin Wang, Douglas F Easton, Paul D P Pharoah, Marjanka K Schmidt, Heli Nevanlinna
BACKGROUND: P.I157T is a CHEK2 missense mutation associated with a modest increase in breast cancer risk. Previously, another CHEK2 mutation, the protein truncating c.1100delC has been associated with poor prognosis of breast cancer patients. Here, we have investigated patient survival and characteristics of breast tumors of germ line p.I157T carriers. METHODS: We included in the analyses 26,801 European female breast cancer patients from 15 studies participating in the Breast Cancer Association Consortium...
October 3, 2016: Breast Cancer Research: BCR
https://www.readbyqxmd.com/read/27712195/information-theoretic-sub-network-mining-characterizes-breast-cancer-subtypes-in-terms-of-cancer-core-mechanisms
#15
Jinwoo Park, Benjamin Hur, Sungmin Rhee, Sangsoo Lim, Min-Su Kim, Kwangsoo Kim, Wonshik Han, Sun Kim
A breast cancer subtype classification scheme, PAM50, based on genetic information is widely accepted for clinical applications. On the other hands, experimental cancer biology studies have been successful in revealing the mechanisms of breast cancer and now the hallmarks of cancer have been determined to explain the core mechanisms of tumorigenesis. Thus, it is important to understand how the breast cancer subtypes are related to the cancer core mechanisms, but multiple studies are yet to address the hallmarks of breast cancer subtypes...
August 29, 2016: Journal of Bioinformatics and Computational Biology
https://www.readbyqxmd.com/read/27617288/portraying-breast-cancers-with-long-noncoding-rnas
#16
Olivier Van Grembergen, Martin Bizet, Eric J de Bony, Emilie Calonne, Pascale Putmans, Sylvain Brohée, Catharina Olsen, Mingzhou Guo, Gianluca Bontempi, Christos Sotiriou, Matthieu Defrance, François Fuks
Evidence is emerging that long noncoding RNAs (lncRNAs) may play a role in cancer development, but this role is not yet clear. We performed a genome-wide transcriptional survey to explore the lncRNA landscape across 995 breast tissue samples. We identified 215 lncRNAs whose genes are aberrantly expressed in breast tumors, as compared to normal samples. Unsupervised hierarchical clustering of breast tumors on the basis of their lncRNAs revealed four breast cancer subgroups that correlate tightly with PAM50-defined mRNA-based subtypes...
September 2016: Science Advances
https://www.readbyqxmd.com/read/27608133/a-systems-biology-approach-for-elucidating-the-interaction-of-curcumin-with-fanconi-anemia-fanc-g-protein-and-the-key-disease-targets-of-leukemia
#17
David Mahato, Dipayan Samanta, Sudit S Mukhopadhyay, R Navanietha Krishnaraj
Fanconi anemia (FA) is an autosomal recessive disorder with a high risk of malignancies including acute myeloid leukemia and squamous cell carcinoma. There is a constant search out of new potential therapeutic molecule to combat this disorder. In most cases, patients with FA develop haematological malignancies with acute myeloid leukemia and acute lymphoblastic leukemia. Identifying drugs which can efficiently block the pathways of both these disorders can be an ideal and novel strategy to treat FA. The curcumin, a natural compound obtained from turmeric is an interesting therapeutic molecule as it has been reported in the literature to combat both FA as well as leukemia...
June 2017: Journal of Receptor and Signal Transduction Research
https://www.readbyqxmd.com/read/27587435/molecular-differences-between-screen-detected-and-interval-breast-cancers-are-largely-explained-by-pam50-subtypes
#18
Jingmei Li, Emma Ivansson, Daniel Klevebring, Nicholas P Tobin, Linda S Lindström, Johanna Holm, Gabriela Prochazka, Camilla Cristando, Juni Palmgren, Sven Törnberg, Keith Humphreys, Johan Hartman, Jan Frisell, Mattias Rantalainen, Johan Lindberg, Per Hall, Jonas Bergh, Henrik Grönberg, Kamila Czene
PURPOSE: Interval breast cancer is of clinical interest as it exhibits an aggressive phenotype and evades detection by screening mammography. A comprehensive picture of somatic changes that drive tumors to become symptomatic in the screening interval can improve understanding of the biology underlying these aggressive tumors. EXPERIMENTAL DESIGN: Initiated in April 2013, Clinical Sequencing of Cancer in Sweden (Clinseq) is a scientific and clinical platform for the genomic profiling of cancer...
September 1, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/27556419/crosslink-a-novel-method-for-cross-condition-classification-of-cancer-subtypes
#19
Chifeng Ma, Konduru S Sastry, Mario Flore, Salah Gehani, Issam Al-Bozom, Yusheng Feng, Erchin Serpedin, Lotfi Chouchane, Yidong Chen, Yufei Huang
BACKGROUND: We considered the prediction of cancer classes (e.g. subtypes) using patient gene expression profiles that contain both systematic and condition-specific biases when compared with the training reference dataset. The conventional normalization-based approaches cannot guarantee that the gene signatures in the reference and prediction datasets always have the same distribution for all different conditions as the class-specific gene signatures change with the condition. Therefore, the trained classifier would work well under one condition but not under another...
August 22, 2016: BMC Genomics
https://www.readbyqxmd.com/read/27556158/comprehensive-comparison-of-molecular-portraits-between-cell-lines-and-tumors-in-breast-cancer
#20
Guanglong Jiang, Shijun Zhang, Aida Yazdanparast, Meng Li, Aniruddha Vikram Pawar, Yunlong Liu, Sai Mounika Inavolu, Lijun Cheng
BACKGROUND: Proper cell models for breast cancer primary tumors have long been the focal point in the cancer's research. The genomic comparison between cell lines and tumors can investigate the similarity and dissimilarity and help to select right cell model to mimic tumor tissues to properly evaluate the drug reaction in vitro. In this paper, a comprehensive comparison in copy number variation (CNV), mutation, mRNA expression and protein expression between 68 breast cancer cell lines and 1375 primary breast tumors is conducted and presented...
August 22, 2016: BMC Genomics
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