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https://www.readbyqxmd.com/read/29137653/prognostic-value-of-pam50-and-risk-of-recurrence-score-in-patients-with-early-stage-breast-cancer-with-long-term-follow-up
#1
Hege O Ohnstad, Elin Borgen, Ragnhild S Falk, Tonje G Lien, Marit Aaserud, My Anh T Sveli, Jon A Kyte, Vessela N Kristensen, Gry A Geitvik, Ellen Schlichting, Erik A Wist, Therese Sørlie, Hege G Russnes, Bjørn Naume
BACKGROUND: The aim of this study was to investigate the prognostic value of the PAM50 intrinsic subtypes and risk of recurrence (ROR) score in patients with early breast cancer and long-term follow-up. A special focus was placed on hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) pN0 patients not treated with chemotherapy. METHODS: Patients with early breast cancer (n = 653) enrolled in the observational Oslo1 study (1995-1998) were followed for distant recurrence and breast cancer death...
November 14, 2017: Breast Cancer Research: BCR
https://www.readbyqxmd.com/read/29137596/analysis-of-breast-cancer-subtypes-by-ap-isa-biclustering
#2
Liying Yang, Yunyan Shen, Xiguo Yuan, Junying Zhang, Jianhua Wei
BACKGROUND: Gene expression profiling has led to the definition of breast cancer molecular subtypes: Basal-like, HER2-enriched, LuminalA, LuminalB and Normal-like. Different subtypes exhibit diverse responses to treatment. In the past years, several traditional clustering algorithms have been applied to analyze gene expression profiling. However, accurate identification of breast cancer subtypes, especially within highly variable LuminalA subtype, remains a challenge. Furthermore, the relationship between DNA methylation and expression level in different breast cancer subtypes is not clear...
November 14, 2017: BMC Bioinformatics
https://www.readbyqxmd.com/read/29099283/lowly-methylated-region-analysis-identifies-ebf1-as-a-potential-epigenetic-modifier-in-breast-cancer
#3
Nora Fernandez-Jimenez, Athena Sklias, Szilvia Ecsedi, Vincent Cahais, Davide Degli-Esposti, Antonin Jay, Pierre Benoit Ancey, Hae Dong Woo, Hector Hernandez-Vargas, Zdenko Herceg
Breast cancer (BC) encompasses heterogeneous pathologies with different subtypes exhibiting distinct molecular changes, including those related to DNA methylation. However, the role of these changes in mediating BC heterogeneity is poorly understood. Lowly methylated regions (LMRs), non-CpG island loci that usually contain transcription factor (TF) binding sites, have been suggested to act as regulatory elements that define cellular identity. In this study, we aimed to identify the key subtype-specific TFs that may lead to LMR generation and shape the BC methylome and transcription program...
November 3, 2017: Epigenetics: Official Journal of the DNA Methylation Society
https://www.readbyqxmd.com/read/29061527/pam50-unbiased-multimodal-template-of-the-brainstem-and-spinal-cord-aligned-with-the-icbm152-space
#4
Benjamin De Leener, Vladimir S Fonov, D Louis Collins, Virginie Callot, Nikola Stikov, Julien Cohen-Adad
Template-based analysis of multi-parametric MRI data of the spinal cord sets the foundation for standardization and reproducibility, thereby helping the discovery of new biomarkers of spinal-related diseases. While MRI templates of the spinal cord have been recently introduced, none of them cover the entire spinal cord. In this study, we introduced an unbiased multimodal MRI template of the spinal cord and the brainstem, called PAM50, which is anatomically compatible with the ICBM152 brain template and uses the same coordinate system...
October 21, 2017: NeuroImage
https://www.readbyqxmd.com/read/29050296/reverse-phase-protein-array-identification-of-triple-negative-breast-cancer-subtypes-and-comparison-with-mrna-molecular-subtypes
#5
Hiroko Masuda, Yuan Qi, Shuying Liu, Naoki Hayashi, Takahiro Kogawa, Gabriel N Hortobagyi, Debu Tripathy, Naoto T Ueno
BACKGROUND: Reverse phase protein array (RPPA) analysis, allows investigation of potential targets at the functional protein level,. We identified TNBC subtypes at the protein level using RPPA and compared them with mRNA molecular subtypes (TNBCtype, TNBCtype-4, and PAM50) that is unique in its availability of both RPPA and mRNA analyses. METHODS: We classified the samples from 80 TNBC patients using both k-means and hierarchical consensus clustering analysis and performed Ingenuity Pathway Analysis...
September 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/28985022/endocrine-sensitivity-of-estrogen-receptor-positive-breast-cancer-is-negatively-correlated-with-aspartate-%C3%AE-hydroxylase-expression
#6
Masafumi Shimoda, Ami Hori, Jack R Wands, Ryo Tsunashima, Yasuto Naoi, Tomohiro Miyake, Tomonori Tanei, Naofumi Kagara, Kenzo Shimazu, Seung Jin Kim, Shinzaburo Noguchi
Although prognostic markers for early estrogen receptor (ER)-positive breast cancer have been extensively developed, predictive markers for adjuvant endocrine therapy are still lacking. Focusing on the mechanisms underlying endocrine resistance, we investigated whether the endocrine sensitivity of ER-positive breast cancer cells was correlated with the expression of aspartate-β-hydroxylase (ASPH), which is involved in the development of hepatocellular carcinoma. ASPH expression in ER-positive and tamoxifen-resistant breast cancer cells was upregulated by the MAPK and phosphoinositide-3 kinase (PI3K) pathways, which both play pivotal roles in endocrine resistance...
October 6, 2017: Cancer Science
https://www.readbyqxmd.com/read/28984296/male-breast-cancer-correlation-between-immunohistochemical-subtyping-and-pam50-intrinsic-subtypes-and-the-subsequent-clinical-outcomes
#7
Alfonso Sánchez-Muñoz, Luis Vicioso, Angela Santonja, Martina Álvarez, Yéssica Plata-Fernández, José Miramón, Irene Zarcos, César L Ramírez-Tortosa, Julio Montes-Torres, José M Jerez, Vanessa de Luque, Casilda Llácer, Cristina E Fernández-De Sousa, Lidia Pérez-Villa, Emilio Alba
Male breast cancer is a rare disease that is still poorly understood. It is mainly classified by immunohistochemistry as a luminal disease. In this study, we assess for the first time the correlation between molecular subtypes based on a validated six-marker immunohistochemical panel and PAM50 signature in male breast cancer, and the subsequent clinical outcome of these different subtypes. We collected 67 surgical specimens of invasive male breast cancer from four different Spanish pathology laboratories. Immunohistochemical staining for the six-marker panel was performed on tissue microarrays...
October 6, 2017: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/28972043/gene-expression-signatures-and-immunohistochemical-subtypes-add-prognostic-value-to-each-other-in-breast-cancer-cohorts
#8
Arian Lundberg, Linda Sofie Lindström, J Chuck Harrell, Claudette Falato, Joseph W Carlson, Paul K Wright, Theodoros Foukakis, Charles M Perou, Kamila Czene, Jonas Bergh, Nicholas P Tobin
PURPOSE: Gene signatures and Ki67 stratify the same breast tumour into opposing good/poor prognosis groups in approximately 20% of patients. Given this discrepancy, we hypothesized that the combination of a clinically relevant signature and immunohistochemical (IHC) markers may provide more prognostic information than either classifier alone. EXPERIMENTAL DESIGN: We assessed Ki67 alone or combined with ER, PR and HER2 (forming IHC subtypes), and the research versions of the Genomic Grade Index (GGI), 70-gene, cell-cycle score (CCS), Recurrence Score (RS) and PAM50 signatures on matching TMA/whole tumour sections and microarray data in two Swedish breast cancer cohorts of 379 and 209 patients, with median follow-up of 12...
September 29, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28972041/pam50-provides-prognostic-information-when-applied-to-the-lymph-node-metastases-of-advanced-breast-cancer-patients
#9
Nicholas P Tobin, Arian Lundberg, Linda S Lindström, J Chuck Harrell, Theodoros Foukakis, Lena Carlsson, Zakaria Einbeigi, Barbro K Linderholm, Niklas Loman, Martin Malmberg, Mårten Fernö, Kamila Czene, Charles M Perou, Jonas Bergh, Thomas Hatschek
Purpose: Transcriptional pathway activity and the molecular subtypes of breast cancer metastases have been shown to significantly influence patient postrelapse survival. Here, we further determine the relevance of clinically employed gene signatures in the advanced breast cancer (ABC) setting.Experimental Design: Sufficient RNA for expression profiling was obtained from distant metastatic or inoperable loco-regional relapse tissue by fine-needle aspiration from 109 patients of the Swedish TEX clinical trial...
September 29, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28940389/assessment-of-early-response-biomarkers-in-relation-to-long-term-survival-in-patients-with-her2-negative-breast-cancer-receiving-neoadjuvant-chemotherapy-plus-bevacizumab-results-from-the-phase-2-promix-trial
#10
S Kimbung, I Markholm, J Bjöhle, T Lekberg, A von Wachenfeldt, E Azavedo, A Saracco, M Hellström, S Veerla, E Paquet, P O Bendahl, M Fernö, J Bergh, N Loman, T Hatschek, I Hedenfalk
Pathologic complete response (pCR) is a predictor for favorable outcome after neoadjuvant treatment in early breast cancer. Modulation of gene expression may also provide early readouts of biological activity and prognosis, offering the possibility for timely response-guided treatment adjustment. The role of early transcriptional changes in predicting response to neoadjuvant chemotherapy plus bevacizumab was investigated. One-hundred-and-fifty patients with large, operable and locally advanced HER2-negative breast cancer received epirubicin and docetaxel, with the addition of bevacizumab...
September 22, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28912426/deconvolution-of-dna-methylation-identifies-differentially-methylated-gene-regions-on-1p36-across-breast-cancer-subtypes
#11
Alexander J Titus, Gregory P Way, Kevin C Johnson, Brock C Christensen
Breast cancer is a complex disease consisting of four distinct molecular subtypes. DNA methylation-based (DNAm) studies in tumors are complicated further by disease heterogeneity. In the present study, we compared DNAm in breast tumors with normal-adjacent breast samples from The Cancer Genome Atlas (TCGA). We constructed models stratified by tumor stage and PAM50 molecular subtype and performed cell-type reference-free deconvolution to control for cellular heterogeneity. We identified nineteen differentially methylated gene regions (DMGRs) in early stage tumors across eleven genes (AGRN, C1orf170, FAM41C, FLJ39609, HES4, ISG15, KLHL17, NOC2L, PLEKHN1, SAMD11, WASH5P)...
September 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28878133/exome-capture-rna-sequencing-of-decade-old-breast-cancers-and-matched-decalcified-bone-metastases
#12
Nolan Priedigkeit, Rebecca J Watters, Peter C Lucas, Ahmed Basudan, Rohit Bhargava, William Horne, Jay K Kolls, Zhou Fang, Margaret Q Rosenzweig, Adam M Brufsky, Kurt R Weiss, Steffi Oesterreich, Adrian V Lee
Bone metastases (BoM) are a significant cause of morbidity in patients with estrogen receptor-positive (ER-positive) breast cancer; yet, characterizations of human specimens are limited. In this study, exome-capture RNA sequencing (ecRNA-seq) on aged (8-12 years), formalin-fixed, paraffin-embedded (FFPE), and decalcified cancer specimens was evaluated. Gene expression values and ecRNA-seq quality metrics from FFPE or decalcified tumor RNA showed minimal differences when compared with matched flash-frozen or nondecalcified tumors...
September 7, 2017: JCI Insight
https://www.readbyqxmd.com/read/28859291/relevance-of-spatial-heterogeneity-of-immune-infiltration-for-predicting-risk-of-recurrence-after-endocrine-therapy-of-er-breast-cancer
#13
Andreas Heindl, Ivana Sestak, Kalnisha Naidoo, Jack Cuzick, Mitchell Dowsett, Yinyin Yuan
Background: Despite increasing evidence supporting the clinical utility of immune infiltration in the estrogen receptor-negative (ER-) subtype, the prognostic value of immune infiltration for ER+ disease is not well defined. Methods: Quantitative immune scores of cell abundance and spatial heterogeneity were computed using a fully automated hematoxylin and eosin-stained image analysis algorithm and spatial statistics for 1178 postmenopausal patients with ER+ breast cancer treated with five years' tamoxifen or anastrozole...
February 1, 2018: Journal of the National Cancer Institute
https://www.readbyqxmd.com/read/28859290/racial-differences-in-pam50-subtypes-in-the-carolina-breast-cancer-study
#14
Melissa A Troester, Xuezheng Sun, Emma H Allott, Joseph Geradts, Stephanie M Cohen, Chiu-Kit Tse, Erin L Kirk, Leigh B Thorne, Michelle Mathews, Yan Li, Zhiyuan Hu, Whitney R Robinson, Katherine A Hoadley, Olufunmilayo I Olopade, Katherine E Reeder-Hayes, H Shelton Earp, Andrew F Olshan, Lisa A Carey, Charles M Perou
Background: African American breast cancer patients have lower frequency of hormone receptor-positive (HR+)/human epidermal growth factor receptor 2 (HER2)-negative disease and higher subtype-specific mortality. Racial differences in molecular subtype within clinically defined subgroups are not well understood. Methods: Using data and biospecimens from the population-based Carolina Breast Cancer Study (CBCS) Phase 3 (2008-2013), we classified 980 invasive breast cancers using RNA expression-based PAM50 subtype and recurrence (ROR) score that reflects proliferation and tumor size...
February 1, 2018: Journal of the National Cancer Institute
https://www.readbyqxmd.com/read/28629479/evaluation-of-invasive-breast-cancer-samples-using-a-12-chemokine-gene-expression-score-correlation-with-clinical-outcomes
#15
Sangeetha Prabhakaran, Victoria T Rizk, Zhenjun Ma, Chia-Ho Cheng, Anders E Berglund, Dominico Coppola, Farah Khalil, James J Mulé, Hatem H Soliman
BACKGROUND: A unique 12-chemokine gene expression score (CS) accurately predicted the presence of tumor-localized, ectopic lymph node-like structures (TL-ELNs) and improved overall survival (OS) in primary colorectal cancer and metastatic melanoma. We analyzed the correlation between CS, clinicopathological variables, molecular data, and 366 survival in Moffitt Cancer Center's Total Cancer Care (TCC) patients with non-metastatic breast cancer. METHODS: Affymetrix gene expression profiles were used to interrogate the CS by the principal component method...
June 19, 2017: Breast Cancer Research: BCR
https://www.readbyqxmd.com/read/28512241/assessment-of-breast-cancer-risk-factors-reveals-subtype-heterogeneity
#16
Johanna Holm, Louise Eriksson, Alexander Ploner, Mikael Eriksson, Mattias Rantalainen, Jingmei Li, Per Hall, Kamila Czene
Subtype heterogeneity for breast cancer risk factors has been suspected, potentially reflecting etiologic differences and implicating risk prediction. However, reports are conflicting regarding the presence of heterogeneity for many exposures. To examine subtype heterogeneity across known breast cancer risk factors, we conducted a case-control analysis of 2,632 breast cancers and 15,945 controls in Sweden. Molecular subtype was predicted from pathology record-derived IHC markers by a classifier trained on PAM50 subtyping...
July 1, 2017: Cancer Research
https://www.readbyqxmd.com/read/28510570/bag-1-as-a-biomarker-in-early-breast-cancer-prognosis-a-systematic-review-with-meta-analyses
#17
REVIEW
E S Papadakis, T Reeves, N H Robson, T Maishman, G Packham, R I Cutress
BACKGROUND: The co-chaperone protein Bcl-2-associated athanogene-1 (BAG-1) is overexpressed in breast cancer and has been incorporated in the oncotype DX and PAM50 breast cancer prognostic assays. Bcl-2-associated athanogene-1 exists as multiple protein isoforms that interact with diverse partners, including chaperones Hsc70/Hsp70, Ser/Thr kinase Raf-1 and Bcl-2, to promote cancer cell survival. The BAG-1L isoform specifically binds to and increases the transcriptional activity of oestrogen receptor in cells, and in some, but not all studies, BAG-1 expression is predictive of clinical outcome in breast cancer...
June 6, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28494073/associations-of-luminal-and-basal-subtyping-of-prostate-cancer-with-prognosis-and-response-to-androgen-deprivation-therapy
#18
Shuang G Zhao, S Laura Chang, Nicholas Erho, Menggang Yu, Jonathan Lehrer, Mohammed Alshalalfa, Corey Speers, Matthew R Cooperberg, Won Kim, Charles J Ryan, Robert B Den, Stephen J Freedland, Edwin Posadas, Howard Sandler, Eric A Klein, Peter Black, Roland Seiler, Scott A Tomlins, Arul M Chinnaiyan, Robert B Jenkins, Elai Davicioni, Ashley E Ross, Edward M Schaeffer, Paul L Nguyen, Peter R Carroll, R Jeffrey Karnes, Daniel E Spratt, Felix Y Feng
Importance: There is a clear need for a molecular subtyping approach in prostate cancer to identify clinically distinct subgroups that benefit from specific therapies. Objectives: To identify prostate cancer subtypes based on luminal and basal lineage and to determine associations with clinical outcomes and response to treatment. Design, Setting, and Participants: The PAM50 classifier was used to subtype 1567 retrospectively collected (median follow-up, 10 years) and 2215 prospectively collected prostate cancer samples into luminal- and basal-like subtypes...
May 11, 2017: JAMA Oncology
https://www.readbyqxmd.com/read/28423537/limitations-in-predicting-pam50-intrinsic-subtype-and-risk-of-relapse-score-with-ki67-in-estrogen-receptor-positive-her2-negative-breast-cancer
#19
Aranzazu Fernandez-Martinez, Tomás Pascual, Giuseppe Perrone, Serafin Morales, Juan de la Haba, Milagros González-Rivera, Patricia Galván, Francesca Zalfa, Michela Amato, Lucia Gonzalez, Miquel Prats, Federico Rojo, Luis Manso, Laia Paré, Immaculada Alonso, Joan Albanell, Ana Vivancos, Antonio González, Judit Matito, Sonia González, Pedro Fernandez, Barbara Adamo, Montserrat Muñoz, Margarita Viladot, Carme Font, Francisco Aya, Maria Vidal, Rosalía Caballero, Eva Carrasco, Vittorio Altomare, Giuseppe Tonini, Aleix Prat, Miguel Martin
PAM50/Prosigna gene expression-based assay identifies three categorical risk of relapse groups (ROR-low, ROR-intermediate and ROR-high) in post-menopausal patients with estrogen receptor estrogen receptor-positive (ER+)/ HER2-negative (HER2-) early breast cancer. Low risk patients might not need adjuvant chemotherapy since their risk of distant relapse at 10-years is below 10% with endocrine therapy only. In this study, 517 consecutive patients with ER+/HER2- and node-negative disease were evaluated for Ki67 and Prosigna...
March 28, 2017: Oncotarget
https://www.readbyqxmd.com/read/28376177/progesterone-receptor-isoform-ratio-a-breast-cancer-prognostic-and-predictive-factor-for-antiprogestin-responsiveness
#20
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
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