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Cancer research, Vol. 69, No. 9. (1 May 2009), pp. 3795-3801.
Abstract
We have analyzed the DNA copy numbers for over 100,000 single-nucleotide polymorphism loci across the human genome in genomic DNA from 313 lymph node-negative primary breast tumors for which genome-wide gene expression data were also available. Combining these two data sets allowed us to identify the genomic loci and their mapped genes, having high correlation with distant metastasis. An estimation of the likely response based on published predictive signatures was performed in the identified prognostic subgroups defined by gene expression and ...
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Breast cancer research and treatment (19 April 2008)
by Chad J. Creighton, C Kent Osborne, Marc J. van de Vijver, et al.John A. Foekens, Jan G. Klijn, Hugo M. Horlings, Dimitry Nuyten, Yixin Wang, Yi Zhang, Gary C. Chamness, Susan G. Hilsenbeck, Adrian V. Lee, Rachel Schiff
Abstract
Background Patient prognosis and response to endocrine therapy in breast cancer correlate with protein expression of both estrogen receptor (ER) and progesterone receptor (PR), with poorer outcome in patients with ER+/PR- compared to ER+/PR+ tumors. Methods To better understand the underlying biology of ER+/PR- tumors, we examined RNA expression (n > 1000 tumors) and DNA copy number profiles from five previously published studies of human breast cancers with clinically assigned hormone receptor status (ER+/PR+, ER+/PR-, and ER-/PR-). Results We identified an ...
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PLoS genetics, Vol. 4, No. 4. (April 2008)
by M. Garcia-Closas, P. Hall, H. Nevanlinna, et al.K. Pooley, J. Morrison, D. A. Richesson, S. E. Bojesen, B. G. Nordestgaard, C. K. Axelsson, J. I. Arias, R. L. Milne, G. Ribas, A. González-Neira, J. Benítez, P. Zamora, H. Brauch, C. Justenhoven, U. Hamann, Y. D. Ko, T. Bruening, S. Haas, T. Dörk, P. Schürmann, P. Hillemanns, N. Bogdanova, M. Bremer, J. H. Karstens, R. Fagerholm, K. Aaltonen, K. Aittomäki, K. von Smitten, C. Blomqvist, A. Mannermaa, M. Uusitupa, M. Eskelinen, M. Tengström, V. M. Kosma, V. Kataja, G. Chenevix-Trench, A. B. Spurdle, J. Beesley, X. Chen, Australian Ovarian Cancer Management Group, Kathleen Cuningham Foundation Consortium For Research Into Familial Breast Cancer, P. Devilee, C. J. van Asperen, C. E. Jacobi, R. A. Tollenaar, P. E. Huijts, J. G. Klijn, J. Chang-Claude, S. Kropp, T. Slanger, D. Flesch-Janys, E. Mutschelknauss, R. Salazar, S. Wang-Gohrke, F. Couch, E. L. Goode, J. E. Olson, C. Vachon, Z. S. Fredericksen, G. G. Giles, L. Baglietto, G. Severi, J. L. Hopper, D. R. English, M. C. Southey, C. A. Haiman, B. E. Henderson, L. N. Kolonel, L. Le Marchand, D. O. Stram, D. J. Hunter, S. E. Hankinson, D. G. Cox, R. Tamimi, P. Kraft, M. E. Sherman, S. J. Chanock, J. Lissowska, L. A. Brinton, B. Peplonska, J. G. Klijn, M. J. Hooning, H. Meijers-Heijboer, J. M. Collee, A. van den Ouweland, A. G. Uitterlinden, J. Liu, L. Y. Lin, L. Yuqing, K. Humphreys, K. Czene, A. Cox, S. P. Balasubramanian, S. S. Cross, M. W. Reed, F. Blows, K. Driver, A. Dunning, J. Tyrer, B. A. Ponder, S. Sangrajrang, P. Brennan, J. McKay, F. Odefrey, V. Gabrieau, A. Sigurdson, M. Doody, J. P. Struewing, B. Alexander, D. F. Easton, P. D. Pharoah
Abstract
A three-stage genome-wide association study recently identified single nucleotide polymorphisms (SNPs) in five loci (fibroblast growth receptor 2 (FGFR2), trinucleotide repeat containing 9 (TNRC9), mitogen-activated protein kinase 3 K1 (MAP3K1), 8q24, and lymphocyte-specific protein 1 (LSP1)) associated with breast cancer risk. We investigated whether the associations between these SNPs and breast cancer risk varied by clinically important tumor characteristics in up to 23,039 invasive breast cancer cases and 26,273 controls from 20 studies. We also evaluated their influence on overall survival ...
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Proceedings of the National Academy of Sciences of the United States of America, Vol. 105, No. 35. (2 September 2008), pp. 13021-13026.
Abstract
In this study, we quantified 249 mature micro-RNA (miRNA) transcripts in estrogen receptor-positive (ER(+)) primary breast tumors of patients with lymph node-negative (LNN) disease to identify miRNAs associated with metastatic capability. In addition, the prognostic value of the candidate miRNAs was determined in ER(-)/LNN breast cancer. Unsupervised analysis in a prescreening set of 38 patients identified three subgroups predominantly driven by three miRNA signatures: an ER-driven luminal B-associated miRNA signature, a stromal miRNA signature, and an overexpressed miRNA cluster located on ...
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Drug discovery today, Vol. 13, No. 11-12. (June 2008), pp. 481-487.
Abstract
The use of gene-expression microarray analysis to assess the expression levels of all the genes in the genome has tremendous potential. Important information has been obtained about many disease processes, particularly in classifying tumors in different subtypes and risk groups. Combining gene-expression data with other genomic information and the use of sophisticated bioinformatic tools enables the discovery of potential new targets for treatment, and is helpful for high-throughput drug screening and for designing new classes of drugs for targeted therapy. Here, ...
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BMC cancer, Vol. 7, No. 1. (25 September 2007), 182.
Abstract
BACKGROUND: Published prognostic gene signatures in breast cancer have few genes in common. Here we provide a rationale for this observation by studying the prognostic power and the underlying biological pathways of different gene signatures. METHODS: Gene signatures to predict the development of metastases in estrogen receptor-positive and estrogen receptor-negative tumors were identified using 500 re-sampled training sets and mapping to Gene Ontology Biological Process to identify over-represented pathways. The Global Test program confirmed that gene expression profilings in the common ...
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Breast cancer research and treatment, Vol. 113, No. 2. (4 January 2009), pp. 275-283.
by M. Kok, S. C. Linn, R. K. Van Laar, et al.M. P. Jansen, T. M. van den Berg, L. J. Delahaye, A. M. Glas, J. L. Peterse, M. Hauptmann, J. A. Foekens, J. G. Klijn, L. F. Wessels, L. J. Van't Veer, E. M. Berns
Abstract
BACKGROUND: Molecular signatures that predict outcome in tamoxifen treated breast cancer patients have been identified. For the first time, we compared these response profiles in an independent cohort of (neo)adjuvant systemic treatment naïve breast cancer patients treated with first-line tamoxifen for metastatic disease. METHODS: From a consecutive series of 246 estrogen receptor (ER) positive primary tumors, gene expression profiling was performed on available frozen tumors using 44K oligoarrays (n = 69). A 78-gene tamoxifen response profile (formerly consisting of 81 cDNA-clones), ...
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Cancer research, Vol. 68, No. 9. (1 May 2008), pp. 3108-3114.
Abstract
We explored whether the five previously reported molecular subtypes in breast cancer show a preference for organ-specific relapse and searched for molecular pathways involved. The "intrinsic" gene list describing the subtypes was used to classify 344 primary breast tumors of lymph node-negative patients. Fisher exact tests were used to determine the association between a tumor subtype and a particular site of distant relapse in these patients who only received local treatment. Modulated genes and pathways were identified in the various groups ...
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J Clin Oncol, Vol. 24, No. 15. (20 May 2006), pp. 2261-2267.
Abstract
PURPOSE: The biology of tumors relapsing to bone is poorly understood. In this study, we initiated a search for genes that are implicated in tumors relapsing to bone in breast cancer. PATIENTS AND METHODS: We analyzed 107 primary breast tumors in patients who were all lymph node negative at the time of diagnosis and all had experienced relapse. Total RNA isolated from frozen tumor samples was used to gather gene expression data using oligo microarrays. RESULTS: A panel of 69 genes ...
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Clinical cancer research : an official journal of the American Association for Cancer Research, Vol. 13, No. 11. (1 June 2007), pp. 3207-3214.
by Christine Desmedt, Fanny Piette, Sherene Loi, et al.Yixin Wang, Françoise Lallemand, Benjamin Haibe-Kains, Giuseppe Viale, Mauro Delorenzi, Yi Zhang, Mahasti Saghatchian S. d'Assignies, Jonas Bergh, Rosette Lidereau, Paul Ellis, Adrian L. Harris, Jan G. Klijn, John A. Foekens, Fatima Cardoso, Martine J. Piccart, Marc Buyse, Christos Sotiriou, TRANSBIG Consortium
Abstract
PURPOSE: Recently, a 76-gene prognostic signature able to predict distant metastases in lymph node-negative (N(-)) breast cancer patients was reported. The aims of this study conducted by TRANSBIG were to independently validate these results and to compare the outcome with clinical risk assessment. EXPERIMENTAL DESIGN: Gene expression profiling of frozen samples from 198 N(-) systemically untreated patients was done at the Bordet Institute, blinded to clinical data and independent of Veridex. Genomic risk was defined by Veridex, blinded to clinical data. ...
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Nature (27 May 2007)
by Douglas F. Easton, Karen A. Pooley, Alison M. Dunning, et al.Paul D. P. Pharoah, Deborah Thompson, Dennis G. Ballinger, Jeffery P. Struewing, Jonathan Morrison, Helen Field, Robert Luben, Nicholas Wareham, Shahana Ahmed, Catherine S. Healey, Richard Bowman, Kerstin B. Meyer, Christopher A. Haiman, Laurence K. Kolonel, Brian E. Henderson, Loic Le Marchand, Paul Brennan, Suleeporn Sangrajrang, Valerie Gaborieau, Fabrice Odefrey, Chen-Yang Shen, Pei-Ei Wu, Hui-Chun Wang, Diana Eccles, Gareth D. Evans, Julian Peto, Olivia Fletcher, Nichola Johnson, Sheila Seal, Michael R. Stratton, Nazneen Rahman, Georgia Chenevix-Trench, Stig E. Bojesen, Børge G. Nordestgaard, Christen K. Axelsson, Montserrat Garcia-Closas, Louise Brinton, Stephen Chanock, Jolanta Lissowska, Beata Peplonska, Heli Nevanlinna, Rainer Fagerholm, Hannaleena Eerola, Daehee Kang, Keun-Young Yoo, Dong-Young Noh, Sei-Hyun Ahn, David J. Hunter, Susan E. Hankinson, David G. Cox, Per Hall, Sara Wedren, Jianjun Liu, Yen-Ling Low, Natalia Bogdanova, Peter Schürmann, Thilo Dörk, Rob A. E. M. Tollenaar, Catharina E. Jacobi, Peter Devilee, Jan G. M. Klijn, Alice J. Sigurdson, Michele M. Doody, Bruce H. Alexander, Jinghui Zhang, Angela Cox, Ian W. Brock, Gordon Macpherson, Malcolm W. R. Reed, Fergus J. Couch, Ellen L. Goode, Janet E. Olson, Hanne Meijers-Heijboer, Ans van den Ouweland, André Uitterlinden, Fernando Rivadeneira, Roger L. Milne, Gloria Ribas, Anna Gonzalez-Neira, Javier Benitez, John L. Hopper, Margaret Mccredie, Melissa Southey, Graham G. Giles, Chris Schroen, Christina Justenhoven, Hiltrud Brauch, Ute Hamann, Yon-Dschun Ko, Amanda B. Spurdle, Jonathan Beesley, Xiaoqing Chen, Arto Mannermaa, Veli-Matti Kosma, Vesa Kataja, Jaana Hartikainen, Nicholas E. Day, David R. Cox, Bruce A. J. Ponder
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J Clin Oncol, Vol. 25, No. 10. (1 April 2007), pp. 1239-1246.
by Sherene Loi, Benjamin Haibe-Kains, Christine Desmedt, et al.Francoise Lallemand, Andrew M. Tutt, Cheryl Gillet, Paul Ellis, Adrian Harris, Jonas Bergh, John A. Foekens, Jan G. M. Klijn, Denis Larsimont, Marc Buyse, Gianluca Bontempi, Mauro Delorenzi, Martine J. Piccart, Christos Sotiriou
Abstract
PurposeA number of microarray studies have reported distinct molecular profiles of breast cancers (BC), such as basal-like, ErbB2-like, and two to three luminal-like subtypes. These were associated with different clinical outcomes. However, although the basal and the ErbB2 subtypes are repeatedly recognized, identification of estrogen receptor (ER) -positive subtypes has been inconsistent. Therefore, refinement of their molecular definition is needed. Materials and MethodsWe have previously reported a gene expression grade index (GGI), which defines histologic grade based on gene expression ...
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J Clin Oncol, Vol. 25, No. 6. (20 February 2007), pp. 662-668.
Abstract
PURPOSE: A HOXB13-to-IL17BR expression ratio was previously identified to predict clinical outcome of breast cancer patients treated with adjuvant tamoxifen. However, this ratio may predict a tumor's response to tamoxifen, its intrinsic aggressiveness, or both. PATIENTS AND METHODS: We have measured the HOXB13 and IL17BR expression levels by real-time polymerase chain reaction in 1,252 primary breast tumor specimens. Expression levels were normalized to housekeeper gene levels and related to clinicopathologic factors for all patients. The primary objective of this study was ...
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Br J Cancer, Vol. 85, No. 4. (17 August 2001), pp. 538-545.
Abstract
About 5-10% of breast cancers are hereditary; a genetically and clinically heterogeneous disease in which several susceptibility genes, including BRCA1, have been identified. While distinct tumour features can be used to estimate the likelihood that a breast tumour is caused by a BRCA1 germline mutation it is not yet possible to categorize a BRCA1 mutated tumour. The aim of the present study is to molecularly classify BRCA1 mutated breast cancers by resolving gene expression patterns of BRCA1 and matched sporadic surgical ...
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Clin Cancer Res, Vol. 11, No. 14. (15 July 2005), pp. 5175-5180.
by Sunil R. Lakhani, Jorge S. Reis-Filho, Laura Fulford, et al.Frederique Penault-Llorca, Marc van der Vijver, Suzanne Parry, Timothy Bishop, Javier Benitez, Carmen Rivas, Yves-Jean Bignon, Jenny Chang-Claude, Ute Hamann, Cees J. Cornelisse, Peter Devilee, Matthias W. Beckmann, Carolin Nestle-Kramling, Peter A. Daly, Neva Haites, Jenny Varley, Fiona Lalloo, Gareth Evans, Christine Maugard, Hanne Meijers-Heijboer, Jan G. Klijn, Edith Olah, Barry A. Gusterson, Silvana Pilotti, Paolo Radice, Siegfried Scherneck, Hagay Sobol, Jocelyne Jacquemier, Teresa Wagner, Julian Peto, Michael R. Stratton, Lesley Mcguffog, Douglas F. Easton, The
Abstract
Purpose: To investigate the proportion of breast cancers arising in patients with germ line BRCA1 and BRCA2 mutations expressing basal markers and developing predictive tests for identification of high-risk patients. Experimental Design: Histopathologic material from 182 tumors in BRCA1 mutation carriers, 63 BRCA2 carriers, and 109 controls, collected as part of the international Breast Cancer Linkage Consortium were immunohistochemically stained for CK14, CK5/6, CK17, epidermal growth factor receptor (EGFR), and osteonectin. Results: All five basal markers were commoner in ...
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Oncogene, Vol. aop, No. current.
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Lancet, Vol. 365, No. 9460. (5 2005), pp. 671-679.
by Yixin Wang, Jan G. Klijn, Yi Zhang, et al.Anieta M. Sieuwerts, Maxime P. Look, Fei Yang, Dmitri Talantov, Mieke Timmermans, Marion E. Meijer-van Gelder, Jack Yu, Tim Jatkoe, Els M. Berns, David Atkins, John A. Foekens
Abstract
BACKGROUND: Genome-wide measures of gene expression can identify patterns of gene activity that subclassify tumours and might provide a better means than is currently available for individual risk assessment in patients with lymph-node-negative breast cancer. METHODS: We analysed, with Affymetrix Human U133a GeneChips, the expression of 22000 transcripts from total RNA of frozen tumour samples from 286 lymph-node-negative patients who had not received adjuvant systemic treatment. FINDINGS: In a training set of 115 tumours, we identified a 76-gene signature consisting of ...
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