Journal ArticleDOI
Challenges translating breast cancer gene signatures into the clinic
TLDR
The hurdles in the development and validation of molecular classification systems, and prognostic and predictive signatures based on microarray gene-expression profiling are discussed and it is suggested that similar challenges are likely to be encountered in translating next-generation sequencing data into clinically useful information.Abstract:
The advent of microarray-based gene-expression profiling a decade ago raised high expectations for rapid advances in breast cancer classification, prognostication and prediction. Despite the development of molecular classifications, and prognostic and predictive gene-expression signatures, microarray-based studies have not yielded definitive answers to many of the questions that remain germane for the successful implementation of personalized medicine. There are a lack of robust signatures to predict benefit from specific therapeutic agents and it is still not possible to predict prognosis or chemotherapy treatment response in specific disease subsets accurately, such as triple-negative breast cancer. We discuss the hurdles in the development and validation of molecular classification systems, and prognostic and predictive signatures based on microarray gene-expression profiling. We suggest that similar challenges are likely to be encountered in translating next-generation sequencing data into clinically useful information. Finally we highlight strategies for the development of clinically useful molecular predictors in the future.read more
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Whole transcriptome RNA-Seq analysis of breast cancer recurrence risk using formalin-fixed paraffin-embedded tumor tissue
Dominick Sinicropi,Kunbin Qu,Francois Collin,Michael Crager,Mei-Lan Liu,Robert J. Pelham,Mylan Pho,Andrew Dei Rossi,Jennie Jeong,Aaron Scott,Ranjana Ambannavar,Christina Zheng,Raúl Mena,José A. Esteban,James C. Stephans,John Morlan,Joffre B. Baker +16 more
TL;DR: This work has developed and optimized RNA-Seq library chemistry as well as bioinformatics and biostatistical methods for whole transcriptome profiling from FFPE tissue, which enable rediscovery of RNA biomarkers for disease recurrence risk that were previously identified by RT-PCR analysis of a cohort of 136 patients and identifies a high percentage of recurrencerisk markers previously discovered using DNA microarrays.
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RB-Pathway Disruption Is Associated with Improved Response to Neoadjuvant Chemotherapy in Breast Cancer
Agnieszka K. Witkiewicz,Adam Ertel,Jeanne M. McFalls,Matias E. Valsecchi,Gordon F. Schwartz,Erik S. Knudsen +5 more
TL;DR: The data indicate that RB status is associated with the response to neoadjuvant chemotherapy in breast cancer and could be used to inform treatment, with similar results observed with multiple chemotherapy regimens.
Journal ArticleDOI
Multigene assays for classification, prognosis, and prediction in breast cancer: a critical review on the background and clinical utility
Peter Sinn,Sebastian Aulmann,Ralph M. Wirtz,Sarah Schott,F Marmé,Zsuzsanna Varga,Annette Lebeau,H.H. Kreipe,Andreas Schneeweiss +8 more
TL;DR: Gene signatures which are based on multigene profiling assays have been developed to better define the prognosis and prediction of therapy results in early-stage breast cancer and the current evidence of their clinical use is discussed.
Journal ArticleDOI
Breast cancer intratumor genetic heterogeneity: causes and implications
TL;DR: The impact of intratumor heterogeneity on response and resistance to therapy is beginning to be understood; this information may prove crucial for the potentials of personalized medicine to be realized.
Journal ArticleDOI
Expression and methylation patterns partition luminal-A breast tumors into distinct prognostic subgroups
TL;DR: The analysis of molecular classification of breast tumors using both expression and methylation data obtained from The Cancer Genome Atlas provides two prognostic gene sets that dissect and explain tumor variability within the luminal-A subgroup, thus, contributing to the advancement of subtype-specific diagnosis and treatment.
References
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Charles M. Perou,Therese Sørlie,Michael B. Eisen,Matt van de Rijn,Stefanie S. Jeffrey,Christian A. Rees,Jonathan R. Pollack,Douglas T. Ross,Hilde Johnsen,Lars A. Akslen,Øystein Fluge,Alexander Pergamenschikov,Cheryl A. Williams,Shirley Zhu,Per Eystein Lønning,Anne Lise Børresen-Dale,Patrick O. Brown,David Botstein +17 more
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Distinct types of diffuse large B-cell lymphoma identified by gene expression profiling
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Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: an overview of the randomised trials
O. Abe,R. Abe,K. Enomoto,K. Kikuchi,H. Koyama,H. Masuda,Y. Nomura,K. Sakai,K. Sugimachi,T. Tominaga,J. Uchino,M. Yoshida,J. L. Haybittle,C Davies,V. J. Harvey,T. M. Holdaway,R. G. Kay,B. H. Mason,John F. Forbes,Nicholas Wilcken,M. Gnant,Raimund Jakesz,M. Ploner,H. M. A. Yosef,C. Focan,J. P. Lobelle,U. Peek,G. D. Oates,Janet T. Powell,M. Durand,L. Mauriac,A. Di Leo,Stella Dolci,M.J. Piccart,M. B. Masood,D. Parker,J. J. Price,Pierre Hupperets,Sue Jackson,Joseph Ragaz,Donna L. Berry,Gloria Broadwater,C. Cirrincione,Hyman B. Muss,Larry Norton,Raymond B. Weiss,H. Abu-Zahra,S. M. Portnoj,Michael J. Baum,Jack Cuzick,Joan Houghton,David Riley,N. H. Gordon,H. L. Davis,A. Beatrice,J. Mihura,A. Naja,Y. Lehingue,P. Romestaing,J. B. Dubois,Thierry Delozier,J. Mace-Lesec'h,P. Rambert,O. Andrysek,J. Barkmanova,Julie Owen,P. Meier,A Howell,G. C. Ribeiro,R. Swindell,R Alison,J Boreham,Matthew Clarke,Rory Collins,Sarah C. Darby,P. Elphinstone,Vaughan Evans,Jon Godwin,Richard Gray,C. S. Harwood,C. 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Hercbergs,M Yoshimoto,Gerrit DeBoer,Alexander H.G. Paterson,JW Meakin,T. Panzarella,Y. Shan,Y. F. Shao,X. Wang,D. B. Zhao,Z. M. Chen,H. C. Pan,J. Bahi,M. Reid,M. Spittle,G. P. Deutsch,F. Senanayake,D. L. W. Kwong,Angelo Raffaele Bianco,Chiara Carlomagno,M. De Laurentiis,S. De Placido,Aman U. Buzdar,Tae C Smith,Jonas Bergh,Lars Holmberg,Göran Liljegren,Jan Nilsson,M. Seifert,P. Sevelda,C. C. Zielinsky,R. B. Buchanan,M. Cross,G.T. Royle,Janet A. Dunn,Robert Kerrin Hills,Michael Lee,J. M. Morrison,D. Spooner,A. Litton,Rowan T. Chlebowski,H. Caffier +412 more
TL;DR: The 10-year and 15-year effects of various systemic adjuvant therapies on breast cancer recurrence and survival are reported and it is found that the cumulative reduction in mortality is more than twice as big at 15 years as at 5 years after diagnosis.
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