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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Cancer stem cell-driven efficacy of trastuzumab (Herceptin): towards a reclassification of clinically HER2-positive breast carcinomas.
Begoña Martin-Castillo,Eugeni López-Bonet,Elisabet Cuyàs,Gemma Viñas,Sonia Pernas,Joan Dorca,Javier A. Menendez +6 more
TL;DR: Contrary to the current dichotomous model used clinically, this model proposes that a reclassification of cHER2+ tumors based on the spectrum of molecular BC subtypes might inform on their CSC-determined sensitivity to trastuzumab, thus providing a better delineation of the predictive value of c HER2+ in BC by incorporating CSCs-driven intra-tumor heterogeneity into clinical decisions.
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Prognostic Value of Ki-67 in Patients With Resected Triple-Negative Breast Cancer: A Meta-Analysis.
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New Advances in Molecular Breast Cancer Pathology.
Emad A. Rakha,Fresia Pareja +1 more
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Individualized therapy for metastatic colorectal cancer.
Alessandra Silvestri,Elisa Pin,Anne Huijbers,R. Pellicani,E.V. Parasido,M. Pierobon,E. Petricoin,Lance A. Liotta,Claudio Belluco +8 more
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Gene expression profiling to dissect the complexity of cancer biology: Pitfalls and promise
TL;DR: It is concluded that while high throughput technologies developed to determine gene expression profiles potentially offer an effective tool for dissecting the biology of cancer pathologies, there are limitations to their use in understanding cancer biology and in routine clinical application.
References
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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
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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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