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
Citations
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Genomic and mutational profiling of ductal carcinomas in situ and matched adjacent invasive breast cancers reveals intra-tumour genetic heterogeneity and clonal selection
Lucia Hernandez,Paul M. Wilkerson,Maryou B. Lambros,Adriana Campion-Flora,Daniel Nava Rodrigues,Arnaud Gauthier,Arnaud Gauthier,Cecilia Cabral,Vidya Pawar,Alan Mackay,Roger A'Hern,Caterina Marchiò,J Palacios,Rachael Natrajan,Britta Weigelt,Britta Weigelt,Jorge S. Reis-Filho +16 more
TL;DR: Despite the genomic similarities between synchronous DCIS and IDC, the data provide strong circumstantial evidence to suggest that in some cases the progression from DCIS to IDC is driven by the selection of non‐modal clones that harbour a specific repertoire of genetic aberrations.
Journal ArticleDOI
Tackling the Diversity of Triple-Negative Breast Cancer
TL;DR: A diverse set of genetic events have been described in TNBC, with a number of potentially targetable genetic events found although all at relatively low frequency, and clinical trials to define the clinical utility of therapies targeting these low-frequency events will require substantial screening efforts to identify sufficient patients.
Journal ArticleDOI
An Update on Breast Cancer Multigene Prognostic Tests-Emergent Clinical Biomarkers.
TL;DR: Comparing the molecular tests OncotypeDX, MammaPrint, Prosigna, EndoPredict, Breast Cancer Index, Mammostrat, and IHC4 and report the eligibility of each one in the suitable setting, triple negative carcinomas are very heterogeneous regarding prognosis and new molecular signatures that decipher thisvery heterogeneous subgroup of breast cancer may improve the clinical management of the disease.
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Genome organizing function of SATB1 in tumor progression.
Terumi Kohwi-Shigematsu,Krzysztof Poterlowicz,Ellen Ordinario,Hye-Jung Han,Vladimir A. Botchkarev,Yoshinori Kohwi +5 more
TL;DR: SATB1 is a genome organizer protein that facilitates these processes, providing a nuclear architectural platform that anchors hundreds of genes, through its interaction with specific genomic sequences, and its role in metastasis of breast cancer and other tumor types is described.
Journal ArticleDOI
MiRNA-621 sensitizes breast cancer to chemotherapy by suppressing FBXO11 and enhancing p53 activity.
Jingyan Xue,Jingyan Xue,Yayun Chi,Yu Chen,Yu Chen,Shi Huang,X. Ye,Jixiao Niu,Wei Wang,Lawrence M. Pfeffer,Z. M. Shao,Zhao-Hui Wu,Jiong Wu +12 more
TL;DR: It is suggested that miR-621 enhances chemosensitivity of breast cancer cells to PTX/CBP chemotherapy by suppressing FBXO11-depedent inhibition of p53 and may serve as a predictive biomarker and a potential therapeutic target in breast cancer treatment.
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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