Classification and risk stratification of invasive breast carcinomas using a real-time quantitative RT-PCR assay View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2006-04-20

AUTHORS

Laurent Perreard, Cheng Fan, John F Quackenbush, Michael Mullins, Nicholas P Gauthier, Edward Nelson, Mary Mone, Heidi Hansen, Saundra S Buys, Karen Rasmussen, Alejandra Ruiz Orrico, Donna Dreher, Rhonda Walters, Joel Parker, Zhiyuan Hu, Xiaping He, Juan P Palazzo, Olufunmilayo I Olopade, Aniko Szabo, Charles M Perou, Philip S Bernard

ABSTRACT

IntroductionPredicting the clinical course of breast cancer is often difficult because it is a diverse disease comprised of many biological subtypes. Gene expression profiling by microarray analysis has identified breast cancer signatures that are important for prognosis and treatment. In the current article, we use microarray analysis and a real-time quantitative reverse-transcription (qRT)-PCR assay to risk-stratify breast cancers based on biological 'intrinsic' subtypes and proliferation.MethodsGene sets were selected from microarray data to assess proliferation and to classify breast cancers into four different molecular subtypes, designated Luminal, Normal-like, HER2+/ER-, and Basal-like. One-hundred and twenty-three breast samples (117 invasive carcinomas, one fibroadenoma and five normal tissues) and three breast cancer cell lines were prospectively analyzed using a microarray (Agilent) and a qRT-PCR assay comprised of 53 genes. Biological subtypes were assigned from the microarray and qRT-PCR data by hierarchical clustering. A proliferation signature was used as a single meta-gene (log2 average of 14 genes) to predict outcome within the context of estrogen receptor status and biological 'intrinsic' subtype.ResultsWe found that the qRT-PCR assay could determine the intrinsic subtype (93% concordance with microarray-based assignments) and that the intrinsic subtypes were predictive of outcome. The proliferation meta-gene provided additional prognostic information for patients with the Luminal subtype (P = 0.0012), and for patients with estrogen receptor-positive tumors (P = 3.4 × 10-6). High proliferation in the Luminal subtype conferred a 19-fold relative risk of relapse (confidence interval = 95%) compared with Luminal tumors with low proliferation.ConclusionA real-time qRT-PCR assay can recapitulate microarray classifications of breast cancer and can risk-stratify patients using the intrinsic subtype and proliferation. The proliferation meta-gene offers an objective and quantitative measurement for grade and adds significant prognostic information to the biological subtypes. More... »

PAGES

r23

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URI

http://scigraph.springernature.com/pub.10.1186/bcr1399

DOI

http://dx.doi.org/10.1186/bcr1399

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1000603711

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/16626501


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373 grid-institutes:grid.429361.b schema:alternateName Department of Clinical Genetics, Maine Center for Cancer Medicine, Scarborough, Maine, USA
374 schema:name Department of Clinical Genetics, Maine Center for Cancer Medicine, Scarborough, Maine, USA
375 rdf:type schema:Organization
376 grid-institutes:grid.479969.c schema:alternateName Department of Oncological Sciences, Huntsman Cancer Institute, Utah, SLC, USA
377 schema:name Department of Oncological Sciences, Huntsman Cancer Institute, Utah, SLC, USA
378 rdf:type schema:Organization
379 grid-institutes:grid.516137.7 schema:alternateName Department of Genetics and Department of Pathology & Laboratory Sciences, Lineberger Comprehensive Cancer Center, University of North Carolina, North Carolina, Chapel Hill, USA
380 schema:name Department of Genetics and Department of Pathology & Laboratory Sciences, Lineberger Comprehensive Cancer Center, University of North Carolina, North Carolina, Chapel Hill, USA
381 rdf:type schema:Organization
 




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