A pathway-based classification of human breast cancer.

Published

Journal Article

The hallmark of human cancer is heterogeneity, reflecting the complexity and variability of the vast array of somatic mutations acquired during oncogenesis. An ability to dissect this heterogeneity, to identify subgroups that represent common mechanisms of disease, will be critical to understanding the complexities of genetic alterations and to provide a framework to develop rational therapeutic strategies. Here, we describe a classification scheme for human breast cancer making use of patterns of pathway activity to build on previous subtype characterizations using intrinsic gene expression signatures, to provide a functional interpretation of the gene expression data that can be linked to therapeutic options. We show that the identified subgroups provide a robust mechanism for classifying independent samples, identifying tumors that share patterns of pathway activity and exhibit similar clinical and biological properties, including distinct patterns of chromosomal alterations that were not evident in the heterogeneous total population of tumors. We propose that this classification scheme provides a basis for understanding the complex mechanisms of oncogenesis that give rise to these tumors and to identify rational opportunities for combination therapies.

Full Text

Duke Authors

Cited Authors

  • Gatza, ML; Lucas, JE; Barry, WT; Kim, JW; Wang, Q; Crawford, MD; Datto, MB; Kelley, M; Mathey-Prevot, B; Potti, A; Nevins, JR

Published Date

  • April 2010

Published In

Volume / Issue

  • 107 / 15

Start / End Page

  • 6994 - 6999

PubMed ID

  • 20335537

Pubmed Central ID

  • 20335537

Electronic International Standard Serial Number (EISSN)

  • 1091-6490

International Standard Serial Number (ISSN)

  • 0027-8424

Digital Object Identifier (DOI)

  • 10.1073/pnas.0912708107

Language

  • eng