title: A cell proliferation signature is a marker of extremely poor outcome in a subpopulation of breast cancer patients.
abstract: Breast cancer comprises a group of distinct subtypes that despite having similar histologic appearances, have very different metastatic potentials. Being able to identify the biological driving force, even for a subset of patients, is crucially important given the large population of women diagnosed with breast cancer. Here, we show that within a subset of patients characterized by relatively high estrogen receptor expression for their age, the occurrence of metastases is strongly predicted by a homogeneous gene expression pattern almost entirely consisting of cell cycle genes (5-year odds ratio of metastasis, 24.0; 95% confidence interval, 6.0-95.5). Overexpression of this set of genes is clearly associated with an extremely poor outcome, with the 10-year metastasis-free probability being only 24% for the poor group, compared with 85% for the good group. In contrast, this gene expression pattern is much less correlated with the outcome in other patient subpopulations. The methods described here also illustrate the value of combining clinical variables, biological insight, and machine-learning to dissect biological complexity. Our work presented here may contribute a crucial step towards rational design of personalized treatment.
authors.affiliation: Rosetta Inpharmatics LLC, (A wholly owned subsidiary of Merck & Co. Inc.) Seattle, Washington, USA.
authors.forename: Hongyue
authors.initials: H
authors.lastname: Dai
authors.forename: Laura
authors.initials: L
authors.lastname: van't Veer
authors.forename: John
authors.initials: J
authors.lastname: Lamb
authors.forename: Yudong D
authors.initials: YD
authors.lastname: He
authors.forename: Mao
authors.initials: M
authors.lastname: Mao
authors.forename: Bernard M
authors.initials: BM
authors.lastname: Fine
authors.forename: Rene
authors.initials: R
authors.lastname: Bernards
authors.forename: Marc
authors.initials: M
authors.lastname: van de Vijver
authors.forename: Paul
authors.initials: P
authors.lastname: Deutsch
authors.forename: Alan
authors.initials: A
authors.lastname: Sachs
authors.forename: Roland
authors.initials: R
authors.lastname: Stoughton
authors.forename: Stephen
authors.initials: S
authors.lastname: Friend
mesh_terms: D000367:Age Factors; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D002453:Cell Cycle / Q000235:genetics; D048708:Cell Growth Processes / Q000235:genetics; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D009362:Neoplasm Metastasis; D020411:Oligonucleotide Array Sequence Analysis; D011379:Prognosis; D011960:Receptors, Estrogen / Q000096:biosynthesis / Q000235:genetics
chemical_list: D011960:Receptors, Estrogen