title: Gene expression variation to predict 10-year survival in lymph-node-negative breast cancer.
abstract: BACKGROUND
  It is of great significance to find better markers to correctly distinguish between high-risk and low-risk breast cancer patients since the majority of breast cancer cases are at present being overtreated.
  
  
  METHODS
  46 tumours from node-negative breast cancer patients were studied with gene expression microarrays. A t-test was carried out in order to find a set of genes where the expression might predict clinical outcome. Two classifiers were used for evaluation of the gene lists, a correlation-based classifier and a Voting Features Interval (VFI) classifier. We then evaluated the predictive accuracy of this expression signature on tumour sets from two similar studies on lymph-node negative patients. They had both developed gene expression signatures superior to current methods in classifying node-negative breast tumours. These two signatures were also tested on our material.
  
  
  RESULTS
  A list of 51 genes whose expression profiles could predict clinical outcome with high accuracy in our material (96% or 89% accuracy in cross-validation, depending on type of classifier) was developed. When tested on two independent data sets, the expression signature based on the 51 identified genes had good predictive qualities in one of the data sets (74% accuracy), whereas their predictive value on the other data set were poor, presumably due to the fact that only 23 of the 51 genes were found in that material. We also found that previously developed expression signatures could predict clinical outcome well to moderately well in our material (72% and 61%, respectively).
  
  
  CONCLUSIONS
  The list of 51 genes derived in this study might have potential for clinical utility as a prognostic gene set, and may include candidate genes of potential relevance for clinical outcome in breast cancer. According to the predictions by this expression signature, 30 of the 46 patients may have benefited from different adjuvant treatment than they received.
authors.affiliation: Department of Oncology, Institute of Clinical Sciences, Blå stråket 2, University of Gothenburg, SE-413 45, Göteborg, Sweden. elin.karlsson@oncology.gu.se
authors.forename: Elin
authors.initials: E
authors.lastname: Karlsson
authors.forename: Ulla
authors.initials: U
authors.lastname: Delle
authors.forename: Anna
authors.initials: A
authors.lastname: Danielsson
authors.forename: Björn
authors.initials: B
authors.lastname: Olsson
authors.forename: Frida
authors.initials: F
authors.lastname: Abel
authors.forename: Per
authors.initials: P
authors.lastname: Karlsson
authors.forename: Khalil
authors.initials: K
authors.lastname: Helou
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics*; D001943:Breast Neoplasms / Q000175:diagnosis* / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D018270:Carcinoma, Ductal, Breast / Q000175:diagnosis* / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D016000:Cluster Analysis; D005260:Female; D005500:Follow-Up Studies; D020869:Gene Expression Profiling; D006801:Humans; D053208:Kaplan-Meier Estimate; D008207:Lymphatic Metastasis; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D011237:Predictive Value of Tests; D011379:Prognosis
chemical_list: D014408:Biomarkers, Tumor
references.citation: BMC Genomics. 2006 Oct 30;7:278
references.pmid: 17074082
references.citation: Hum Pathol. 2004 Oct;35(10):1196-209
references.pmid: 15492986
references.citation: Mol Cell Biol. 2003 Mar;23(6):2109-22
references.pmid: 12612082
references.citation: Bioinformatics. 2005 Jan 15;21(2):171-8
references.pmid: 15308542
references.citation: Hum Genet. 2002 Oct;111(4-5):411-20
references.pmid: 12384785
references.citation: Genome Biol. 2002 Jul 15;3(8):SOFTWARE0003
references.pmid: 12186655
references.citation: Nature. 2000 Aug 17;406(6797):747-52
references.pmid: 10963602
references.citation: Breast Cancer Res. 2006;8(5):R62
references.pmid: 17069664
references.citation: Cancer Genet Cytogenet. 2007 Jan 15;172(2):139-46
references.pmid: 17213022
references.citation: Bioinformatics. 2004 Oct 12;20(15):2479-81
references.pmid: 15073010
references.citation: Carcinogenesis. 2004 Dec;25(12):2311-7
references.pmid: 15319300
references.citation: Gene. 1998 Feb 16;208(1):25-30
references.pmid: 9479038
references.citation: Breast Cancer Res Treat. 2007 Jul;103(3):319-29
references.pmid: 17123152
references.citation: N Engl J Med. 2002 Dec 19;347(25):1999-2009
references.pmid: 12490681
references.citation: EMBO J. 2006 May 3;25(9):1848-59
references.pmid: 16628223
references.citation: Cancer. 2003 Nov 15;98(10):2133-43
references.pmid: 14601082
references.citation: Clin Cancer Res. 2005 Sep 1;11(17):6400-7
references.pmid: 16144945
references.citation: Proc Natl Acad Sci U S A. 2005 Sep 20;102(38):13550-5
references.pmid: 16141321
references.citation: Oncogene. 2007 Mar 1;26(10):1507-16
references.pmid: 16936776
references.citation: Bioinformatics. 2005 Apr 1;21(7):1280-1
references.pmid: 15546938
references.citation: Oncogene. 2006 Aug 3;25(33):4534-48
references.pmid: 16547496
references.citation: World J Gastroenterol. 2006 Sep 28;12(36):5884-9
references.pmid: 17007058
references.citation: Mol Cancer Ther. 2004 Feb;3(2):161-8
references.pmid: 14985456
references.citation: Cancer Res. 2004 May 1;64(9):3037-45
references.pmid: 15126339
references.citation: Nature. 2002 Jan 31;415(6871):530-6
references.pmid: 11823860
references.citation: BMC Cancer. 2007 Apr 11;7:61
references.pmid: 17428335
references.citation: Blood. 2006 Oct 15;108(8):2726-35
references.pmid: 16763212
references.citation: Breast Cancer Res Treat. 2009 Jan;113(2):231-7
references.pmid: 18278552
references.citation: Lancet. 2005 Feb 19-25;365(9460):671-9
references.pmid: 15721472
references.citation: DNA Repair (Amst). 2002 Jul 17;1(7):517-29
references.pmid: 12509226
references.citation: Proc Natl Acad Sci U S A. 2001 Sep 11;98(19):10869-74
references.pmid: 11553815
references.citation: Nucleic Acids Res. 2007 Jan;35(Database issue):D760-5
references.pmid: 17099226
references.citation: J Cancer Res Clin Oncol. 2004 Sep;130(9):537-45
references.pmid: 15235906
references.citation: Hum Genet. 2006 Nov;120(4):581-8
references.pmid: 16972078
references.citation: Clin Cancer Res. 2006 Jul 1;12(13):3950-60
references.pmid: 16818692
references.citation: Breast Cancer. 2005;12(3):166-77
references.pmid: 16110286
references.citation: Blood. 2002 Jun 15;99(12):4540-6
references.pmid: 12036886
references.citation: CA Cancer J Clin. 2006 Mar-Apr;56(2):106-30
references.pmid: 16514137
references.citation: Lancet. 2003 May 10;361(9369):1590-6
references.pmid: 12747878
references.citation: Mol Cell. 2001 Jul;8(1):105-13
references.pmid: 11511364
references.citation: J Clin Oncol. 2006 Oct 1;24(28):4594-602
references.pmid: 17008701
references.citation: BMC Mol Biol. 2006 Jan 31;7:3
references.pmid: 16448564