title: The combination of Ki67, histological grade and estrogen receptor status identifies a low-risk group among 1,854 chemo-naïve women with N0/N1 primary breast cancer.
abstract: BACKGROUND
  The aim was to confirm a previously defined prognostic index, combining a proliferation marker, histological grade, and estrogen receptor (ER) in different subsets of primary N0/N1 chemo-naïve breast cancer patients.
  In the present study, including 1,854 patients, Ki67 was used in the index (KiGE), since it is the generally accepted proliferation marker in clinical routine. The low KiGE-group was defined as histological grade 1 patients and grade 2 patients which were ER-positive and had low Ki67 expression. All other patients made up the high KiGE-group. The KiGE-index separated patients into two groups with different prognosis. In multivariate analysis, KiGE was significantly associated with disease-free survival, when adjusted for age at diagnosis, tumor size and adjuvant endocrine treatment (hazard ratio: 3.5, 95% confidence interval: 2.6-4.7, P<0.0001).
  
  
  CONCLUSIONS
  We have confirmed a prognostic index based on a proliferation marker (Ki67), histological grade, and ER for identification of a low-risk group of patients with N0/N1 primary breast cancer. For this low-risk group constituting 57% of the patients, with a five-year distant disease-free survival of 92%, adjuvant chemotherapy will have limited effect and may be avoided.
authors.affiliation: Division of Oncology, Department of Clinical Sciences Lund, Skåne University Hospital, Lund University, Barngatan 2B, SE-221 85 Lund, Sweden.
authors.forename: Carina
authors.initials: C
authors.lastname: Strand
authors.forename: Martin
authors.initials: M
authors.lastname: Bak
authors.forename: Signe
authors.initials: S
authors.lastname: Borgquist
authors.forename: Gunilla
authors.initials: G
authors.lastname: Chebil
authors.forename: Anna-Karin
authors.initials: AK
authors.lastname: Falck
authors.forename: Marie-Louise
authors.initials: ML
authors.lastname: Fjällskog
authors.forename: Dorthe
authors.initials: D
authors.lastname: Grabau
authors.forename: Ingrid
authors.initials: I
authors.lastname: Hedenfalk
authors.forename: Karin
authors.initials: K
authors.lastname: Jirström
authors.forename: Marie
authors.initials: M
authors.lastname: Klintman
authors.forename: Per
authors.initials: P
authors.lastname: Malmström
authors.forename: Hans
authors.initials: H
authors.lastname: Olsson
authors.forename: Lisa
authors.initials: L
authors.lastname: Rydén
authors.forename: Olle
authors.initials: O
authors.lastname: Stål
authors.forename: Pär-Ola
authors.initials: PO
authors.lastname: Bendahl
authors.forename: Mårten
authors.initials: M
authors.lastname: Fernö
keywords: Breast cancer; Chemo-naïve; Ki67; Prognostic index; Proliferation
references.citation: BMC Cancer. 2012 Sep 11;12:403
references.pmid: 22963449
references.citation: N Engl J Med. 2004 Dec 30;351(27):2817-26
references.pmid: 15591335
references.citation: Breast Cancer Res Treat. 2012 Jul;134(1):277-82
references.pmid: 22467243
references.citation: Acta Oncol. 2003;42(7):719-25
references.pmid: 14690157
references.citation: Ann Oncol. 2011 Aug;22(8):1736-47
references.pmid: 21709140
references.citation: Ann Oncol. 2011 Sep;22 Suppl 6:vi12-24
references.pmid: 21908498
references.citation: Future Oncol. 2008 Oct;4(5):603-10
references.pmid: 18922117
references.citation: Eur J Cancer. 2005 Jan;41(2):256-64
references.pmid: 15661551
references.citation: Ann Oncol. 2009 Aug;20(8):1319-29
references.pmid: 19535820
references.citation: Clin Cancer Res. 2000 Jan;6(1):139-46
references.pmid: 10656442
references.citation: Breast Cancer Res Treat. 2011 Jun;127(3):591-9
references.pmid: 20623333
references.citation: Breast Cancer Res. 2006;8(6):216
references.pmid: 17164010
references.citation: J Natl Cancer Inst. 2006 Feb 15;98(4):262-72
references.pmid: 16478745
references.citation: Int J Cancer. 2001 Jul 15;93(2):283-7
references.pmid: 11410878
references.citation: Br J Cancer. 2002 Feb 1;86(3):402-8
references.pmid: 11875707
references.citation: J Natl Cancer Inst. 2008 Feb 6;100(3):207-12
references.pmid: 18230798
references.citation: Anticancer Res. 2006 Nov-Dec;26(6B):4415-21
references.pmid: 17201163
references.citation: Cancer Epidemiol Biomarkers Prev. 2009 Sep;18(9):2501-6
references.pmid: 19706846
references.citation: J Natl Cancer Inst. 2005 Aug 17;97(16):1180-4
references.pmid: 16106022
references.citation: Clin Cancer Res. 2008 Aug 15;14(16):5158-65
references.pmid: 18698033
references.citation: Br J Cancer. 1995 May;71(5):1029-32
references.pmid: 7734295
references.citation: Breast Cancer Res Treat. 2012 Jan;131(1):33-40
references.pmid: 21331623
references.citation: J Clin Oncol. 2007 Nov 20;25(33):5287-312
references.pmid: 17954709
references.citation: Cancer Res. 2006 Nov 1;66(21):10292-301
references.pmid: 17079448
references.citation: Lancet. 2012 Feb 4;379(9814):432-44
references.pmid: 22152853
references.citation: Breast Cancer Res Treat. 2008 Mar;108(2):259-64
references.pmid: 17530429
references.citation: J Clin Pathol. 2008 Feb;61(2):197-203
references.pmid: 18223096
references.citation: J Natl Cancer Inst. 2011 Nov 16;103(22):1656-64
references.pmid: 21960707
references.citation: J Natl Cancer Inst. 2008 Oct 1;100(19):1380-8
references.pmid: 18812550
references.citation: J Natl Cancer Inst. 1996 Nov 6;88(21):1543-9
references.pmid: 8901852
references.citation: Biometrics. 1983 Jun;39(2):499-503
references.pmid: 6354290
references.citation: Nature. 2000 Aug 17;406(6797):747-52
references.pmid: 10963602
references.citation: Breast Cancer Res Treat. 2012 Apr;132(3):895-915
references.pmid: 22048814
references.citation: J Clin Oncol. 2011 Nov 10;29(32):4273-8
references.pmid: 21990413
references.citation: Ann Oncol. 2005 Nov;16(11):1723-39
references.pmid: 15980158
references.citation: J Clin Oncol. 2005 Oct 1;23(28):7212-20
references.pmid: 16192605
references.citation: Mod Pathol. 2007 Dec;20(12):1307-15
references.pmid: 17917671
references.citation: J Clin Oncol. 2001 Feb 15;19(4):980-91
references.pmid: 11181660
references.citation: Breast Cancer Res. 2007;9(6):R81
references.pmid: 18034879
references.citation: Eur J Cancer. 2011 Dec;47(18):2742-9
references.pmid: 22051734
references.citation: Br J Cancer. 2007 May 21;96(10):1504-13
references.pmid: 17453008
references.citation: Proc Natl Acad Sci U S A. 2001 Sep 11;98(19):10869-74
references.pmid: 11553815
references.citation: J Pathol. 2003 Apr;199(4):424-31
references.pmid: 12635132
references.citation: Eur J Cancer. 2004 Aug;40(12):1837-41
references.pmid: 15288284
references.citation: Mod Pathol. 2010 Feb;23(2):251-9
references.pmid: 19935641
references.citation: Genome Biol. 2007;8(8):R157
references.pmid: 17683518
references.citation: Breast Cancer Res Treat. 2009 Jul;116(1):53-68
references.pmid: 18592370