title: Molecular subtypes, histopathological grade and survival in a historic cohort of breast cancer patients.
abstract: Molecular subtyping of breast cancer may provide additional prognostic information regarding patient outcome. However, its clinical significance remains to be established. In this study, the main aims were to discover whether reclassification of breast cancer into molecular subtypes provides more precise information regarding outcome compared to conventional histopathological grading and to study breast cancer-specific survival in the different molecular subtypes. Cases of breast cancer occurring in a cohort of women born between 1886 and 1928 with long-term follow-up were included in the study. Tissue microarrays were constructed from archival formalin-fixed, paraffin-embedded tissue from 909 cases. Using immunohistochemistry and in situ hybridisation as surrogates for gene expression analyses, all cases were reclassified into the following molecular subtypes: Luminal A; Luminal B (HER2-); Luminal B (HER2+); HER2 subtype; Basal phenotype; and five negative phenotype. Kaplan-Meier survival curves and Cox proportional hazards models were used in the analyses. During the first 5 years after diagnosis, there were significant differences in prognosis according to molecular subtypes with the best survival for the Luminal A subtype and the worst for HER2 and five negative phenotype. In this historic cohort of women with breast cancer, differences in breast cancer-specific survival according to subtype occur almost exclusively amongst the histopathological grade 2 tumours. From 5 years after time of diagnosis until the end of follow-up, there appears to be no difference in survival according to molecular subtype or histopathological grade.
authors.affiliation: Department of Laboratory Medicine, Children's and Women's Health, Norwegian University of Science and Technology, Trondheim, Norway. Monica.j.engstrom@ntnu.no
authors.forename: M J
authors.initials: MJ
authors.lastname: Engstrøm
authors.forename: S
authors.initials: S
authors.lastname: Opdahl
authors.forename: A I
authors.initials: AI
authors.lastname: Hagen
authors.forename: P R
authors.initials: PR
authors.lastname: Romundstad
authors.forename: L A
authors.initials: LA
authors.lastname: Akslen
authors.forename: O A
authors.initials: OA
authors.lastname: Haugen
authors.forename: L J
authors.initials: LJ
authors.lastname: Vatten
authors.forename: A M
authors.initials: AM
authors.lastname: Bofin
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000378:metabolism* / Q000401:mortality* / Q000473:pathology*; D015331:Cohort Studies; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D053208:Kaplan-Meier Estimate; D019394:Ki-67 Antigen / Q000378:metabolism; D008875:Middle Aged; D009664:Norway / Q000453:epidemiology; D016016:Proportional Hazards Models; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D011960:Receptors, Estrogen / Q000378:metabolism; D011980:Receptors, Progesterone / Q000378:metabolism; D046888:Tissue Array Analysis
chemical_list: D019394:Ki-67 Antigen; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; C508053:ERBB2 protein, human
references.citation: J Natl Cancer Inst. 2006 Feb 15;98(4):262-72
references.pmid: 16478745
references.citation: Breast Cancer Res. 2010;12(4):207
references.pmid: 20804570
references.citation: Hum Pathol. 1995 Aug;26(8):873-9
references.pmid: 7635449
references.citation: Nature. 2000 Aug 17;406(6797):747-52
references.pmid: 10963602
references.citation: Breast Cancer Res Treat. 2008 Feb;107(3):309-30
references.pmid: 17377838
references.citation: Ann Oncol. 2011 Aug;22(8):1736-47
references.pmid: 21709140
references.citation: Cancer. 2004 Apr 1;100(7):1331-6
references.pmid: 15042664
references.citation: Breast Cancer. 2004;11(3):267-75
references.pmid: 15550845
references.citation: J Clin Oncol. 2009 Mar 10;27(8):1323-33
references.pmid: 19204209
references.citation: Patholog Res Int. 2011;2011:890938
references.pmid: 21845210
references.citation: Ann Oncol. 2012 Dec;23(12):2997-3006
references.pmid: 23166150
references.citation: Pathobiology. 2011;78(2):99-114
references.pmid: 21677473
references.citation: Breast Cancer Res. 2013 Jan 14;15(1):101
references.pmid: 23316883
references.citation: Am J Clin Pathol. 2008 Nov;130(5):724-30
references.pmid: 18854264
references.citation: J Cancer Res Clin Oncol. 2013 Feb;139(2):181-5
references.pmid: 22961208
references.citation: Breast Cancer Res Treat. 2013 Apr;138(3):691-8
references.pmid: 23504136
references.citation: Br J Cancer. 2013 Mar 19;108(5):1042-51
references.pmid: 23462719
references.citation: J Clin Pathol. 2011 Aug;64(8):649-53
references.pmid: 21690244
references.citation: Ann Surg Oncol. 2013 Jan;20(1):87-93
references.pmid: 22875649
references.citation: Am J Epidemiol. 1987 Nov;126(5):831-41
references.pmid: 3661531
references.citation: Breast Cancer Res Treat. 2006 Nov;100(2):229-35
references.pmid: 16932852
references.citation: Arch Pathol Lab Med. 2010 Jun;134(6):907-22
references.pmid: 20524868
references.citation: PLoS Med. 2010 May 25;7(5):e1000279
references.pmid: 20520800
references.citation: Ann Oncol. 2013 Feb;24(2):283-291
references.pmid: 23022997
references.citation: Breast Cancer Res. 2012 Oct 01;14(5):R129
references.pmid: 23025714
references.citation: J Clin Pathol. 2008 Jul;61(7):818-24
references.pmid: 18381380
references.citation: J Clin Pathol. 2008 Jun;61(6):757-60
references.pmid: 18326010
references.citation: Breast Care (Basel). 2011;6(2):136-141
references.pmid: 21633630
references.citation: Br J Cancer. 2009 Oct 20;101(8):1338-44
references.pmid: 19773756
references.citation: Int J Cancer. 2010 Dec 15;127(12):2893-917
references.pmid: 21351269
references.citation: Breast Cancer Res Treat. 2013 Jan;137(2):523-31
references.pmid: 23184079
references.citation: APMIS. 2007 Dec;115(12):1391-9
references.pmid: 18184410
references.citation: Breast Cancer Res Treat. 2011 Feb;126(1):185-92
references.pmid: 20711652
references.citation: Histopathology. 1991 Nov;19(5):403-10
references.pmid: 1757079
references.citation: Breast Cancer Res Treat. 2012 Aug;135(1):291-9
references.pmid: 22833199
references.citation: Histopathology. 2010 May;56(6):702-7
references.pmid: 20546335
references.citation: Br J Cancer. 1957 Sep;11(3):359-77
references.pmid: 13499785
references.citation: BMC Cancer. 2007 Jul 24;7:134
references.pmid: 17650314
references.citation: J Natl Cancer Inst. 2003 Oct 1;95(19):1482-5
references.pmid: 14519755
references.citation: Clin Cancer Res. 2008 Mar 1;14(5):1368-76
references.pmid: 18316557
references.citation: Lancet. 2012 Nov 24;380(9856):1840-50
references.pmid: 23079588
references.citation: Ann Oncol. 2009 Aug;20(8):1319-29
references.pmid: 19535820
references.citation: Br J Cancer. 2011 Aug 23;105(5):731-6
references.pmid: 21811252