title: Retrospective analysis of metastatic behaviour of breast cancer subtypes.
abstract: Among breast cancer patients who develop distant metastases, there is marked variability in the clinical course, including metastasis pattern. Here, we present a retrospective study of breast cancer patients who all developed distant metastases focusing on the association between breast cancer subtype and clinical course, including organ-specific metastasis. Tissue microarrays (TMAs) were assembled and stained for ER, PR, HER2, EGFR, CK5/6, CK14, E-Cadherin, TP53 and Ki67 for 263 breast cancer patients with metastatic disease. Tumours were classified into ER+/HER2-/Ki67high, ER+/HER2-/Ki67low, ER+/HER2+, ER-/HER2+ and ER-/HER2- groups. Relevant data related to metastasis pattern, metastasis timeline, systemic treatment and survival were retrieved. Associations between site-specific relapse and patient/tumour characteristics were assessed with multivariate models using logistic regression. Median time for development of distant metastasis was 30 months (range 0-15.3 years); 75.8 % of the distance metastases developed in the first 5 years after treatment of the primary tumour. Patients with ER-/HER2- tumours had a median overall survival of 27 months; those with HER2+ tumours of 52 months; those with ER+/HER2-/Ki67high of 76 months and those with ER+/HER2-/Ki67low of 79 months. Bone was the most common site for distant metastasis (70.6 %) followed by liver (54.5 %) and lung (31.4 %), respectively. Visceral metastasis was found in 76.8 % of the patients. Patients with ER-/HER2- tumours developed visceral metastases in 81 % and bone metastases in 55.2 %; those with HER2+ tumours developed visceral metastases in 77.4 % and bone metastases in 69.8 %; those with ER+/HER2-/Ki67high developed visceral metastases in 75.7 % and bone metastases in 87.8 % and those with ER+/HER2-/Ki67low developed visceral metastases in 76.9 % and bone metastases in 73.1 %. In metastatic breast cancer patients, tumour subtypes are associated with survival and pattern of distant metastases. These associations are of help in choices for surveillance and therapy in individual patients.
authors.affiliation: Department of Pathology, Academic Medical Center, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands, c.d.savciheijink@amc.uva.nl.
authors.forename: C Dilara
authors.initials: CD
authors.lastname: Savci-Heijink
authors.forename: Hans
authors.initials: H
authors.lastname: Halfwerk
authors.forename: Gerrit K J
authors.initials: GK
authors.lastname: Hooijer
authors.forename: Hugo M
authors.initials: HM
authors.lastname: Horlings
authors.forename: Jelle
authors.initials: J
authors.lastname: Wesseling
authors.forename: Marc J
authors.initials: MJ
authors.lastname: van de Vijver
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism*; D001943:Breast Neoplasms / Q000145:classification* / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D005260:Female; D006801:Humans; D008875:Middle Aged; D009362:Neoplasm Metastasis; D012189:Retrospective Studies; D016019:Survival Analysis; D046888:Tissue Array Analysis
chemical_list: D014408:Biomarkers, Tumor
references.citation: Nat New Biol. 1973 Apr 4;242(118):148-9
references.pmid: 4512654
references.citation: Cancer Invest. 2011 Nov;29(9):635-43
references.pmid: 22011286
references.citation: Cancer Cell. 2009 Jul 7;16(1):67-78
references.pmid: 19573813
references.citation: Ann Oncol. 2011 Aug;22(8):1736-47
references.pmid: 21709140
references.citation: Breast Cancer Res Treat. 2009 May;115(2):423-8
references.pmid: 18543098
references.citation: Eur J Cancer Clin Oncol. 1989 Feb;25(2):319-29
references.pmid: 2702986
references.citation: Nat Rev Cancer. 2002 Aug;2(8):563-72
references.pmid: 12154349
references.citation: Cancer. 2006 Aug 15;107(4):696-704
references.pmid: 16826579
references.citation: J Clin Invest. 2011 Jul;121(7):2750-67
references.pmid: 21633166
references.citation: N Engl J Med. 2004 Dec 30;351(27):2817-26
references.pmid: 15591335
references.citation: Breast Cancer Res Treat. 1991 Mar;18(1):27-32
references.pmid: 1854977
references.citation: Int J Cancer. 1991 Apr 1;47(6):922-8
references.pmid: 2010235
references.citation: N Engl J Med. 2008 Dec 25;359(26):2814-23
references.pmid: 19109576
references.citation: Histopathology. 2002 Sep;41(3A):151-2, discussion 152-3
references.pmid: 12405945
references.citation: Cancer. 2007 Dec 15;110(12):2640-7
references.pmid: 17960791
references.citation: Hum Pathol. 2006 Sep;37(9):1217-26
references.pmid: 16938528
references.citation: Tumori. 2010 May-Jun;96(3):424-32
references.pmid: 20845803
references.citation: Int J Cancer. 2011 Jun 1;128(11):2527-35
references.pmid: 21365651
references.citation: Breast Cancer Res. 2007;9(5):R65
references.pmid: 17910759
references.citation: J Cancer Res Clin Oncol. 2013 Apr;139(4):645-52
references.pmid: 23283528
references.citation: BMC Cancer. 2009 Sep 24;9:342
references.pmid: 19778431
references.citation: Cancer. 2007 Sep 1;110(5):973-9
references.pmid: 17647245
references.citation: Cell. 1991 Jul 12;66(1):107-19
references.pmid: 2070412
references.citation: Cancer. 2007 May 1;109(9):1721-8
references.pmid: 17387718
references.citation: J Cell Biol. 1991 Apr;113(1):173-85
references.pmid: 2007622
references.citation: Am J Clin Pathol. 1996 Apr;105(4):394-402
references.pmid: 8604681
references.citation: Am J Surg Pathol. 2006 Sep;30(9):1097-104
references.pmid: 16931954
references.citation: Nature. 2010 Apr 15;464(7291):999-1005
references.pmid: 20393555
references.citation: Oncogene. 1995 Oct 5;11(7):1319-26
references.pmid: 7478552
references.citation: Nature. 2000 Aug 17;406(6797):747-52
references.pmid: 10963602
references.citation: Br J Cancer. 1991 Mar;63(3):447-50
references.pmid: 1672256
references.citation: Int J Oncol. 1994 Jan;4(1):37-42
references.pmid: 21566886
references.citation: Mod Pathol. 2011 Feb;24(2):157-67
references.pmid: 21076464
references.citation: J Natl Cancer Inst. 2009 May 20;101(10):736-50
references.pmid: 19436038
references.citation: Cancer. 2004 Jan 1;100(1):44-52
references.pmid: 14692023
references.citation: Breast Cancer Res. 2011 Mar 02;13(2):R22
references.pmid: 21366896
references.citation: Clin Cancer Res. 2004 Aug 15;10(16):5367-74
references.pmid: 15328174
references.citation: Br J Cancer. 2012 Jan 17;106(2):397-404
references.pmid: 22187033
references.citation: Cancer Metastasis Rev. 1989 Aug;8(2):98-101
references.pmid: 2673568
references.citation: Br J Cancer. 1981 Sep;44(3):456-9
references.pmid: 7284240
references.citation: J Clin Oncol. 2006 Dec 20;24(36):5652-7
references.pmid: 17116942
references.citation: Breast Cancer Res Treat. 2012 Apr;132(2):523-35
references.pmid: 21671017
references.citation: Ned Tijdschr Geneeskd. 2009;153:A948
references.pmid: 20051182
references.citation: Breast Cancer Res Treat. 2013 Oct;141(3):507-14
references.pmid: 24104881
references.citation: Ann Oncol. 2008 Dec;19(12):2012-9
references.pmid: 18641006
references.citation: Clin Cancer Res. 2007 Aug 1;13(15 Pt 1):4429-34
references.pmid: 17671126
references.citation: J Cell Biol. 1991 Jul;114(2):319-27
references.pmid: 1649199
references.citation: Lancet. 2005 Feb 19-25;365(9460):671-9
references.pmid: 15721472
references.citation: J Mammary Gland Biol Neoplasia. 2007 Sep;12(2-3):153-62
references.pmid: 17566854
references.citation: J Clin Oncol. 2010 Jul 10;28(20):3271-7
references.pmid: 20498394
references.citation: Br J Cancer. 2001 Dec 14;85(12):1958-63
references.pmid: 11747340
references.citation: Semin Cancer Biol. 2012 Jun;22(3):226-33
references.pmid: 22504658
references.citation: Ann Oncol. 2004 Nov;15(11):1640-4
references.pmid: 15520065
references.citation: Eur J Cancer. 2009 Nov;45(16):2792-8
references.pmid: 19643597
references.citation: Breast Cancer Res Treat. 2003 Mar;78(1):105-18
references.pmid: 12611463
references.citation: Cancer. 2008 Nov 15;113(10):2638-45
references.pmid: 18833576
references.citation: Ann Oncol. 2012 Apr;23(4):1044-52
references.pmid: 22373539
references.citation: Hum Pathol. 2012 Mar;43(3):398-404
references.pmid: 21840040
references.citation: J Pathol. 1994 Oct;174(2):101-9
references.pmid: 7965405
references.citation: Nature. 2009 Jun 18;459(7249):1005-9
references.pmid: 19421193
references.citation: Arch Pathol Lab Med. 2007;131(1):18-43
references.pmid: 19548375
references.citation: Cancer Res. 2004 Feb 1;64(3):830-5
references.pmid: 14871808
references.citation: Lab Invest. 1995 May;72(5):506-12
references.pmid: 7745946
references.citation: N Engl J Med. 2002 Dec 19;347(25):1999-2009
references.pmid: 12490681
references.citation: J Mammary Gland Biol Neoplasia. 2001 Oct;6(4):407-17
references.pmid: 12013530
references.citation: J Clin Oncol. 2008 Oct 20;26(30):4891-8
references.pmid: 18725649
references.citation: Cancer Res. 1993 Apr 1;53(7):1696-701
references.pmid: 8453644
references.citation: Breast Cancer Res Treat. 2000 Feb;59(3):271-8
references.pmid: 10832597
references.citation: Breast Cancer Res Treat. 1985;6(2):123-30
references.pmid: 4052639
references.citation: Cancer Res. 2008 Aug 1;68(15):6092-9
references.pmid: 18676831