title: Histological types of breast cancer: how special are they?
abstract: Breast cancer is a heterogeneous disease, comprising multiple entities associated with distinctive histological and biological features, clinical presentations and behaviours and responses to therapy. Microarray-based technologies have unravelled the molecular underpinning of several characteristics of breast cancer, including metastatic propensity and histological grade, and have led to the identification of prognostic and predictive gene expression signatures. Furthermore, a molecular taxonomy of breast cancer based on transcriptomic analysis has been proposed. However, microarray studies have primarily focused on invasive ductal carcinomas of no special type. Owing to the relative rarity of special types of breast cancer, information about the biology and clinical behaviour of breast cancers conveyed by histological type has not been taken into account. Histological special types of breast cancer account for up to 25% of all invasive breast cancers. Recent studies have provided direct evidence of the existence of genotypic-phenotypic correlations. For instance, secretory carcinomas of the breast consistently harbour the t(12;15) translocation that leads to the formation of the ETV6-NTRK3 fusion gene, adenoid cystic carcinomas consistently display the t(6;9) MYB-NFIB translocation and lobular carcinomas consistently show inactivation of the CDH1 gene through multiple molecular mechanisms. Furthermore, histopathological and molecular analysis of tumours from conditional mouse models has provided direct evidence for the causative role of specific genes in the genesis of specific histological special types of breast cancer. Here we review the associations between the molecular taxonomy of breast cancer and histological special types, discuss the possible origins of the heterogeneity of breast cancer and propose an approach for the identification of novel therapeutic targets based on the study of histological special types of breast cancer.
authors.affiliation: Cancer Research UK, London Research Institute, Lincoln's Inn Fields Laboratories, London WC2A 3PX, UK.
authors.forename: Britta
authors.initials: B
authors.lastname: Weigelt
authors.forename: Felipe C
authors.initials: FC
authors.lastname: Geyer
authors.forename: Jorge S
authors.initials: JS
authors.lastname: Reis-Filho
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor / Q000378:metabolism; D001943:Breast Neoplasms / Q000145:classification* / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D005838:Genotype; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis; D010641:Phenotype
chemical_list: D014408:Biomarkers, Tumor
references.citation: Nat Med. 2009 Aug;15(8):842-4
references.pmid: 19661985
references.citation: Clin Cancer Res. 2005 Aug 15;11(16):5678-85
references.pmid: 16115903
references.citation: Cancer Cell. 2006 Nov;10(5):437-49
references.pmid: 17097565
references.citation: Oncogene. 2005 Jul 7;24(29):4660-71
references.pmid: 15897907
references.citation: Mod Pathol. 2009 Nov;22(11):1401-14
references.pmid: 19633645
references.citation: Mod Pathol. 2005 Dec;18(12):1623-31
references.pmid: 16258515
references.citation: J Pathol. 2004 Oct;204(2):131-9
references.pmid: 15376261
references.citation: Int J Cancer. 2003 Aug 20;106(2):208-15
references.pmid: 12800196
references.citation: J Pathol. 2006 Mar;208(4):495-506
references.pmid: 16429394
references.citation: Histopathology. 2008 Jun;52(7):840-6
references.pmid: 18462362
references.citation: J Natl Cancer Inst. 2006 Feb 15;98(4):262-72
references.pmid: 16478745
references.citation: J Natl Cancer Inst. 2007 Nov 21;99(22):1683-94
references.pmid: 18000219
references.citation: Oncogene. 2007 Dec 13;26(57):7859-71
references.pmid: 17603561
references.citation: Nature. 2009 Dec 24;462(7276):1005-10
references.pmid: 20033038
references.citation: J Pathol. 2008 Aug;215(4):398-410
references.pmid: 18484683
references.citation: Clin Cancer Res. 2006 Nov 15;12(22):6652-62
references.pmid: 17121884
references.citation: Am J Surg Pathol. 2005 Mar;29(3):347-53
references.pmid: 15725803
references.citation: Carcinogenesis. 2005 Apr;26(4):703-11
references.pmid: 15459022
references.citation: J Clin Pathol. 2009 Jul;62(7):604-12
references.pmid: 19561229
references.citation: Proc Natl Acad Sci U S A. 2003 Sep 2;100(18):10393-8
references.pmid: 12917485
references.citation: Mol Biol Cell. 2004 Jun;15(6):2523-36
references.pmid: 15034139
references.citation: Proc Natl Acad Sci U S A. 2003 Jul 8;100(14):8418-23
references.pmid: 12829800
references.citation: Biochim Biophys Acta. 2009 Dec;1796(2):201-15
references.pmid: 19406209
references.citation: Biochim Biophys Acta. 2010 Jan;1805(1):105-17
references.pmid: 19931353
references.citation: Mod Pathol. 2006 Feb;19(2):264-71
references.pmid: 16341146
references.citation: Cancer Res. 2006 Nov 1;66(21):10292-301
references.pmid: 17079448
references.citation: Cancer Res. 2007 Dec 15;67(24):11565-75
references.pmid: 18089785
references.citation: J Pathol. 2006 Aug;209(4):445-53
references.pmid: 16739104
references.citation: J Clin Oncol. 2008 Aug 1;26(22):3785-90
references.pmid: 18591545
references.citation: Cancer Res. 2006 May 1;66(9):4636-44
references.pmid: 16651414
references.citation: Breast Cancer Res. 2007;9(2):R23
references.pmid: 17397528
references.citation: Trends Endocrinol Metab. 2004 Jul;15(5):193-7
references.pmid: 15223047
references.citation: Nat Rev Clin Oncol. 2009 Dec;6(12):718-30
references.pmid: 19942925
references.citation: Nature. 2002 Jan 31;415(6871):530-6
references.pmid: 11823860
references.citation: Histopathology. 2008 Jan;52(1):108-18
references.pmid: 18171422
references.citation: Br J Cancer. 1997;76(9):1131-3
references.pmid: 9365159
references.citation: Ann Oncol. 2009 Nov;20(11):1763-70
references.pmid: 19602565
references.citation: J Clin Pathol. 2005 Jul;58(7):700-4
references.pmid: 15976335
references.citation: Cancer Res. 2003 Nov 1;63(21):7167-75
references.pmid: 14612510
references.citation: Ann Oncol. 2006 Apr;17(4):605-13
references.pmid: 16469754
references.citation: Proc Natl Acad Sci U S A. 2003 Apr 1;100(7):3983-8
references.pmid: 12629218
references.citation: Nat Rev Cancer. 2007 Oct;7(10):791-9
references.pmid: 17851544
references.citation: Hum Pathol. 1986 Mar;17(3):212-5
references.pmid: 2419235
references.citation: Nature. 2005 Apr 14;434(7035):917-21
references.pmid: 15829967
references.citation: Hum Pathol. 2002 Jun;33(6):628-31
references.pmid: 12152162
references.citation: Histopathology. 1992 Jun;20(6):479-89
references.pmid: 1607149
references.citation: Oncogene. 2006 Sep 25;25(43):5846-53
references.pmid: 16998499
references.citation: Nat Rev Cancer. 2007 Sep;7(9):659-72
references.pmid: 17721431
references.citation: J Pathol. 2009 Jul;218(3):301-15
references.pmid: 19479727
references.citation: J Natl Cancer Inst. 1975 Aug;55(2):231-73
references.pmid: 169369
references.citation: Histopathology. 2008 Jan;52(1):58-66
references.pmid: 18171417
references.citation: Histopathology. 1995 Sep;27(3):219-26
references.pmid: 8522285
references.citation: J Pathol. 2010 Jan;220(2):307-15
references.pmid: 19921711
references.citation: J Pathol. 2005 Nov;207(3):260-8
references.pmid: 16167361
references.citation: Genes Chromosomes Cancer. 2004 Jun;40(2):152-7
references.pmid: 15101049
references.citation: Histopathology. 2006 Jul;49(1):22-34
references.pmid: 16842243
references.citation: Nature. 2000 Aug 17;406(6797):747-52
references.pmid: 10963602
references.citation: Cancer Res. 2009 Jan 15;69(2):663-71
references.pmid: 19147582
references.citation: Proc Natl Acad Sci U S A. 2007 Jul 17;104(29):12111-6
references.pmid: 17626182
references.citation: J Clin Invest. 2007 Nov;117(11):3155-63
references.pmid: 17975657
references.citation: Lancet Oncol. 2009 Nov;10(11):1070-6
references.pmid: 19801202
references.citation: Clin Cancer Res. 2005 Jul 15;11(14):5175-80
references.pmid: 16033833
references.citation: J Pathol. 2004 Jun;203(2):661-71
references.pmid: 15141381
references.citation: Cancer Res. 2000 Feb 15;60(4):1077-83
references.pmid: 10706127
references.citation: Oncogene. 2008 Sep 11;27(40):5359-72
references.pmid: 18490921
references.citation: Clin Cancer Res. 2004 Aug 15;10(16):5367-74
references.pmid: 15328174
references.citation: Clin Cancer Res. 2008 Jul 1;14(13):4038-44
references.pmid: 18593979
references.citation: J Natl Cancer Inst. 1998 Aug 5;90(15):1138-45
references.pmid: 9701363
references.citation: Nat Med. 2009 Aug;15(8):907-13
references.pmid: 19648928
references.citation: Genes Chromosomes Cancer. 2005 Sep;44(1):103-8
references.pmid: 15887243
references.citation: Clin Cancer Res. 2007 Jan 1;13(1):90-101
references.pmid: 17200343
references.citation: Cancer Cell. 2002 Nov;2(5):367-76
references.pmid: 12450792
references.citation: Breast Cancer Res Treat. 2009 Sep;117(2):273-80
references.pmid: 18815879
references.citation: Am J Surg Pathol. 2008 Apr;32(4):513-23
references.pmid: 18223478
references.citation: J Pathol. 2008 Dec;216(4):394-8
references.pmid: 18798222
references.citation: J Pathol. 2009 Jan;217(2):229-41
references.pmid: 19009588
references.citation: Nat Rev Cancer. 2009 Feb;9(2):128-34
references.pmid: 19132008
references.citation: Cancer Res. 2001 Aug 15;61(16):5979-84
references.pmid: 11507038
references.citation: Mod Pathol. 2009 Feb;22(2):291-8
references.pmid: 19011601
references.citation: Genes Chromosomes Cancer. 1998 Dec;23(4):300-6
references.pmid: 9824202
references.citation: Am J Pathol. 2002 Dec;161(6):1991-6
references.pmid: 12466114
references.citation: Clin Cancer Res. 2009 Apr 15;15(8):2711-22
references.pmid: 19318498
references.citation: Med Hypotheses. 2001 Nov;57(5):655-66
references.pmid: 11735329
references.citation: Mol Cancer Ther. 2008 Apr;7(4):944-51
references.pmid: 18413808
references.citation: Am J Surg Pathol. 2007 Mar;31(3):417-26
references.pmid: 17325484
references.citation: Lancet. 2005 Feb 19-25;365(9460):671-9
references.pmid: 15721472
references.citation: Breast Cancer Res. 2008;10(4):R65
references.pmid: 18662380
references.citation: J Clin Oncol. 2009 Mar 10;27(8):1160-7
references.pmid: 19204204
references.citation: Major Probl Pathol. 1979;11:i-xvi, 1-466
references.pmid: 547120
references.citation: Breast Cancer Res Treat. 2008 Jul;110(2):245-56
references.pmid: 17912630
references.citation: Mol Oncol. 2010 Jun;4(3):192-208
references.pmid: 20452298
references.citation: Cancer Res. 1997 Oct 1;57(19):4360-7
references.pmid: 9331099
references.citation: Proc Natl Acad Sci U S A. 2009 Nov 3;106(44):18740-4
references.pmid: 19841262
references.citation: Oncologist. 2006 Sep;11(8):868-77
references.pmid: 16951390
references.citation: J Clin Oncol. 2008 May 20;26(15):2568-81
references.pmid: 18487574
references.citation: Nat Med. 2006 Nov;12(11):1294-300
references.pmid: 17057710
references.citation: Breast Cancer Res Treat. 2010 Feb;120(1):95-109
references.pmid: 19350388
references.citation: Breast Cancer Res Treat. 2008 Sep;111(1):121-7
references.pmid: 17929165
references.citation: J Natl Cancer Inst. 1973 May;50(5):1111-8
references.pmid: 4123242
references.citation: J Clin Oncol. 2002 May 1;20(9):2310-8
references.pmid: 11981002
references.citation: J Pathol. 2010 Jan;220(1):45-57
references.pmid: 19877120
references.citation: J Pathol. 2007 Mar;211(4):389-98
references.pmid: 17212342
references.citation: J Pathol. 2010 Apr;220(5):562-73
references.pmid: 20099298
references.citation: J Clin Pathol. 2010 Jun;63(6):492-6
references.pmid: 18552174
references.citation: J Clin Pathol. 2008 Sep;61(9):1045-50
references.pmid: 18641405
references.citation: Proc Natl Acad Sci U S A. 2001 Sep 11;98(19):10869-74
references.pmid: 11553815
references.citation: Cancer Res. 2009 May 15;69(10):4116-24
references.pmid: 19435916
references.citation: N Engl J Med. 2009 Jun 25;360(26):2719-29
references.pmid: 19516027
references.citation: Adv Anat Pathol. 2004 Nov;11(6):297-303
references.pmid: 15505530
references.citation: J Clin Oncol. 2010 Mar 1;28(7):1145-53
references.pmid: 20100965
references.citation: Mol Oncol. 2010 Jun;4(3):209-29
references.pmid: 20537966
references.citation: J Pathol. 2005 Jan;205(2):248-54
references.pmid: 15641021
references.citation: Histopathology. 1991 Nov;19(5):403-10
references.pmid: 1757079
references.citation: Breast Cancer Res. 2005;7(4):143-8
references.pmid: 15987465
references.citation: Am J Clin Pathol. 1982 Dec;78(6):806-16
references.pmid: 7148748
references.citation: Int J Cancer. 2007 Jul 1;121(1):127-35
references.pmid: 17330844
references.citation: Oncogene. 2007 Mar 29;26(14):2126-32
references.pmid: 17016441
references.citation: Breast Cancer Res. 2007;9(2):R24
references.pmid: 17417968
references.citation: Breast Cancer Res. 2009;11 Suppl 3:S12
references.pmid: 20030863
references.citation: J Natl Cancer Inst. 2003 Oct 1;95(19):1482-5
references.pmid: 14519755
references.citation: Mol Oncol. 2010 Jun;4(3):255-66
references.pmid: 20434415
references.citation: EMBO Mol Med. 2009 Sep;1(6-7):315-22
references.pmid: 20049735
references.citation: J Pathol. 2010 Jan;220(2):263-80
references.pmid: 19927298
references.citation: Cancer Res. 2010 Mar 1;70(5):2085-94
references.pmid: 20179196
references.citation: N Engl J Med. 2002 Dec 19;347(25):1999-2009
references.pmid: 12490681
references.citation: Breast Cancer Res Treat. 2010 Aug;122(3):721-31
references.pmid: 19882246
references.citation: J Pathol. 2008 Oct;216(2):141-50
references.pmid: 18720457
references.citation: N Engl J Med. 2009 Feb 19;360(8):790-800
references.pmid: 19228622
references.citation: Int J Cancer. 2001 May 1;92(3):404-8
references.pmid: 11291078
references.citation: Cancer Invest. 2008 Feb;26(1):1-10
references.pmid: 18181038
references.citation: Nature. 2009 Oct 8;461(7265):809-13
references.pmid: 19812674
references.citation: Pathobiology. 2008;75(2):119-31
references.pmid: 18544967
references.citation: Nat Rev Cancer. 2007 Apr;7(4):233-45
references.pmid: 17361217
references.citation: Histopathology. 2006 Jul;49(1):10-21
references.pmid: 16842242
references.citation: Breast Cancer Res Treat. 2007 Apr;102(2):143-55
references.pmid: 16906480
references.citation: Genes Chromosomes Cancer. 1999 Jan;24(1):72-7
references.pmid: 9892111
references.citation: Am J Surg Pathol. 2005 Jun;29(6):734-46
references.pmid: 15897740
references.citation: Genome Biol. 2007;8(5):R76
references.pmid: 17493263
references.citation: JAMA. 2006 Jun 7;295(21):2492-502
references.pmid: 16757721
references.citation: N Y State J Med. 1973 May 1;73(9):1078-82
references.pmid: 4348806
references.citation: Lancet Oncol. 2010 Apr;11(4):339-49
references.pmid: 20181526
references.citation: Int J Surg Pathol. 2009 Aug;17(4):285-302
references.pmid: 19103611
references.citation: J Pathol. 2009 Sep;219(1):131-40
references.pmid: 19562735
references.citation: Oncogene. 2006 Jun 29;25(28):3994-4008
references.pmid: 16491124
references.citation: BMC Genomics. 2006 Apr 27;7:96
references.pmid: 16643655
references.citation: J Clin Oncol. 2010 Jan 1;28(1):99-104
references.pmid: 19917872
references.citation: J Clin Oncol. 2008 Jul 1;26(19):3153-8
references.pmid: 18490649