An "elite hacker": Beast tumors exploit the normal microenvironment program to instruct their progression and biological diversity

Cell Adhesion and Migration

Volumn 6, Issue 3, 2012, Pages 236-435

  Boudreau, Aaron ^a   Van't Veer, Laura J ^a   Bissell, Mina J ^b  

^a UNIVERSITY OF CALIFORNIA   (United States)

^b LAWRENCE BERKELEY NATIONAL LABORATORY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

NONSTEROID ANTIINFLAMMATORY AGENT;

BIODIVERSITY; BRANCHING MORPHOGENESIS; BREAST CANCER; BREAST TUMOR; CANCER GROWTH; CARCINOMA IN SITU; CELL DIFFERENTIATION; CELL HETEROGENEITY; EXTRACELLULAR MATRIX; FIBROBLAST; HUMAN; INVASIVE CARCINOMA; MAMMARY GLAND; MOLECULAR INTERACTION; NONHUMAN; REVIEW; SIGNAL TRANSDUCTION; STROMA CELL; TUMOR GROWTH; TUMOR MICROENVIRONMENT; ANIMAL; CELL TRANSFORMATION; FEMALE; METABOLISM; PARACRINE SIGNALING; PATHOLOGY; PATHOPHYSIOLOGY;

ANIMALS; BREAST NEOPLASMS; CELL TRANSFORMATION, NEOPLASTIC; EXTRACELLULAR MATRIX; FEMALE; HUMANS; MAMMARY GLANDS, HUMAN; PARACRINE COMMUNICATION; SIGNAL TRANSDUCTION; TUMOR MICROENVIRONMENT;

EID: 84864927191     PISSN: 19336918     EISSN: 19336926     Source Type: Journal    
DOI: 10.4161/cam.20880     Document Type: Review

References (208)

1. Daniel CW, Smith GH. The mammary gland: a model for development. J Mammary Gland Biol Neoplasia 1999; 4:3-8; PMID:10219902; http://dx.doi.org/10. 1023/A:1018796301609
2. Richert MM, Schwertfeger KL, Ryder JW, Anderson SM. An atlas of mouse mammary gland development. J Mammary Gland Biol Neoplasia 2000; 5:227-41; PMID:11149575; http://dx.doi.org/10.1023/A:1026499523505
3. Bissell MJ, Radisky D. Putting tumours in context. Nat Rev Cancer 2001; 1:46-54; PMID:11900251; http://dx.doi.org/10.1038/35094059
4. Bissell M, Polyak K, Rosen JM. The mammary gland as an experimental model: a subject collection from Cold Spring Harbor perspectives in biology. Cold Spring Harbor, N.Y.: Cold Spring Harbor Laboratory Press, 2011.
5. Rønnov-Jessen L, Petersen OW, Bissell MJ. Cellular changes involved in conversion of normal to malignant breast: importance of the stromal reaction. Physiol Rev 1996; 76:69-125; PMID:8592733
6. Maller O, Martinson H, Schedin P. Extracellular matrix composition reveals complex and dynamic stromal-epithelial interactions in the mammary gland. J Mammary Gland Biol Neoplasia 2010; 15:301-18; PMID:20811805; http://dx.doi.org/10.1007/s10911-010-9189-6
7. Lu P, Werb Z. Patterning mechanisms of branched organs. Science 2008; 322:1506-9; PMID:19056977; http://dx.doi.org/10.1126/science.1162783
8. Sternlicht MD, Kouros-Mehr H, Lu P, Werb Z. Hormonal and local control of mammary branching morphogenesis. Differentiation 2006; 74:365-81; PMID:16916375; http://dx.doi.org/10.1111/j.1432-0436.2006.00105.x
9. Sakakura T, Nishizuka Y, Dawe CJ. Mesenchyme-dependent morphogenesis and epithelium-specific cytodifferentiation in mouse mammary gland. Science 1976; 194:1439-41; PMID:827022; http://dx.doi.org/10.1126/science.827022
10. Sakakura T, Sakagami Y, Nishizuka Y. Persistence of responsiveness of adult mouse mammary gland to induction by embryonic mesenchyme. Dev Biol 1979; 72:201-10; PMID:510783; http://dx.doi.org/10.1016/0012-1606(79)90111-8
11. DeCosse JJ, Gossens CL, Kuzma JF, Unsworth BR. Breast cancer: induction of differentiation by embryonic tissue. Science 1973; 181:1057-8; PMID:4269415; http://dx.doi.org/10.1126/science.181.4104.1057
12. DeCosse JJ, Gossens C, Kuzma JF, Unsworth BR. Embryonic inductive tissues that cause histologic differentiation of murine mammary carcinoma in vitro. J Natl Cancer Inst 1975; 54:913-22; PMID:1127721
13. Booth BW, Mack DL, Androutsellis-Theotokis A, McKay RD, Boulanger CA, Smith GH. The mammary microenvironment alters the differentiation repertoire of neural stem cells. Proc Natl Acad Sci U S A 2008; 105:14891-6; PMID:18809919; http://dx.doi.org/10.1073/pnas.0803214105
14. Boulanger CA, Mack DL, Booth BW, Smith GH. Interaction with the mammary microenvironment redirects spermatogenic cell fate in vivo. Proc Natl Acad Sci U S A 2007; 104:3871-6; PMID:17360445; http://dx.doi.org/10.1073/pnas.0611637104
15. Bussard KM, Boulanger CA, Booth BW, Bruno RD, Smith GH. Reprogramming human cancer cells in the mouse mammary gland. Cancer Res 2010; 70:6336-43; PMID:20647316; http://dx.doi.org/10.1158/0008-5472.CAN-10-0591
16. Kouros-Mehr H, Werb Z. Candidate regulators of mammary branching morphogenesis identified by genome-wide transcript analysis. Dev Dyn 2006; 235:3404-12; PMID:17039550; http://dx.doi.org/10.1002/dvdy.20978
17. Pavlovich AL, Boghaert E, Nelson CM. Mammary branch initiation and extension are inhibited by separate pathways downstream of TGF&beta in culture. Exp Cell Res 2011; 317:1872-84; PMID:21459084; http://dx.doi.org/10. 1016/j.yexcr.2011.03.017
18. Vaught D, Chen J, Brantley-Sieders DM. Regulation of mammary gland branching morphogenesis by EphA2 receptor tyrosine kinase. Mol Biol Cell 2009; 20:2572-81; PMID:19321667; http://dx.doi.org/10.1091/mbc.E08-04-0378
19. Soriano JV, Pepper MS, Nakamura T, Orci L, Montesano R. Hepatocyte growth factor stimulates extensive development of branching duct-like structures by cloned mammary gland epithelial cells. J Cell Sci 1995; 108:413-30; PMID:7768990
20. Fata JE, Mori H, Ewald AJ, Zhang H, Yao E, Werb Z, et al. The MAPK(ERK-1,2) pathway integrates distinct and antagonistic signals from TGFalpha and FGF7 in morphogenesis of mouse mammary epithelium. Dev Biol 2007; 306:193-207; PMID:17448457; http://dx.doi.org/10.1016/j.ydbio.2007.03.013
21. Snedeker SM, Brown CF, DiAugustine RP. Expression and functional properties of transforming growth factor alpha and epidermal growth factor during mouse mammary gland ductal morphogenesis. Proc Natl Acad Sci U S A 1991; 88:276-80; PMID:1986376; http://dx.doi.org/10.1073/pnas.88.1.276
22. Yang Y, Spitzer E, Meyer D, Sachs M, Niemann C, Hartmann G, et al. Sequential requirement of hepatocyte growth factor and neuregulin in the morphogenesis and differentiation of the mammary gland. J Cell Biol 1995; 131:215-26; PMID:7559778; http://dx.doi.org/10.1083/jcb.131.1.215
23. Hirai Y, Lochter A, Galosy S, Koshida S, Niwa S, Bissell MJ. Epimorphin functions as a key morph-oregulator for mammary epithelial cells. J Cell Biol 1998; 140:159-69; PMID:9425164; http://dx.doi.org/10.1083/jcb.140.1.159
24. Hovey RC, Aimo L. Diverse and active roles for adipocytes during mammary gland growth and function. J Mammary Gland Biol Neoplasia 2010; 15:279-90; PMID:20717712; http://dx.doi.org/10.1007/s10911-010-9187-8
25. Gouon-Evans V, Pollard JW. Unexpected deposition of brown fat in mammary gland during postnatal development. Mol Endocrinol 2002; 16:2618-27; PMID:12403850; http://dx.doi.org/10.1210/me.2001-0337
26. Landskroner-Eiger S, Park J, Israel D, Pollard JW, Scherer PE. Morphogenesis of the developing mammary gland: stage-dependent impact of adipocytes. Dev Biol 2010; 344:968-78; PMID:20599899; http://dx.doi.org/10.1016/ j.ydbio.2010.06.019
27. Celis JE, Moreira JM, Cabezón T, Gromov P, Friis E, Rank F, et al. Identification of extracellular and intracellular signaling components of the mammary adipose tissue and its interstitial fluid in high risk breast cancer patients: toward dissecting the molecular circuitry of epithelial-adipocyte stromal cell interactions. Mol Cell Proteomics 2005; 4:492-522; PMID:15695426; http://dx.doi.org/10.1074/mcp.M500030-MCP200
28. Wang P, Mariman E, Renes J, Keijer J. The secretory function of adipocytes in the physiology of white adipose tissue. J Cell Physiol 2008; 216:3-13; PMID:18264975; http://dx.doi.org/10.1002/jcp.21386
29. Feuermann Y, Mabjeesh SJ, Shamay A. Mammary Fat Can Adjust Prolactin Effect on Mammary Epithelial Cells via Leptin and Estrogen. Int J Endocrinol 2009; 2009:427260; PMID:20049155; http://dx.doi.org/10.1155/2009/427260
30. Mueller SO, Clark JA, Myers PH, Korach KS. Mammary gland development in adult mice requires epithelial and stromal estrogen receptor alpha. Endocrinology 2002; 143:2357-65; PMID:12021201; http://dx.doi.org/10.1210/en. 143.6.2357
31. Cunha GR, Young P, Hom YK, Cooke PS, Taylor JA, Lubahn DB. Elucidation of a role for stromal steroid hormone receptors in mammary gland growth and development using tissue recombinants. J Mammary Gland Biol Neoplasia 1997; 2:393-402; PMID:10935027; http://dx.doi.org/10.1023/A:1026303630843
32. Zinger M, McFarland M, Ben-Jonathan N. Prolactin expression and secretion by human breast glandular and adipose tissue explants. J Clin Endocrinol Metab 2003; 88:689-96; PMID:12574200; http://dx.doi.org/10.1210/jc.2002-021255
33. Hovey RC, Trott JF, Ginsburg E, Goldhar A, Sasaki MM, Fountain SJ, et al. Transcriptional and spatio-temporal regulation of prolactin receptor mRNA and cooperativity with progesterone receptor function during ductal branch growth in the mammary gland. Dev Dyn 2001; 222:192-205; PMID:11668597; http://dx.doi.org/10.1002/dvdy.1179
34. Gouon-Evans V, Rothenberg ME, Pollard JW. Postnatal mammary gland development requires macrophages and eosinophils. Development 2000; 127:2269-82; PMID:10804170
35. Gouon-Evans V, Lin EY, Pollard JW. Requirement of macrophages and eosinophils and their cytokines/chemokines for mammary gland development. Breast Cancer Res 2002; 4:155-64; PMID:12100741; http://dx.doi.org/10.1186/bcr441
36. Ingman WV, Wyckoff J, Gouon-Evans V, Condeelis J, Pollard JW. Macrophages promote collagen fibrillo-genesis around terminal end buds of the developing mammary gland. Dev Dyn 2006; 235:3222-9; PMID: 17029292; http://dx.doi.org/10. 1002/dvdy.20972
37. Lilla JN, Werb Z. Mast cells contribute to the stromal microenvironment in mammary gland branching morphogenesis. Dev Biol 2010; 337:124-33; PMID:19850030; http://dx.doi.org/10.1016/j.ydbio.2009.10.021
38. Arendt LM, Rudnick JA, Keller PJ, Kuperwasser C. Stroma in breast development and disease. Semin Cell Dev Biol 2010; 21:11-8; PMID:19857593; http://dx.doi.org/10.1016/j.semcdb.2009.10.003
39. Simian M, Hirai Y, Navre M, Werb Z, Lochter A, Bissell MJ. The interplay of matrix metalloproteinases, morphogens and growth factors is necessary for branching of mammary epithelial cells. Development 2001; 128:3117-31; PMID:11688561
40. Soriano JV, Pepper MS, Orci L, Montesano R. Roles of hepatocyte growth factor/scatter factor and transforming growth factor-beta1 in mammary gland ductal morphogenesis. J Mammary Gland Biol Neoplasia 1998; 3:133-50; PMID:10819523; http://dx.doi.org/10.1023/A:1018790705727
41. Niranjan B, Buluwela L, Yant J, Perusinghe N, Atherton A, Phippard D, et al. HGF/SF: a potent cytokine for mammary growth, morphogenesis and development. Development 1995; 121:2897-908; PMID:7555716
42. Montesano R, Matsumoto K, Nakamura T, Orci L. Identification of a fibroblast-derived epithelial morphogen as hepatocyte growth factor. Cell 1991; 67:901-8; PMID:1835669; http://dx.doi.org/10.1016/0092-8674(91)90363-4
43. Garner OB, Bush KT, Nigam KB, Yamaguchi Y, Xu D, Esko JD, et al. Stage-dependent regulation of mammary ductal branching by heparan sulfate and HGF-cMet signaling. Dev Biol 2011; 355:394-403; PMID:21586278; http://dx.doi.org/10.1016/j.ydbio.2011.04.035
44. Niemann C, Brinkmann V, Spitzer E, Hartmann G, Sachs M, Naundorf H, et al. Reconstitution of mammary gland development in vitro: requirement of c-met and c-erbB2 signaling for branching and alveolar morphogenesis. J Cell Biol 1998; 143:533-45; PMID:9786961; http://dx.doi.org/10.1083/jcb.143.2.533
45. Lin C, Buxton MB, Moore D, Krontiras H, Carey L, Demichele A, et al. I-SPY TRIAL Investigators. Locally advanced breast cancers are more likely to present as Interval Cancers: results from the I-SPY 1 TRIAL (CALGB 150007/150012, ACRIN 6657, InterSPORE Trial). Breast Cancer Res Treat 2011; 132:871-9; PMID:21796368; http://dx.doi.org/10.1007/s10549-011-1670-4
46. Deome KB, Faulkin LJ, Jr., Bern HA, Blair PB. Development of mammary tumors from hyperplastic alveolar nodules transplanted into gland-free mammary fat pads of female C3H mice. Cancer Res 1959; 19:515-20; PMID:13663040
47. Mailleux AA, Spencer-Dene B, Dillon C, Ndiaye D, Savona-Baron C, Itoh N, et al. Role of FGF10/FGFR2b signaling during mammary gland development in the mouse embryo. Development 2002; 129:53-60; PMID:11782400
48. Esserman LJ, Berry DA, Cheang MC, Yau C, Perou CM, Carey L, et al. The I-SPY 1 TRIAL Investigators. Chemotherapy response and recurrence-free survival in neoadjuvant breast cancer depends on biomarker profiles: results from the I-SPY 1 TRIAL (CALGB 150007/150012; ACRIN 6657). Breast Cancer Res Treat 2012; 132:1049-62; PMID:22198468; http://dx.doi.org/10.1007/s10549-011-1895-2
49. Esserman LJ, Woodcock J. Accelerating identification and regulatory approval of investigational cancer drugs. JAMA 2011; 306:2608-9; PMID:22187281; http://dx.doi.org/10.1001/jama.2011.1837
50. Andersen K, Mori H, Fata J, Bascom J, Oyjord T, Mælandsmo GM, et al. The metastasis-promoting protein S100A4 regulates mammary branching morphogenesis. Dev Biol 2011; 352:181-90; PMID:21195708; http://dx.doi.org/10. 1016/j.ydbio.2010.12.033
51. Aboussekhra A. Role of cancer-associated fibroblasts in breast cancer development and prognosis. Int J Dev Biol 2011; 55:841-9; PMID:22161840; http://dx.doi.org/10.1387/ijdb.113362aa
52. Esserman LJ, Shieh Y, Rutgers EJ, Knauer M, Retèl VP, Mook S, et al. Impact of mammographic screening on the detection of good and poor prognosis breast cancers. Breast Cancer Res Treat 2011; 130:725-34; PMID:21892702; http://dx.doi.org/10.1007/s10549-011-1748-z
53. Engler AJ, Sen S, Sweeney HL, Discher DE. Matrix elasticity directs stem cell lineage specification. Cell 2006; 126:677-89; PMID:16923388; http://dx.doi.org/10.1016/j.cell.2006.06.044
54. Paszek MJ, Zahir N, Johnson KR, Lakins JN, Rozenberg GI, Gefen A, et al. Tensional homeostasis and the malignant phenotype. Cancer Cell 2005; 8:241-54; PMID:16169468; http://dx.doi.org/10.1016/j.ccr.2005.08.010
55. Ricard-Blum S. The collagen family. Cold Spring Harb Perspect Biol 2011; 3:a004978; PMID:21421911; http://dx.doi.org/10.1101/cshperspect.a004978
56. Wiseman BS, Sternlicht MD, Lund LR, Alexander CM, Mott J, Bissell MJ, et al. Site-specific inductive and inhibitory activities of MMP-2 and MMP-3 orchestrate mammary gland branching morphogenesis. J Cell Biol 2003; 162:1123-33; PMID:12975354; http://dx.doi.org/10.1083/jcb.200302090
57. Lee PP, Hwang JJ, Murphy G, Ip MM. Functional significance of MMP-9 in tumor necrosis factor-induced proliferation and branching morphogenesis of mammary epithelial cells. Endocrinology 2000; 141:3764-73; PMID:11014232; http://dx.doi.org/10.1210/en.141.10.3764
58. Rudolph-Owen LA, Cannon P, Matrisian LM. Overexpression of the matrix metalloproteinase matrilysin results in premature mammary gland differentiation and male infertility. Mol Biol Cell 1998; 9:421-35; PMID:9450965
59. Sympson CJ, Talhouk RS, Alexander CM, Chin JR, Clift SM, Bissell MJ, et al. Targeted expression of stromelysin-1 in mammary gland provides evidence for a role of proteinases in branching morphogenesis and the requirement for an intact basement membrane for tissue-specific gene expression. J Cell Biol 1994; 125:681-93; PMID:8175886; http://dx.doi.org/10.1083/jcb.125.3.681
60. Khokha R, Werb Z. Mammary gland reprogramming: metalloproteinases couple form with function. Cold Spring Harb Perspect Biol 2011; 3:a004333; PMID:21106646; http://dx.doi.org/10.1101/cshperspect.a004333
61. Levental KR, Yu H, Kass L, Lakins JN, Egeblad M, Erler JT, et al. Matrix crosslinking forces tumor progression by enhancing integrin signaling. Cell 2009; 139:891-906; PMID:19931152; http://dx.doi.org/10.1016/j.cell.2009.10.027
62. Itakura K, Lessing J, Sakata T, Heinzerling A, Vriens E, Wisner D, et al. The impact of preoperative magnetic resonance imaging on surgical treatment and outcomes for ductal carcinoma in situ. Clin Breast Cancer 2011; 11:33-8; PMID:21421520
63. Gudjonsson T, Rønnov-Jessen L, Villadsen R, Rank F, Bissell MJ, Petersen OW. Normal and tumor-derived myoepithelial cells differ in their ability to interact with luminal breast epithelial cells for polarity and basement membrane deposition. J Cell Sci 2002; 115:39-50; PMID:11801722
64. Chiquet-Ehrismann R, Kalla P, Pearson CA, Beck K, Chiquet M. Tenascin interferes with fibronectin action. Cell 1988; 53:383-90; PMID:2452695; http://dx.doi.org/10.1016/0092-8674(88)90158-4
65. Jones PL, Boudreau N, Myers CA, Erickson HP, Bissell MJ. Tenascin-C inhibits extracellular matrix-dependent gene expression in mammary epithelial cells. Localization of active regions using recombinant tenascin fragments. J Cell Sci 1995; 108:519-27; PMID:7539436
66. Muschler J, Streuli CH. Cell-matrix interactions in mammary gland development and breast cancer. Cold Spring Harb Perspect Biol 2010; 2:a003202; PMID:20702598; http://dx.doi.org/10.1101/cshperspect.a003202
67. Xu R, Boudreau A, Bissell MJ. Tissue architecture and function: dynamic reciprocity via extra- and intracellular matrices. Cancer Metastasis Rev 2009; 28:167-76; PMID:19160017; http://dx.doi.org/10.1007/s10555-008-9178-z
68. Liotta LA, Wicha MS, Foidart JM, Rennard SI, Garbisa S, Kidwell WR. Hormonal requirements for basement membrane collagen deposition by cultured rat mammary epithelium. Lab Invest 1979; 41:511-8; PMID:390239
69. Petersen OW, Rønnov-Jessen L, Howlett AR, Bissell MJ. Interaction with basement membrane serves to rapidly distinguish growth and differentiation pattern of normal and malignant human breast epithelial cells. Proc Natl Acad Sci U S A 1992; 89:9064-8; PMID: 1384042; http://dx.doi.org/10.1073/pnas.89.19. 9064
70. Chen J, Diacovo TG, Grenache DG, Santoro SA, Zutter MM. The alpha(2) integrin subunit-deficient mouse: a multifaceted phenotype including defects of branching morphogenesis and hemostasis. Am J Pathol 2002; 161:337-44; PMID:12107118; http://dx.doi.org/10.1016/S0002-9440(10)64185-5
71. Taddei I, Deugnier MA, Faraldo MM, Petit V, Bouvard D, Medina D, et al. Beta1 integrin deletion from the basal compartment of the mammary epithelium affects stem cells. Nat Cell Biol 2008; 10:716-22; PMID:18469806; http://dx.doi.org/10.1038/ncb1734
72. Keely PJ, Wu JE, Santoro SA. The spatial and temporal expression of the alpha 2 beta 1 integrin and its ligands, collagen I, collagen IV, and laminin, suggest important roles in mouse mammary morphogenesis. Differentiation 1995; 59:1-13; PMID:7589890; http://dx.doi.org/10.1046/j.1432-0436.1995.5910001.x
73. Naylor MJ, Li N, Cheung J, Lowe ET, Lambert E, Marlow R, et al. Ablation of beta1 integrin in mammary epithelium reveals a key role for integrin in glandular morphogenesis and differentiation. J Cell Biol 2005; 171:717-28; PMID:16301336; http://dx.doi.org/10.1083/jcb.200503144
74. Wicha MS, Liotta LA, Vonderhaar BK, Kidwell WR. Effects of inhibition of basement membrane collagen deposition on rat mammary gland development. Dev Biol 1980; 80:253-6; PMID:7450284; http://dx.doi.org/10.1016/0012-1606(80)90402-9
75. Barcellos-Hoff MH, Aggeler J, Ram TG, Bissell MJ. Functional differentiation and alveolar morphogenesis of primary mammary cultures on reconstituted basement membrane. Development 1989; 105:223-35; PMID:2806122
76. Weaver VM, Petersen OW, Wang F, Larabell CA, Briand P, Damsky C, et al. Reversion of the malignant phenotype of human breast cells in three-dimensional culture and in vivo by integrin blocking antibodies. J Cell Biol 1997; 137:231-45; PMID:9105051; http://dx.doi.org/10.1083/jcb.137.1.231
77. Debnath J, Muthuswamy SK, Brugge JS. Morphogenesis and oncogenesis of MCF-10A mammary epithelial acini grown in three-dimensional basement membrane cultures. Methods 2003; 30:256-68; PMID:12798140; http://dx.doi.org/10.1016/ S1046-2023(03)00032-X
78. Li ML, Aggeler J, Farson DA, Hatier C, Hassell J, Bissell MJ. Influence of a reconstituted basement membrane and its components on casein gene expression and secretion in mouse mammary epithelial cells. Proc Natl Acad Sci U S A 1987; 84:136-40; PMID:3467345; http://dx.doi.org/10.1073/pnas.84.1.136
79. Streuli CH, Bailey N, Bissell MJ. Control of mammary epithelial differentiation: basement membrane induces tissue-specific gene expression in the absence of cell-cell interaction and morphological polarity. J Cell Biol 1991; 115:1383-95; PMID:1955479; http://dx.doi.org/10.1083/jcb.115.5.1383
80. Allinen M, Beroukhim R, Cai L, Brennan C, Lahti-Domenici J, Huang H, et al. Molecular characterization of the tumor microenvironment in breast cancer. Cancer Cell 2004; 6:17-32; PMID:15261139; http://dx.doi.org/10.1016/j.ccr.2004. 06.010
81. Lim E, Vaillant F, Wu D, Forrest NC, Pal B, Hart AH, et al. kConFab. Aberrant luminal progenitors as the candidate target population for basal tumor development in BRCA1 mutation carriers. Nat Med 2009; 15:907-13; PMID:19648928; http://dx.doi.org/10.1038/nm.2000
82. Molyneux G, Geyer FC, Magnay FA, McCarthy A, Kendrick H, Natrajan R, et al. BRCA1 basal-like breast cancers originate from luminal epithelial progenitors and not from basal stem cells. Cell Stem Cell 2010; 7:403-17; PMID:20804975; http://dx.doi.org/10.1016/j.stem.2010.07.010
83. Ma XJ, Dahiya S, Richardson E, Erlander M, Sgroi DC. Gene expression profiling of the tumor microenvironment during breast cancer progression. Breast Cancer Res 2009; 11:R7; PMID:19187537; http://dx.doi.org/10.1186/bcr2222
84. Bissell MJ, Hines WC. Why don't we get more cancer? A proposed role of the microenvironment in restraining cancer progression. Nat Med 2011; 17:320-9; PMID:21383745; http://dx.doi.org/10.1038/nm.2328
85. Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell 2011; 144:646-74; PMID: 21376230; http://dx.doi.org/10.1016/j.cell.2011.02.013
86. Polyak K, Kalluri R. The role of themicroenvironment in mammary gland development and cancer. Cold Spring Harb Perspect Biol 2010; 2:a003244; PMID:20591988; http://dx.doi.org/10.1101/cshperspect.a003244
87. Liu S, Ginestier C, Ou SJ, Clouthier SG, Patel SH, Monville F, et al. Breast cancer stem cells are regulated by mesenchymal stem cells through cytokine networks. Cancer Res 2011; 71:614-24; PMID:21224357; http://dx.doi.org/10.1158/0008-5472.CAN-10-0538
88. Pavlakis K, Messini I, Vrekoussis T, Yiannou P, Keramopoullos D, Louvrou N, et al. The assessment of angiogenesis and fibroblastic stromagenesis in hyperplastic and pre-invasive breast lesions. BMC Cancer 2008; 8:88; PMID:18384688; http://dx.doi.org/10.1186/1471-2407-8-88
89. Sharma M, Beck AH, Webster JA, Espinosa I, Montgomery K, Varma S, et al. Analysis of stromal signatures in the tumor microenvironment of ductal carcinoma in situ. Breast Cancer Res Treat 2010; 123:397-404; PMID:19949854; http://dx.doi.org/10.1007/s10549-009-0654-0
90. Rattigan Y, Hsu JM, Mishra PJ, Glod J, Banerjee D. Interleukin 6 mediated recruitment of mesenchymal stem cells to the hypoxic tumor milieu. Exp Cell Res 2010; 316:3417-24; PMID:20633553; http://dx.doi.org/10.1016/j.yexcr.2010.07.002
91. Karnoub AE, Dash AB, Vo AP, Sullivan A, Brooks MW, Bell GW, et al. Mesenchymal stem cells within tumour stroma promote breast cancer metastasis. Nature 2007; 449:557-63; PMID:17914389; http://dx.doi.org/10.1038/nature06188
92. Qian BZ, Pollard JW. Macrophage diversity enhances tumor progression and metastasis. Cell 2010; 141:39-51; PMID:20371344; http://dx.doi.org/10.1016/j. cell.2010.03.014
93. Emery LA, Tripathi A, King C, Kavanah M, Mendez J, Stone MD, et al. Early dysregulation of cell adhesion and extracellular matrix pathways in breast cancer progression. Am J Pathol 2009; 175:1292-302; PMID:19700746; http://dx.doi.org/10.2353/ajpath.2009.090115
94. Esserman LJ, Kumar AS, Herrera AF, Leung J, Au A, Chen YY, et al. Magnetic resonance imaging captures the biology of ductal carcinoma in situ. J Clin Oncol 2006; 24:4603-10; PMID:17008702; http://dx.doi.org/10.1200/JCO.2005. 04.5518
95. Valenzuela M, Julian TB. Ductal carcinoma in situ: biology, diagnosis, and new therapies. Clin Breast Cancer 2007; 7:676-81; PMID:17919347; http://dx.doi.org/10.3816/CBC.2007.n.026
96. Burstein HJ, Polyak K, Wong JS, Lester SC, Kaelin CM. Ductal carcinoma in situ of the breast. N Engl J Med 2004; 350:1430-41; PMID:15070793; http://dx.doi.org/10.1056/NEJMra031301
97. Butcher DT, Alliston T, Weaver VM. A tense situation: forcing tumour progression. Nat Rev Cancer 2009; 9:108-22; PMID:19165226; http://dx.doi.org/10. 1038/nrc2544
98. Ernster VL, Barclay J, Kerlikowske K, Grady D, Henderson C. Incidence of and treatment for ductal carcinoma in situ of the breast. JAMA 1996; 275:913-8; PMID:8598618; http://dx.doi.org/10.1001/jama.1996.03530360023033
99. Gudjonsson T, Adriance MC, Sternlicht MD, Petersen OW, Bissell MJ. Myoepithelial cells: their origin and function in breast morphogenesis and neoplasia. J Mammary Gland Biol Neoplasia 2005; 10:261-72; PMID:16807805; http://dx.doi.org/10.1007/s10911-005-9586-4
100. Hu M, Yao J, Carroll DK, Weremowicz S, Chen H, Carrasco D, et al. Regulation of in situ to invasive breast carcinoma transition. Cancer Cell 2008; 13:394-406; PMID:18455123; http://dx.doi.org/10.1016/j.ccr.2008.03.007
101. Barsky SH, Karlin NJ. Myoepithelial cells: autocrine and paracrine suppressors of breast cancer progression. J Mammary Gland Biol Neoplasia 2005; 10:249-60; PMID:16807804; http://dx.doi.org/10.1007/s10911-005-9585-5
102. Hendrix A, Hume AN. Exosome signaling in mammary gland development and cancer. Int J Dev Biol 2011; 55:879-87; PMID:22161843; http://dx.doi.org/10. 1387/ijdb.113391ah
103. Peinado H, Lavotshkin S, Lyden D. The secreted factors responsible for pre-metastatic niche formation: old sayings and new thoughts. Semin Cancer Biol 2011; 21:139-46; PMID:21251983; http://dx.doi.org/10.1016/j.semcancer.2011.01. 002
104. Leek RD, Landers RJ, Harris AL, Lewis CE. Necrosis correlates with high vascular density and focal macrophage infiltration in invasive carcinoma of the breast. Br J Cancer 1999; 79:991-5; PMID:10070902; http://dx.doi.org/10.1038/sj. bjc.6690158
105. Coussens LM, Werb Z. Inflammation and cancer. Nature 2002; 420:860-7; PMID:12490959; http://dx.doi.org/10.1038/nature01322
106. Tomes L, Emberley E, Niu Y, Troup S, Pastorek J, Strange K, et al. Necrosis and hypoxia in invasive breast carcinoma. Breast Cancer Res Treat 2003; 81:61-9; PMID:14531498; http://dx.doi.org/10.1023/A:1025476722493
107. Dvorak HF. Tumors: wounds that do not heal. Similarities between tumor stroma generation and wound healing. N Engl J Med 1986; 315:1650-9; PMID:3537791
108. Jedeszko C, Victor BC, Podgorski I, Sloane BF. Fibroblast hepatocyte growth factor promotes invasion of human mammary ductal carcinoma in situ. Cancer Res 2009; 69:9148-55; PMID:19920187; http://dx.doi.org/10.1158/0008-5472. CAN-09-1043
109. Kalluri R, Zeisberg M. Fibroblasts in cancer. Nat Rev Cancer 2006; 6:392-401; PMID:16572188; http://dx.doi.org/10.1038/nrc1877
110. Orimo A, Gupta PB, Sgroi DC, Arenzana-Seisdedos F, Delaunay T, Naeem R, et al. Stromal fibroblasts present in invasive human breast carcinomas promote tumor growth and angiogenesis through elevated SDF-1/CXCL12 secretion. Cell 2005; 121:335-48; PMID: 15882617; http://dx.doi.org/10.1016/j.cell.2005.02.034
111. Leek RD, Hunt NC, Landers RJ, Lewis CE, Royds JA, Harris AL. Macrophage infiltration is associated with VEGF and EGFR expression in breast cancer. J Pathol 2000; 190:430-6; PMID:10699991; http://dx.doi.org/10.1002/(SICI)1096- 9896(200003)190:4〈430::AIDPATH538〉3.0.CO;2-6
112. Jänicke F, Schmitt M, Pache L, Ulm K, Harbeck N, Höfler H, et al. Urokinase (uPA) and its inhibitor PAI-1 are strong and independent prognostic factors in node-negative breast cancer. Breast Cancer Res Treat 1993; 24:195-208; PMID:8435475; http://dx.doi.org/10.1007/BF01833260
113. Kessenbrock K, Plaks V, Werb Z. Matrix metalloproteinases: regulators of the tumor microenvironment. Cell 2010; 141:52-67; PMID:20371345; http://dx.doi.org/10.1016/j.cell.2010.03.015
114. Gocheva V, Wang HW, Gadea BB, Shree T, Hunter KE, Garfall AL, et al. IL-4 induces cathepsin protease activity in tumor-associated macrophages to promote cancer growth and invasion. Genes Dev 2010; 24:241-55; PMID:20080943; http://dx.doi.org/10.1101/gad.1874010
115. Tkachenko E, Rhodes JM, Simons M. Syndecans: new kids on the signaling block. Circ Res 2005; 96:488-500; PMID:15774861; http://dx.doi.org/10.1161/01. RES.0000159708.71142.c8
116. Mott JD, Werb Z. Regulation of matrix biology by matrix metalloproteinases. Curr Opin Cell Biol 2004; 16:558-64; PMID:15363807; http://dx.doi.org/10.1016/j.ceb.2004.07.010
117. Hynes RO. The extracellular matrix: not just pretty fibrils. Science 2009; 326:1216-9; PMID:19965464; http://dx.doi.org/10.1126/science.1176009
118. Barcellos-Hoff MH, Ewan KB. Transforming growth factor-beta and breast cancer: Mammary gland development. Breast Cancer Res 2000; 2:92-9; PMID:11250698; http://dx.doi.org/10.1186/bcr40
119. Schenk S, Quaranta V. Tales from the crypt[ic] sites of the extracellular matrix. Trends Cell Biol 2003; 13:366-75; PMID:12837607; http://dx.doi.org/10. 1016/S0962-8924(03)00129-6
120. Giannelli G, Falk-Marzillier J, Schiraldi O, Stetler-Stevenson WG, Quaranta V. Induction of cell migration by matrix metalloprotease-2 cleavage of laminin-5. Science 1997; 277:225-8; PMID:9211848; http://dx.doi.org/10.1126/ science.277.5323.225
121. Schenk S, Hintermann E, Bilban M, Koshikawa N, Hojilla C, Khokha R, et al. Binding to EGF receptor of a laminin-5 EGF-like fragment liberated during MMP-dependent mammary gland involution. J Cell Biol 2003; 161:197-209; PMID:12695504; http://dx.doi.org/10.1083/jcb.200208145
122. Mongiat M, Sweeney SM, San Antonio JD, Fu J, Iozzo RV. Endorepellin, a novel inhibitor of angio-genesis derived from the C terminus of perlecan. J Biol Chem 2003; 278:4238-49; PMID:12435733; http://dx.doi.org/10.1074/jbc.M210445200
123. Yang N, Mosher R, Seo S, Beebe D, Friedl A. Syndecan-1 in breast cancer stroma fibroblasts regulates extracellular matrix fiber organization and carcinoma cell motility. Am J Pathol 2011; 178:325-35; PMID:21224069; http://dx.doi.org/10.1016/j.ajpath.2010.11.039
124. Kumar S, Weaver VM. Mechanics, malignancy, and metastasis: the force journey of a tumor cell. Cancer Metastasis Rev 2009; 28:113-27; PMID:19153673; http://dx.doi.org/10.1007/s10555-008-9173-4
125. Campbell I, Qiu W, Haviv I. Genetic changes in tumour microenvironments. J Pathol 2011; 223:450-8; PMID:21294119; http://dx.doi.org/10.1002/path.2842
126. Liu M, Xu J, Deng H. Tangled fibroblasts in tumor-stroma interactions. Int J Cancer 2011; In press; PMID:21469145
127. Provenzano PP, Inman DR, Eliceiri KW, Knittel JG, Yan L, Rueden CT, et al. Collagen density promotes mammary tumor initiation and progression. BMC Med 2008; 6:11; PMID:18442412; http://dx.doi.org/10.1186/1741-7015-6-11
128. Provenzano PP, Inman DR, Eliceiri KW, Trier SM, Keely PJ. Contact guidance mediated three-dimensional cell migration is regulated by Rho/ROCK-dependent matrix reorganization. Biophys J 2008; 95:5374-84; PMID:18775961; http://dx.doi.org/10.1529/biophysj.108.133116
129. Lopez JI, Kang I, You WK, McDonald DM, Weaver VM. In situ force mapping of mammary gland transformation. Integr Biol (Camb) 2011; 3:910-21; PMID:21842067; http://dx.doi.org/10.1039/c1ib00043h
130. Erler JT, Bennewith KL, Nicolau M, Dornhöfer N, Kong C, Le QT, et al. Lysyl oxidase is essential for hypoxia-induced metastasis. Nature 2006; 440:1222-6; PMID:16642001; http://dx.doi.org/10.1038/nature04695
131. Ioachim E, Charchanti A, Briasoulis E, Karavasilis V, Tsanou H, Arvanitis DL, et al. Immunohistochemical expression of extracellular matrix components tenascin, fibronectin, collagen type IV and laminin in breast cancer: their prognostic value and role in tumour invasion and progression. Eur J Cancer 2002; 38:2362-70; PMID:12460779; http://dx.doi.org/10.1016/S0959-8049(02)00210-1
132. Hancox RA, Allen MD, Holliday DL, Edwards DR, Pennington CJ, Guttery DS, et al. Tumour-associated tenascin-C isoforms promote breast cancer cell invasion and growth by matrix metalloproteinase-dependent and independent mechanisms. Breast Cancer Res 2009; 11:R24; PMID:19405959; http://dx.doi.org/10.1186/bcr2251
133. Adams M, Jones JL, Walker RA, Pringle JH, Bell SC. Changes in tenascin-C isoform expression in invasive and preinvasive breast disease. Cancer Res 2002; 62:3289-97; PMID:12036947
134. Kaczmarek J, Castellani P, Nicolo G, Spina B, Allemanni G, Zardi L. Distribution of oncofetal fibronectin isoforms in normal, hyperplastic and neoplastic human breast tissues. Int J Cancer 1994; 59:11-6; PMID:7927891; http://dx.doi.org/10.1002/ijc.2910590104
135. D'Ovidio MC, Mastracchio A, Marzullo A, Ciabatta M, Pini B, Uccini S, et al. Intratumoral microvessel density and expression of ED-A/ED-B sequences of fibronectin in breast carcinoma. Eur J Cancer 1998; 34:1081-5; PMID:9849458; http://dx.doi.org/10.1016/S0959-8049(98)00041-0
136. Sieweke MH, Thompson NL, Sporn MB, Bissell MJ. Mediation of wound-related Rous sarcoma virus tumor-igenesis by TGF-beta. Science 1990; 248:1656-60; PMID:2163544; http://dx.doi.org/10.1126/science.2163544
137. Dolberg DS, Hollingsworth R, Hertle M, Bissell MJ. Wounding and its role in RSV-mediated tumor formation. Science 1985; 230:676-8; PMID:2996144; http://dx.doi.org/10.1126/science.2996144
138. Dolberg DS, Bissell MJ. Inability of Rous sarcoma virus to cause sarcomas in the avian embryo. Nature 1984; 309:552-6; PMID:6203040; http://dx.doi.org/ 10.1038/309552a0
139. Martins-Green M, Boudreau N, Bissell MJ. Inflammation is responsible for the development of wound-induced tumors in chickens infected with Rous sarcoma virus. Cancer Res 1994; 54:4334-41; PMID:7519120
140. Flanders KC, Wakefield LM. Transforming growth factor-(beta)s and mammary gland involution; functional roles and implications for cancer progression. J Mammary Gland Biol Neoplasia 2009; 14:131-44; PMID:19396528; http://dx.doi.org/10.1007/s10911-009-9122-z
141. O'Brien J, Lyons T, Monks J, Lucia MS, Wilson RS, Hines L, et al. Alternatively activated macrophages and collagen remodeling characterize the postpartum involuting mammary gland across species. Am J Pathol 2010; 176:1241-55; PMID:20110414; http://dx.doi.org/10.2353/ajpath.2010.090735
142. Schedin P. Pregnancy-associated breast cancer and metastasis. Nat Rev Cancer 2006; 6:281-91; PMID:16557280; http://dx.doi.org/10.1038/nrc1839
143. Lyons TR, O'Brien J, Borges VF, Conklin MW, Keely PJ, Eliceiri KW, et al. Postpartum mammary gland involution drives progression of ductal carcinoma in situ through collagen and COX-2. Nat Med 2011; 17:1109-15; PMID:21822285; http://dx.doi.org/10.1038/nm.2416
144. Chang S, Parker SL, Pham T, Buzdar AU, Hursting SD. Inflammatory breast carcinoma incidence and survival: the surveillance, epidemiology, and end results program of the National Cancer Institute, 1975-1992. Cancer 1998; 82:2366-72; PMID:9635529; http://dx.doi.org/10.1002/(SICI)1097-0142(19980615)82: 12〈2366::AID-CNCR10〉3.3.CO;2-B
145. Bonnier P, Romain S, Dilhuydy JM, Bonichon F, Julien JP, Charpin C, et al. Societe Francaise de Senologie et de Pathologie Mammaire Study Group. Influence of pregnancy on the outcome of breast cancer: a case-control study. Int J Cancer 1997; 72:720-7; PMID:9311584; http://dx.doi.org/10.1002/(SICI)1097- 0215(19970904)72:5〈720::AID-IJC3〉3.0.CO;2-U
146. Denardo DG, Brennan DJ, Rexhepaj E, Ruffell B, Shiao SL, Madden SF, et al. Leukocyte Complexity Predicts Breast Cancer Survival and Functionally Regulates Response to Chemotherapy. Cancer Discov 2011; 1:54-67; PMID:22039576; http://dx.doi.org/10.1158/2159-8274.CD-10-0028
147. Farmer P, Bonnefoi H, Anderle P, Cameron D, Wirapati P, Becette V, et al. A stroma-related gene signature predicts resistance to neoadjuvant chemotherapy in breast cancer. Nat Med 2009; 15:68-74; PMID:19122658; http://dx.doi.org/10. 1038/nm.1908
148. Correia AL, Bissell MJ. The tumor microenvironment is a dominant force in multidrug resistance. Drug Resist Updat 2012; 15:39-49; PMID:22335920; http://dx.doi.org/10.1016/j.drup.2012.01.006
149. Weigelt B, Lo AT, Park CC, Gray JW, Bissell MJ. HER2 signaling pathway activation and response of breast cancer cells to HER2-targeting agents is dependent strongly on the 3D microenvironment. Breast Cancer Res Treat 2010; 122:35-43; PMID:19701706; http://dx.doi.org/10.1007/s10549-009-0502-2
150. Shree T, Olson OC, Elie BT, Kester JC, Garfall AL, Simpson K, et al. Macrophages and cathepsin proteases blunt chemotherapeutic response in breast cancer. Genes Dev 2011; 25:2465-79; PMID:22156207; http://dx.doi.org/10.1101/ gad.180331.111
151. Denkert C, Loibl S, Noske A, Roller M, Müller BM, Komor M, et al. Tumor-associated lymphocytes as an independent predictor of response to neoadjuvant chemotherapy in breast cancer. J Clin Oncol 2010; 28:105-13; PMID:19917869; http://dx.doi.org/10.1200/JCO.2009.23.7370
152. Fong PC, Boss DS, Yap TA, Tutt A, Wu P, Mergui-Roelvink M, et al. Inhibition of poly(ADP-ribose) polymerase in tumors from BRCA mutation carriers. N Engl J Med 2009; 361:123-34; PMID:19553641; http://dx.doi.org/10.1056/ NEJMoa0900212
153. Bloom HJ, Richardson WW. Histological grading and prognosis in breast cancer; a study of 1409 cases of which 359 have been followed for 15 years. Br J Cancer 1957; 11:359-77; PMID:13499785; http://dx.doi.org/10.1038/bjc.1957.43
154. Chin K, DeVries S, Fridlyand J, Spellman PT, Roydasgupta R, Kuo WL, et al. Genomic and transcriptional aberrations linked to breast cancer pathophysiologies. Cancer Cell 2006; 10:529-41; PMID:17157792; http://dx.doi.org/10.1016/j.ccr.2006.10.009
155. Ellis IO, Galea M, BroughtonN, Locker A, Blamey RW, Elston CW. Pathological prognostic factors in breast cancer. II. Histological type. Relationship with survival in a large study with long-term follow-up. Histopathology 1992; 20:479-89; PMID:1607149; http://dx.doi.org/10.1111/j.1365- 2559.1992.tb01032.x
156. Miron A, Varadi M, Carrasco D, Li H, Luongo L, Kim HJ, et al. PIK3CA mutations in in situ and invasive breast carcinomas. Cancer Res 2010; 70:5674-8; PMID:20551053; http://dx.doi.org/10.1158/0008-5472.CAN-08-2660
157. Weigelt B, Reis-Filho JS. Histological and molecular types of breast cancer: is there a unifying taxonomy? Nat Rev Clin Oncol 2009; 6:718-30; PMID: 19942925; http://dx.doi.org/10.1038/nrclinonc.2009.166
158. Park SY, Gönen M, Kim HJ, Michor F, Polyak K. Cellular and genetic diversity in the progression of in situ human breast carcinomas to an invasive phenotype. J Clin Invest 2010; 120:636-44; PMID:20101094; http://dx.doi.org/10. 1172/JCI40724
159. Rakha EA, Gill MS, El-Sayed ME, Khan MM, Hodi Z, Blamey RW, et al. The biological and clinical characteristics of breast carcinoma with mixed ductal and lobular morphology. Breast Cancer Res Treat 2009; 114:243-50; PMID:18404368; http://dx.doi.org/10.1007/s10549-008-0007-4
160. Perou CM, Sørlie T, Eisen MB, van de Rijn M, Jeffrey SS, Rees CA, et al. Molecular portraits of human breast tumours. Nature 2000; 406:747-52; PMID:10963602; http://dx.doi.org/10.1038/35021093
161. Sorlie T, Tibshirani R, Parker J, Hastie T, Marron JS, Nobel A, et al. Repeated observation of breast tumor subtypes in independent gene expression data sets. Proc Natl Acad Sci U S A 2003; 100:8418-23; PMID:12829800; http://dx.doi.org/10.1073/pnas.0932692100
162. Sørlie T, Perou CM, Tibshirani R, Aas T, Geisler S, Johnsen H, et al. Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications. Proc Natl Acad Sci U S A 2001; 98:10869-74; PMID:11553815; http://dx.doi.org/10.1073/pnas.191367098
163. Parker JS, Mullins M, Cheang MC, Leung S, Voduc D, Vickery T, et al. Supervised risk predictor of breast cancer based on intrinsic subtypes. J Clin Oncol 2009; 27:1160-7; PMID:19204204; http://dx.doi.org/10.1200/JCO.2008.18.1370
164. Rouzier R, Perou CM, Symmans WF, Ibrahim N, Cristofanilli M, Anderson K, et al. Breast cancer molecular subtypes respond differently to preoperative chemotherapy. Clin Cancer Res 2005; 11:5678-85; PMID:16115903; http://dx.doi.org/10.1158/1078-0432.CCR-04-2421
165. Prat A, Parker JS, Karginova O, Fan C, Livasy C, Herschkowitz JI, et al. Phenotypic and molecular characterization of the claudin-low intrinsic subtype of breast cancer. Breast Cancer Res 2010; 12:R68; PMID:20813035; http://dx.doi.org/10.1186/bcr2635
166. Hennessy BT, Gonzalez-Angulo AM, Stemke-Hale K, Gilcrease MZ, Krishnamurthy S, Lee JS, et al. Characterization of a naturally occurring breast cancer subset enriched in epithelial-to-mesenchymal transition and stem cell characteristics. Cancer Res 2009; 69:4116-24; PMID:19435916; http://dx.doi.org/10.1158/0008-5472.CAN-08-3441
167. Farmer P, Bonnefoi H, Becette V, Tubiana-Hulin M, Fumoleau P, Larsimont D, et al. Identification of molecular apocrine breast tumours by microarray analysis. Oncogene 2005; 24:4660-71; PMID:15897907; http://dx.doi.org/10.1038/ sj.onc.1208561
168. Doane AS, Danso M, Lal P, Donaton M, Zhang L, Hudis C, et al. An estrogen receptor-negative breast cancer subset characterized by a hormonally regulated transcriptional program and response to androgen. Oncogene 2006; 25:3994-4008; PMID:16491124; http://dx.doi.org/10.1038/sj.onc.1209415
169. Sanga S, Broom BM, Cristini V, Edgerton ME. Gene expression meta-analysis supports existence of molecular apocrine breast cancer with a role for androgen receptor and implies interactions with ErbB family. BMC Med Genomics 2009; 2:59; PMID:19747394; http://dx.doi.org/10.1186/1755-8794-2-59
170. Weigelt B, Horlings HM, Kreike B, Hayes MM, Hauptmann M, Wessels LF, et al. Refinement of breast cancer classification by molecular characterization of histological special types. J Pathol 2008; 216:141-50; PMID:18720457; http://dx.doi.org/10.1002/path.2407
171. de Ronde JJ, Hannemann J, Halfwerk H, Mulder L, Straver ME, Vrancken Peeters MJ, et al. Concordance of clinical and molecular breast cancer subtyping in the context of preoperative chemotherapy response. Breast Cancer Res Treat 2010; 119:119-26; PMID:19669409; http://dx.doi.org/10.1007/s10549-009-0499-6
172. Nielsen TO, Parker JS, Leung S, Voduc D, Ebbert M, Vickery T, et al. A comparison of PAM50 intrinsic subtyping with immunohistochemistry and clinical prognostic factors in tamoxifen-treated estrogen receptor-positive breast cancer. Clin Cancer Res 2010; 16:5222-32; PMID:20837693; http://dx.doi.org/10. 1158/1078-0432.CCR-10-1282
173. Weigelt B, Mackay A, A'hern R, Natrajan R, Tan DS, Dowsett M, et al. Breast cancer molecular profiling with single sample predictors: a retrospective analysis. Lancet Oncol 2010; 11:339-49; PMID:20181526; http://dx.doi.org/10. 1016/S1470-2045(10)70008-5
174. Neve RM, Chin K, Fridlyand J, Yeh J, Baehner FL, Fevr T, et al. A collection of breast cancer cell lines for the study of functionally distinct cancer subtypes. Cancer Cell 2006; 10:515-27; PMID:17157791; http://dx.doi.org/10.1016/j.ccr.2006.10.008
175. Rody A, Karn T, Liedtke C, Pusztai L, Ruckhaeberle E, Hanker L, et al. A clinically relevant gene signature in triple negative and basal-like breast cancer. Breast Cancer Res 2011; 13:R97; PMID:21978456; http://dx.doi.org/10. 1186/bcr3035
176. van't Veer LJ, Dai H, van de Vijver MJ, He YD, Hart AA, Mao M, et al. Gene expression profiling predicts clinical outcome of breast cancer. Nature 2002; 415:530-6; PMID:11823860; http://dx.doi.org/10.1038/415530a
177. Dai H, van't Veer L, Lamb J, He YD, Mao M, Fine BM, et al. A cell proliferation signature is a marker of extremely poor outcome in a subpopulation of breast cancer patients. Cancer Res 2005; 65:4059-66; PMID:15899795; http://dx.doi.org/10.1158/0008-5472.CAN-04-3953
178. Wang Y, Klijn JG, Zhang Y, Sieuwerts AM, Look MP, Yang F, et al. Gene-expression profiles to predict distant metastasis of lymph-node-negative primary breast cancer. Lancet 2005; 365:671-9; PMID:15721472
179. Sotiriou C, Wirapati P, Loi S, Harris A, Fox S, Smeds J, et al. Gene expression profiling in breast cancer: understanding the molecular basis of histologic grade to improve prognosis. J Natl Cancer Inst 2006; 98:262-72; PMID:16478745; http://dx.doi.org/10.1093/jnci/djj052
180. Liu R, Wang X, Chen GY, Dalerba P, Gurney A, Hoey T, et al. The prognostic role of a gene signature from tumorigenic breast-cancer cells. N Engl J Med 2007; 356:217-26; PMID:17229949; http://dx.doi.org/10.1056/NEJMoa063994
181. Fournier MV, Martin KJ, Kenny PA, Xhaja K, Bosch I, Yaswen P, et al. Gene expression signature in organized and growth-arrested mammary acini predicts good outcome in breast cancer. Cancer Res 2006; 66:7095-102; PMID:16849555; http://dx.doi.org/10.1158/0008-5472.CAN-06-0515
182. Martin KJ, Patrick DR, Bissell MJ, Fournier MV. Prognostic breast cancer signature identified from 3D culture model accurately predicts clinical outcome across independent datasets. PLoS One 2008; 3:e2994; PMID:18714348; http://dx.doi.org/10.1371/journal.pone.0002994
183. Fan C, Oh DS, Wessels L, Weigelt B, Nuyten DS, Nobel AB, et al. Concordance among gene-expression-based predictors for breast cancer. N Engl J Med 2006; 355:560-9; PMID:16899776; http://dx.doi.org/10.1056/NEJMoa052933
184. Tian S, Roepman P, Van't Veer LJ, Bernards R, de Snoo F, Glas AM. Biological functions of the genes in the mammaprint breast cancer profile reflect the hallmarks of cancer. Biomark Insights 2010; 5:129-38; PMID:21151591
185. van de Vijver MJ, He YD, van't Veer LJ, Dai H, Hart AA, Voskuil DW, et al. A gene-expression signature as a predictor of survival in breast cancer. N Engl J Med 2002; 347:1999-2009; PMID:12490681; http://dx.doi.org/10.1056/ NEJMoa021967
186. Buyse M, Loi S, van't Veer L, Viale G, Delorenzi M, Glas AM, et al. TRANSBIG Consortium. Validation and clinical utility of a 70-gene prognostic signature for women with node-negative breast cancer. J Natl Cancer Inst 2006; 98:1183-92; PMID:16954471; http://dx.doi.org/10.1093/jnci/djj329
187. Bueno-de-Mesquita JM, Linn SC, Keijzer R, Wesseling J, Nuyten DS, van Krimpen C, et al. Validation of 70-gene prognosis signature in node-negative breast cancer. Breast Cancer Res Treat 2009; 117:483-95; PMID:18819002; http://dx.doi.org/10.1007/s10549-008-0191-2
188. Ishitobi M, Goranova TE, Komoike Y, Motomura K, Koyama H, Glas AM, et al. Clinical utility of the 70-gene MammaPrint profile in a Japanese population. Jpn J Clin Oncol 2010; 40:508-12; PMID:20110242; http://dx.doi.org/10.1093/jjco/ hyp195
189. Wittner BS, Sgroi DC, Ryan PD, Bruinsma TJ, Glas AM, Male A, et al. Analysis of the MammaPrint breast cancer assay in a predominantly postmenopausal cohort. Clin Cancer Res 2008; 14:2988-93; PMID: 18483364; http://dx.doi.org/10. 1158/1078-0432.CCR-07-4723
190. Knauer M, Cardoso F, Wesseling J, Bedard PL, Linn SC, Rutgers EJ, et al. Identification of a low-risk subgroup of HER-2-positive breast cancer by the 70-gene prognosis signature. Br J Cancer 2010; 103:1788-93; PMID:21081926; http://dx.doi.org/10.1038/sj.bjc.6605916
191. Glas AM, Floore A, Delahaye LJ, Witteveen AT, Pover RC, Bakx N, et al. Converting a breast cancer microarray signature into a high-throughput diagnostic test. BMC Genomics 2006; 7:278; PMID:17074082; http://dx.doi.org/10. 1186/1471-2164-7-278
192. Cardoso F, Van't Veer L, Rutgers E, Loi S, Mook S, Piccart-Gebhart MJ. Clinical application of the 70-gene profile: the MINDACT trial. J Clin Oncol 2008; 26:729-35; PMID:18258980; http://dx.doi.org/10.1200/JCO.2007.14.3222
193. Cardoso F, Piccart-Gebhart M, Van't Veer L, Rutgers E, TRANSBIG Consortium. The MINDACT trial: the first prospective clinical validation of a genomic tool. Mol Oncol 2007; 1:246-51; PMID:19383299; http://dx.doi.org/10. 1016/j.molonc.2007.10.004
194. Chang HY, Sneddon JB, Alizadeh AA, Sood R, West RB, Montgomery K, et al. Gene expression signature of fibroblast serum response predicts human cancer progression: similarities between tumors and wounds. PLoS Biol 2004; 2:E7; PMID:14737219; http://dx.doi.org/10.1371/journal.pbio.0020007
195. Chang HY, Nuyten DS, Sneddon JB, Hastie T, Tibshirani R, Sørlie T, et al. Robustness, scalability, and integration of a wound-response gene expression signature in predicting breast cancer survival. Proc Natl Acad Sci U S A 2005; 102:3738-43; PMID:15701700; http://dx.doi.org/10.1073/pnas.0409462102
196. Boersma BJ, Reimers M, Yi M, Ludwig JA, Luke BT, Stephens RM, et al. A stromal gene signature associated with inflammatory breast cancer. Int J Cancer 2008; 122:1324-32; PMID:17999412; http://dx.doi.org/10.1002/ijc.23237
197. Casey T, Bond J, Tighe S, Hunter T, Lintault L, Patel O, et al. Molecular signatures suggest a major role for stromal cells in development of invasive breast cancer. Breast Cancer Res Treat 2009; 114:47-62; PMID:18373191; http://dx.doi.org/10.1007/s10549-008-9982-8
198. Kristensen VN, Vaske CJ, Ursini-Siegel J, Van Loo P, Nordgard SH, Sachidanandam R, et al. Integrated molecular profiles of invasive breast tumors and ductal carcinoma in situ (DCIS) reveal differential vascular and interleukin signaling. Proc Natl Acad Sci U S A 2012; 109:2802-7; PMID:21908711; http://dx.doi.org/10.1073/pnas.1108781108
199. Myhre S, Mohammed H, Tramm T, Alsner J, Finak G, Park M, et al. In silico ascription of gene expression differences to tumor and stromal cells in a model to study impact on breast cancer outcome. PLoS One 2010; 5:e14002; PMID:21124964; http://dx.doi.org/10.1371/journal.pone.0014002
200. Bianchini G, Qi Y, Alvarez RH, Iwamoto T, Coutant C, Ibrahim NK, et al. Molecular anatomy of breast cancer stroma and its prognostic value in estrogen receptor-positive and -negative cancers. J Clin Oncol 2010; 28:4316-23; PMID:20805453; http://dx.doi.org/10.1200/JCO.2009.27.2419
201. Finak G, Bertos N, Pepin F, Sadekova S, Souleimanova M, Zhao H, et al. Stromal gene expression predicts clinical outcome in breast cancer. Nat Med 2008; 14:518-27; PMID:18438415; http://dx.doi.org/10.1038/nm1764
202. Bergamaschi A, Tagliabue E, Sørlie T, Naume B, Triulzi T, Orlandi R, et al. Extracellular matrix signature identifies breast cancer subgroups with different clinical outcome. J Pathol 2008; 214:357-67; PMID:18044827; http://dx.doi.org/10.1002/path.2278
203. Troester MA, Lee MH, Carter M, Fan C, Cowan DW, Perez ER, et al. Activation of host wound responses in breast cancer microenvironment. Clin Cancer Res 2009; 15:7020-8; PMID:19887484; http://dx.doi.org/10.1158/1078-0432. CCR-09-1126
204. West RB, Nuyten DS, Subramanian S, Nielsen TO, Corless CL, Rubin BP, et al. Determination of stromal signatures in breast carcinoma. PLoS Biol 2005; 3:e187; PMID:15869330; http://dx.doi.org/10.1371/journal.pbio.0030187
205. LaBarge MA, Nelson CM, Villadsen R, Fridriksdottir A, Ruth JR, Stampfer MR, et al. Human mammary progenitor cell fate decisions are products of interactions with combinatorial microenvironments. Integr Biol (Camb) 2009; 1:70-9; PMID:20023793; http://dx.doi.org/10.1039/b816472j
206. Villadsen R, Fridriksdottir AJ, Rønnov-Jessen L, Gudjonsson T, Rank F, LaBarge MA, et al. Evidence for a stem cell hierarchy in the adult human breast. J Cell Biol 2007; 177:87-101; PMID:17420292; http://dx.doi.org/10.1083/ jcb.200611114
207. Kim J, Villadsen R, Sørlie T, Fogh L, Grønlund SZ, Fridriksdottir AJ, et al. Tumor initiating but differentiated luminal-like breast cancer cells are highly invasive in the absence of basal-like activity. Proc Natl Acad Sci U S A 2012; 109:6124-9; PMID:22454501; http://dx.doi.org/10. 1073/pnas.1203203109
208. Petersen OW, Polyak K. Stem cells in the human breast. Cold Spring Harb Perspect Biol 2010; 2:a003160; PMID:20452965; http://dx.doi.org/10.1101/ cshperspect.a003160