Seminars in Oncology
Volume 35, Issue 1 , Pages 33-40 , February 2008

Pathologic Aspects of Inflammatory Breast Cancer: Part 2. Biologic Insights Into Its Aggressive Phenotype

  • Yun Gong

      Affiliations

    • Corresponding Author InformationAddress correspondence to Yun Gong, MD, Department of Pathology, Unit 53, The University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030.

References 

  1. Jaiyesimi IA, Buzdar AU, Hortobagyi G. Inflammatory breast cancer: a review. J Clin Oncol. 1992;10:1014–1024
  2. Anderson WF, Chu KC, Chang S. Inflammatory breast carcinoma and noninflammatory locally advanced breast carcinoma: distinct clinicopathologic entities?. J Clin Oncol. 2003;21:2254–2259
  3. Kleer CG, van Golen KL, Merajver SD. Molecular biology of breast cancer metastasis (Inflammatory breast cancer: clinical syndrome and molecular determinants). Breast Cancer Res. 2000;2:423–429
  4. Hance KW, Anderson WF, Devesa SS, et al. Trends in inflammatory breast carcinoma incidence and survival: the Surveillance, Epidemiology, and End Results program at the National Cancer Institute. J Natl Cancer Inst. 2005;97:966–975
  5. Levine PH, Steinhorn SC, Ries LG, et al. Inflammatory breast cancer: the experience of the Surveillance, Epidemiology, and End Results (SEER) program. J Natl Cancer Inst. 1985;74:291–297
  6. Bonnefoi H, Diebold-Berger S, Therasse P, et al. Locally advanced/inflammatory breast cancers treated with intensive epirubicin-based neoadjuvant chemotherapy: are there molecular markers in the primary tumour that predict for 5-year clinical outcome?. Ann Oncol. 2003;14:406–413
  7. Kleer CG, van Golen KL, Braun T, et al. Persistent E-cadherin expression in inflammatory breast cancer. Mod Pathol. 2001;14:458–464
  8. Paradiso A, Tommasi S, Brandi M, et al. Cell kinetics and hormonal receptor status in inflammatory breast carcinoma (Comparison with locally advanced disease). Cancer. 1989;64:1922–1927
  9. Turpin E, Bieche I, Bertheau P, et al. Increased incidence of ERBB2 overexpression and TP53 mutation in inflammatory breast cancer. Oncogene. 2002;21:7593–7597
  10. Bieche I, Lerebours F, Tozlu S, et al. Molecular profiling of inflammatory breast cancer: identification of a poor-prognosis gene expression signature. Clin Cancer Res. 2004;10:6789–6795
  11. Delarue JC, May-Levin F, Mouriesse H, et al. Oestrogen and progesterone cytosolic receptors in clinically inflammatory tumours of the human breast. Br J Cancer. 1981;44:911–916
  12. Bonnier P, Charpin C, Lejeune C, et al. Inflammatory carcinomas of the breast: a clinical, pathological, or a clinical and pathological definition?. Int J Cancer. 1995;62:382–385
  13. Takeichi M. Cadherin cell adhesion receptors as a morphogenetic regulator. Science. 1991;251:1451–1455
  14. Gamallo C, Palacios J, Suarez A, et al. Correlation of E-cadherin expression with differentiation grade and histological type in breast carcinoma. Am J Pathol. 1993;142:987–993
  15. Oka H, Shiozaki H, Kobayashi K, et al. Expression of E-cadherin cell adhesion molecules in human breast cancer tissues and its relationship to metastasis. Cancer Res. 1993;53:1696–1701
  16. Bukholm IK, Nesland JM, Karesen R, et al. E-cadherin and alpha-, beta-, and gamma-catenin protein expression in relation to metastasis in human breast carcinoma. J Pathol. 1998;185:262–266
  17. Hunt NC, Douglas-Jones AG, Jasani B, et al. Loss of E-cadherin expression associated with lymph node metastases in small breast carcinomas. Virchows Arch. 1997;430:285–289
  18. Siitonen SM, Kononen JT, Helin HJ, et al. Reduced E-cadherin expression is associated with invasiveness and unfavorable prognosis in breast cancer. Am J Clin Pathol. 1996;105:394–402
  19. Heimann R, Lan F, McBride R, et al. Separating favorable from unfavorable prognostic markers in breast cancer: the role of E-cadherin. Cancer Res. 2000;60:298–304
  20. Christofori G, Semb H. The role of the cell-adhesion molecule E-cadherin as a tumour-suppressor gene. Trends Biochem Sci. 1999;24:73–76
  21. Alpaugh ML, Tomlinson JS, Shao ZM, et al. A novel human xenograft model of inflammatory breast cancer. Cancer Res. 1999;59:5079–5084
  22. Tomlinson JS, Alpaugh ML, Barsky SH. An intact overexpressed E-cadherin/alpha,beta-catenin axis characterizes the lymphovascular emboli of inflammatory breast carcinoma. Cancer Res. 2001;61:5231–5241
  23. Hoffmeyer MR, Wall KM, Dharmawardhane SF. In vitro analysis of the invasive phenotype of SUM 149, an inflammatory breast cancer cell line. Cancer Cell Int. 2005;5:11
  24. Dong HM, Liu G, Hou YF, et al. Dominant-negative E-cadherin inhibits the invasiveness of inflammatory breast cancer cells in vitro. J Cancer Res Clin Oncol. 2007;133:83–92
  25. Colpaert CG, Vermeulen PB, Benoy I, et al. Inflammatory breast cancer shows angiogenesis with high endothelial proliferation rate and strong E-cadherin expression. Br J Cancer. 2003;88:718–725
  26. Liotta LA, Saidel MG, Kleinerman J. The significance of hematogenous tumor cell clumps in the metastatic process. Cancer Res. 1976;36:889–894
  27. Moore DH, Rouse MB, Massenburg GS, et al. Description of a spheroid model for the study of radiation and chemotherapy effects on hypoxic tumor cell populations. Gynecol Oncol. 1992;47:44–47
  28. Alpaugh ML, Tomlinson JS, Kasraeian S, et al. Cooperative role of E-cadherin and sialyl-Lewis X/A-deficient MUC1 in the passive dissemination of tumor emboli in inflammatory breast carcinoma. Oncogene. 2002;21:3631–3643
  29. Alpaugh ML, Tomlinson JS, Ye Y, et al. Relationship of sialyl-Lewis(x/a) underexpression and E-cadherin overexpression in the lymphovascular embolus of inflammatory breast carcinoma. Am J Pathol. 2002;161:619–628
  30. Charafe-Jauffret E, Tarpin C, Bardou VJ, et al. Immunophenotypic analysis of inflammatory breast cancers: identification of an ‘inflammatory signature’. J Pathol. 2004;202:265–273
  31. Folkman J. What is the evidence that tumors are angiogenesis dependent?. J Natl Cancer Inst. 1990;82:4–6
  32. Horak ER, Leek R, Klenk N, et al. Angiogenesis, assessed by platelet/endothelial cell adhesion molecule antibodies, as indicator of node metastases and survival in breast cancer. Lancet. 1992;340:1120–1124
  33. Weidner N, Folkman J, Pozza F, et al. Tumor angiogenesis: a new significant and independent prognostic indicator in early-stage breast carcinoma. J Natl Cancer Inst. 1992;84:1875–1887
  34. Gasparini G, Weidner N, Bevilacqua P, et al. Tumor microvessel density, p53 expression, tumor size, and peritumoral lymphatic vessel invasion are relevant prognostic markers in node-negative breast carcinoma. J Clin Oncol. 1994;12:454–466
  35. Toi M, Kashitani J, Tominaga T. Tumor angiogenesis is an independent prognostic indicator in primary breast carcinoma. Int J Cancer. 1993;55:371–374
  36. Visscher DW, Smilanetz S, Drozdowicz S, et al. Prognostic significance of image morphometric microvessel enumeration in breast carcinoma. Anal Quant Cytol Histol. 1993;15:88–92
  37. McCarthy NJ, Yang X, Linnoila IR, et al. Microvessel density, expression of estrogen receptor alpha, MIB-1, p53, and c-erbB-2 in inflammatory breast cancer. Clin Cancer Res. 2002;8:3857–3862
  38. Shirakawa K, Tsuda H, Heike Y, et al. Absence of endothelial cells, central necrosis, and fibrosis are associated with aggressive inflammatory breast cancer. Cancer Res. 2001;61:445–451
  39. Shirakawa K, Shibuya M, Heike Y, et al. Tumor-infiltrating endothelial cells and endothelial precursor cells in inflammatory breast cancer. Int J Cancer. 2002;99:344–351
  40. Van der Auwera I, Van Laere SJ, Van den Eynden GG, et al. Increased angiogenesis and lymphangiogenesis in inflammatory versus noninflammatory breast cancer by real-time reverse transcriptase-PCR gene expression quantification. Clin Cancer Res. 2004;10:7965–7971
  41. Van der Auwera I, Van den Eynden GG, Colpaert CG, et al. Tumor lymphangiogenesis in inflammatory breast carcinoma: a histomorphometric study. Clin Cancer Res. 2005;11:7637–7642
  42. Stacker SA, Achen MG, Jussila L, et al. Lymphangiogenesis and cancer metastasis. Nat Rev Cancer. 2002;2:573–583
  43. Achen MG, Jeltsch M, Kukk E, et al. Vascular endothelial growth factor D (VEGF-D) is a ligand for the tyrosine kinases VEGF receptor 2 (Flk1) and VEGF receptor 3 (Flt4). Proc Natl Acad Sci U S A. 1998;95:548–553
  44. Saharinen P, Tammela T, Karkkainen MJ, et al. Lymphatic vasculature: development, molecular regulation and role in tumor metastasis and inflammation. Trends Immunol. 2004;25:387–395
  45. Skobe M, Hawighorst T, Jackson DG, et al. Induction of tumor lymphangiogenesis by VEGF-C promotes breast cancer metastasis. Nat Med. 2001;7:192–198
  46. Stacker SA, Caesar C, Baldwin ME, et al. VEGF-D promotes the metastatic spread of tumor cells via the lymphatics. Nat Med. 2001;7:186–191
  47. He Y, Rajantie I, Pajusola K, et al. Vascular endothelial cell growth factor receptor 3-mediated activation of lymphatic endothelium is crucial for tumor cell entry and spread via lymphatic vessels. Cancer Res. 2005;65:4739–4746
  48. Tammela T, Enholm B, Alitalo K, et al. The biology of vascular endothelial growth factors. Cardiovasc Res. 65:550-63.
  49. He Y, Kozaki K, Karpanen T, et al. Suppression of tumor lymphangiogenesis and lymph node metastasis by blocking vascular endothelial growth factor receptor 3 signaling. J Natl Cancer Inst. 2002;94:819–825
  50. Kurebayashi J, Otsuki T, Kunisue H, et al. Expression of vascular endothelial growth factor (VEGF) family members in breast cancer. Jpn J Cancer Res. 1999;90:977–981
  51. Harvey HA, Lipton A, Lawrence BV, et al. Estrogen receptor status in inflammatory breast carcinoma. J Surg Oncol. 1982;21:42–44
  52. Nguyen DM, Sam K, Tsimelzon A, et al. Molecular heterogeneity of inflammatory breast cancer: a hyperproliferative phenotype. Clin Cancer Res. 2006;12:5047–5054
  53. Van den Eynden GG, Van der Auwera I, Van Laere S, et al. Validation of a tissue microarray to study differential protein expression in inflammatory and non-inflammatory breast cancer. Breast Cancer Res Treat. 2004;85:13–22
  54. Aziz SA, Pervez S, Khan S, et al. Case control study of prognostic markers and disease outcome in inflammatory carcinoma breast: a unique clinical experience. Breast J. 2001;7:398–404
  55. Riou G, Le MG, Travagli JP, et al. Poor prognosis of p53 gene mutation and nuclear overexpression of p53 protein in inflammatory breast carcinoma. J Natl Cancer Inst. 1993;85:1765–1767
  56. Fields JN, Perez CA, Kuske RR, et al. Inflammatory carcinoma of the breast: treatment results on 107 patients. Int J Radiat Oncol Biol Phys. 1989;17:249–255
  57. Palangie T, Mosseri V, Mihura J, et al. Prognostic factors in inflammatory breast cancer and therapeutic implications. Eur J Cancer. 1994;30A:921–927
  58. Lerebours F, Bertheau P, Bieche I, et al. Two prognostic groups of inflammatory breast cancer have distinct genotypes. Clin Cancer Res. 2003;9:4184–4189
  59. Kaufmann M. Review of known prognostic variables. Recent Results Cancer Res Fortschritte der Krebsforschung. 1996;140:77–87
  60. Guerin M, Gabillot M, Mathieu MC, et al. Structure and expression of c-erbB-2 and EGF receptor genes in inflammatory and non-inflammatory breast cancer: prognostic significance. Int J Cancer. 1989;43:201–208
  61. Guerin M, Sheng ZM, Andrieu N, et al. Strong association between c-myb and oestrogen-receptor expression in human breast cancer. Oncogene. 1990;5:131–135
  62. Parton M, Dowsett M, Ashley S, et al. High incidence of HER-2 positivity in inflammatory breast cancer. Breast. 2004;13:97–103
  63. Charpin C, Bonnier P, Khouzami A, et al. Inflammatory breast carcinoma: an immunohistochemical study using monoclonal anti-pHER-2/neu, pS2, cathepsin, ER and PR. Anticancer Res. 1992;12:591–597
  64. Sawaki M, Ito Y, Akiyama F, et al. High prevalence of HER-2/neu and p53 overexpression in inflammatory breast cancer. Breast Cancer. 2006;13:172–178
  65. Foekens JA, Rio MC, Seguin P, van Putten WL, Fauque J, Nap M, et al. Prediction of relapse and survival in breast cancer patients by pS2 protein status. Cancer Res. 1990;50:3832–3837
  66. Prost S, Le MG, Douc-Rasy S, et al. Association of c-erbB2-gene amplification with poor prognosis in non-inflammatory breast carcinomas but not in carcinomas of the inflammatory type. Int J Cancer. 1994;58:763–768
  67. Blondal JA, Benchimol S. The role of p53 in tumor progression. Semin Cancer Biol. 1994;5:177–186
  68. Nigro JM, Baker SJ, Preisinger AC, et al. Mutations in the p53 gene occur in diverse human tumour types. Nature. 1989;342:705–708
  69. Moll UM, Riou G, Levine AJ. Two distinct mechanisms alter p53 in breast cancer: mutation and nuclear exclusion. Proc Natl Acad Sci U S A. 1992;89:7262–7266
  70. Aas T, Borresen AL, Geisler S, et al. Specific P53 mutations are associated with de novo resistance to doxorubicin in breast cancer patients. Nat Med. 1996;2:811–814
  71. Feki A, Irminger-Finger I. Mutational spectrum of p53 mutations in primary breast and ovarian tumors. Crit Rev Oncol Hematol. 2004;52:103–116
  72. Yonish-Rouach E, Resnitzky D, Lotem J, et al. Wild-type p53 induces apoptosis of myeloid leukaemic cells that is inhibited by interleukin-6. Nature. 1991;352:345–347
  73. Gonzalez-Angulo AM, Sneige N, Buzdar AU, et al. p53 expression as a prognostic marker in inflammatory breast cancer. Clin Cancer Res. 2004;10:6215–6221
  74. Faille A, De Cremoux P, Extra JM, et al. p53 mutations and overexpression in locally advanced breast cancers. Br J Cancer. 1994;69:1145–1150
  75. Kandioler-Eckersberger D, Ludwig C, Rudas M, et al. TP53 mutation and p53 overexpression for prediction of response to neoadjuvant treatment in breast cancer patients. Clin Cancer Res. 2000;6:50–56
  76. Resetkova E, Gonzalez-Angulo AM, Sneige N, et al. Prognostic value of P53, MDM-2, and MUC-1 for patients with inflammatory breast carcinoma. Cancer. 2004;101:913–917
  77. van Golen KL, Davies S, Wu ZF, et al. A novel putative low-affinity insulin-like growth factor-binding protein, LIBC (lost in inflammatory breast cancer), and RhoC GTPase correlate with the inflammatory breast cancer phenotype. Clin Cancer Res. 1999;5:2511–2519
  78. van Golen KL, Wu ZF, Qiao XT, et al. RhoC GTPase, a novel transforming oncogene for human mammary epithelial cells that partially recapitulates the inflammatory breast cancer phenotype. Cancer Res. 2000;60:5832–5838
  79. Kleer CG, van Golen KL, Zhang Y, et al. Characterization of RhoC expression in benign and malignant breast disease: a potential new marker for small breast carcinomas with metastatic ability. Am J Pathol. 2002;160:579–584
  80. Kleer CG, Griffith KA, Sabel MS, et al. RhoC-GTPase is a novel tissue biomarker associated with biologically aggressive carcinomas of the breast. Breast Cancer Res Treat. 2005;93:101–110
  81. van Golen KL, Wu ZF, Qiao XT, et al. RhoC GTPase overexpression modulates induction of angiogenic factors in breast cells. Neoplasia. 2000;2:418–425
  82. Wu M, Wu ZF, Kumar-Sinha C, et al. RhoC induces differential expression of genes involved in invasion and metastasis in MCF10A breast cells. Breast Cancer Res Treat. 2004;84:3–12
  83. Kleer CG, Zhang Y, Pan Q, et al. WISP3 is a novel tumor suppressor gene of inflammatory breast cancer. Oncogene. 2002;21:3172–3180
  84. Kleer CG, Zhang Y, Pan Q, et al. WISP3 and RhoC guanosine triphosphatase cooperate in the development of inflammatory breast cancer. Breast Cancer Res. 2004;6:R110–R115
  85. Van Laere S, Van der Auwera I, Van den Eynden GG, et al. Distinct molecular signature of inflammatory breast cancer by cDNA microarray analysis. Breast Cancer Res Treat. 2005;93:237–246
  86. Van Laere SJ, Van der Auwera I, Van den Eynden GG, et al. Nuclear factor-kappaB signature of inflammatory breast cancer by cDNA microarray validated by quantitative real-time reverse transcription-PCR, immunohistochemistry, and nuclear factor-kappaB DNA-binding. Clin Cancer Res. 2006;12:3249–3256
  87. Gonzalez-Angulo AM, Guarneri V, Gong Y, et al. Downregulation of the cyclin-dependent kinase inhibitor p27kip1 might correlate with poor disease-free and overall survival in inflammatory breast cancer. Clin Breast Cancer. 2006;7:326–330
  88. Andre F, Cabioglu N, Assi H, et al. Expression of chemokine receptors predicts the site of metastatic relapse in patients with axillary node positive primary breast cancer. Ann Oncol. 2006;17:945–951
  89. Cabioglu N, Sahin A, Doucet M, et al. Chemokine receptor CXCR4 expression in breast cancer as a potential predictive marker of isolated tumor cells in bone marrow. Clin Exp Metastasis. 2005;22:39–46
  90. Cabioglu N, Yazici MS, Arun B, et al. CCR7 and CXCR4 as novel biomarkers predicting axillary lymph node metastasis in T1 breast cancer. Clin Cancer Res. 2005;11:5686–5693
  91. Cabioglu N, Gong Y, Islam R, et al. Expression of growth factor and chemokine receptors: new insights in the biology of inflammatory breast cancer. Ann Oncol. 2007;18:1021–1029
  92. Gong Y, Gonzalez-Angulo AM, Broglio K, et al. Expression of Notch-1 and β-catenin: defining the molecular portrait of inflammatory breast cancer. Breast Cancer Res Treat. 2006;100:S299
  93. Lerebours F, Bertheau P, Bieche I, et al. Evidence of chromosome regions and gene involvement in inflammatory breast cancer. Int J Cancer. 2002;102:618–622
  94. Forozan F, Veldman R, Ammerman CA, et al. Molecular cytogenetic analysis of 11 new breast cancer cell lines. Br J Cancer. 81:1328-34.
  95. Bertucci F, Finetti P, Rougemont J, et al. Gene expression profiling for molecular characterization of inflammatory breast cancer and prediction of response to chemotherapy. Cancer Res. 2004;64:8558–8565
  96. Bertucci F, Finetti P, Rougemont J, et al. Gene expression profiling identifies molecular subtypes of inflammatory breast cancer. Cancer Res. 2005;65:2170–2178
  97. Van Laere SJ, Van den Eynden GG, Van der Auwera I, et al. Identification of cell-of-origin breast tumor subtypes in inflammatory breast cancer by gene expression profiling. Breast Cancer Res Treat. 2006;95:243–255

PII: S0093-7754(07)00239-4

doi: 10.1053/j.seminoncol.2007.11.014

Seminars in Oncology
Volume 35, Issue 1 , Pages 33-40 , February 2008

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