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The Epidermal Growth Factor Receptor Pathway as a Selective Molecular-Targeted Treatment in Human Breast Cancer

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Part of the book series: Cancer Drug Discovery and Development ((CDD&D))

Abstract

The regulation of normal breast development is dependent on several hormones. Among these hormones, estrogens play an essential role in the control of normal mammary development and in the etiology and progression of breast cancer.

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References

  1. Dickson RB, Lippman ME. Growth factors in breast cancer. Endocr Rev 1995;16:559–589.

    Article  PubMed  CAS  Google Scholar 

  2. Normanno N, Ciardiello F. EGF related peptides in the pathophysiology of the mammary gland. J Mammary Gland Biol Neoplasia 1997;2:143–151.

    Article  PubMed  CAS  Google Scholar 

  3. Osbore CK, Hamilton B, Titus G, Livingston RB. Epidermal growth factor stimulation of human breast cancer cells in culture. Cancer Res 1980;40:2361–2366.

    Google Scholar 

  4. Cohen S. Isolation of mouse submaxillary gland protein accelerating incisor eruptin and eyelid opening in the new-born animal. J Biol Chem 1962;237:1555–1562.

    PubMed  CAS  Google Scholar 

  5. Gregory H. Isolation and structure of urogastrone and its relationship to epidermal growth factor. Nature 1975;257:325–327.

    Article  PubMed  CAS  Google Scholar 

  6. Mroczkowski B, Reich M, Chen K, Bell GI, Cohen S. Recombinant human EGF precursor is a glycosylated membrane protein with biological activity. Mol Cell Biol 1989;9:2771–2778.

    PubMed  CAS  Google Scholar 

  7. Murphy LC, Murphy LJ, Dubik D, Bell GI, Shiu RPC. Epidermal growth factor gene expression in human breast cancer cells: regulation of expression by progestins. Cancer Res 1988;48:4555–4560.

    PubMed  CAS  Google Scholar 

  8. Salomon DS, Brandt R, Ciardiello F, Normanno N. Epidermal growth factor-related peptides and their receptors in human malignancies. Crit Rev Oncol/Haematol 1995;19:183–232.

    Article  CAS  Google Scholar 

  9. Martinez-Lacaci I, Bianco C, De Santis M, Salomon DS. Epidermal growth factor related peptides and their cognate receptors in breast cancer. In: Breast Cancer: Molecular Genetics, Pathogenesis, and Therapeutics.

    Google Scholar 

  10. Klapper L, Glathe S, Vaisman N, et al. The ErbB-2/HER2 oncoprotein of human carcinomas may function solely as a shared coreceptor for multiple stroma-derived growth factor. Proc Natl Acad Sci USA 1999;96:4995–5000.

    Article  PubMed  CAS  Google Scholar 

  11. Riese DJ II, van Raaij TM, Plowman GD, Andrews GC, Stern DF. Cellular response to neuregulins is governed by complex interactions of the erbB receptor family. Mol Cell Biol 1995;15:5770–5776.

    PubMed  CAS  Google Scholar 

  12. Salomon DS, Gullick W. The erbB family of receptors and their ligands: multiple targets for therapy. Signal 2001;2:4–11.

    Article  Google Scholar 

  13. Kokai Y, Meyers JN, Wada T, et al. Synergistic interaction of p1 85 c-neu and the EGF receptor leads to transformation of rodent fibroblasts. Cell 1989;58:287–292.

    Article  PubMed  CAS  Google Scholar 

  14. Kuranagaran D, Tzahar E, Beerli R, et al. ErbB2 is a common auxiliary subunit of NDF and EGF receptors: implications for breast cancer. EMBO J 1996;15:254–264.

    Google Scholar 

  15. Guy PM, Platko JV, Cantley LC, Cerione RA, Carraway KL III. Insect cell expressed p180erbB3 possesses an impaired tyrosine kinase activity. Proc Natl AcadSci USA 1994;91:8132–8136.

    Article  CAS  Google Scholar 

  16. Stem DF, Kamps MP. EGF-stimulated tyrosine phosphorylation of p185neu: a potential model for receptor interactions. EMBO J 1988;7:995–1001.

    Google Scholar 

  17. Yang Y, Spitzer E, Meyer D, et al. Sequential requirement of hepatocyte growth factor and neuregulin in the morphogenesis and differentiation of the mammary gland. J Cell Biol 1995;131:215–226.

    Article  PubMed  CAS  Google Scholar 

  18. Sebastian J, Richards RG, Walker MP, et al. Activation and function of the epidermal growth factor receptor and erbB2 during mammary gland morphogenesis. Cell Growth Differ 1998;9:777–785.

    PubMed  CAS  Google Scholar 

  19. Schroeder JA, Lee DC. Dynamic expression and activation of ERBB receptors in the developing mouse mammary gland. Cell Growth Differ 1998;9:451–464.

    PubMed  CAS  Google Scholar 

  20. Xie W, Paterson A, Chin E, Nabell L, Kudlow J. Targeted expression of a dominant negative epidermal growth factor receptor in mammary gland of transgenic mice inhibits pubertal mammary ductal development. Mol Endocrinol 1997;1:1766–1781.

    Article  Google Scholar 

  21. Jones F, Sterm D. Expression of dominant negative ErbB2 in the mammary gland of transgenic mice reveals a rule in lobuloalveolar development and lactation. Oncogene 1999;18:3481–3490.

    Article  PubMed  CAS  Google Scholar 

  22. Jones FE, Welte T, Fu X-Y, Stern DF. ErbB4 signaling in the mammary gland is required for lobuloalveolar development and Stat5 activation during lactation. J CellBiol 1999;147:77–88.

    CAS  Google Scholar 

  23. Nieman C, Brinkman V, Spitzer E, 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;143:533–545.

    Article  Google Scholar 

  24. Walker RA, Dearing SJ. Expression of epidermal growth factor receptor mRNA and protein in primary breast carcinomas. Breast Cancer Res Treat 1999;53:167–176.

    Article  PubMed  CAS  Google Scholar 

  25. Klijn JG, Berns PM, Schmitz PI, et al. The clinical significance of epidermal growth factor receptor (EGF-R) in human breast cancer: areview on 5232 patients. Endocrinol Rev 1992;13:3–17.

    Article  CAS  Google Scholar 

  26. Chan KC, Gandhi A, Slamon DJ, et al. ProcAmAssoc Cancer Res 2000;41:482 (Abstr 3074).

    Google Scholar 

  27. Earp HS, Dawson TL, Li X, et al. Heterodimerization and functional interaction between EGF receptor family members: a new signaling paradigm with implications for breast cancer research. Breast Cancer Res Treat 1995;35:115–132.

    Article  PubMed  CAS  Google Scholar 

  28. Slamon DJ, Clark GM, Wong SG, et al. Human breast cancer: correlation of relapse and survival with amplification of the HER-2/neu oncogene. Science 1987;235:177–182.

    Article  PubMed  CAS  Google Scholar 

  29. Slamon DJ, Godolphin W, Jones LA, et al. Studies of the HER-2/neu proto-oncogene in human breast and ovarian cancer. Science 1989;244:707–712.

    Article  PubMed  CAS  Google Scholar 

  30. Seshadri R, Firgaira FA, Horsfall DJ, et al. Clinical significance of HER-2/neu oncogene amplification in primary breast cancer. The South Australian Breast Cancer Study Group. J Clin Oncol 1993;11:1936–1942.

    PubMed  CAS  Google Scholar 

  31. Hynes NE, Sterm DF. The biology of erbB2/neu/HER-2 and its role in cancer. Biochem Biophys Acta Rev Cancer 1994;1198:165–184.

    Google Scholar 

  32. Van de Vijver MJ, Peterse JL, et al. Neu-protein overexpression in breast cancer: association with comedo-type ductal carcinoma in situ and limited prognostic value in stage II breast cancer. N Engl J Med 1988;319:1239–1245.

    Article  PubMed  Google Scholar 

  33. Gullick WJ. The c-erbB3/HER3 receptor in human cancer. Cancer Surv 1996;27:339–349.

    PubMed  CAS  Google Scholar 

  34. Srinivasan R, Poulsom R, Hurst H, Gullick W. Expression of the c-erbB-4/HER4 protein and mRNA in normal human fetal and adult tissues and in a survey of nine solid tumour types. J Pathol 1997;185:236–245.

    Article  Google Scholar 

  35. Vogt U, Bielawski K, et al. Amplification of erbB-4 oncogene occurs less frequently than of erbB-2 in primary human breast cancer. Gene 1998;223:375–380.

    Article  PubMed  CAS  Google Scholar 

  36. Bacus SS, Chin D, Zelninick CR, et al. Type 1 receptor tyrosine kinases are differentially phosphorylated in mammary carcinoma and differentially associated with steroid receptors. Am J Pathol 1996;148:549–558.

    PubMed  CAS  Google Scholar 

  37. Knowlden J, Gee J, Seery L, et al. c-erbB-3 and c-erbB-4 expression is a feature of the endocrine responsive phenotype in clinical breast cancer. Oncogene 1998;17:1949–1957.

    Article  PubMed  CAS  Google Scholar 

  38. Mendelsohn J. The epidermal growth factor receptor as target for cancer therapy. Endocr Relat Cancer 2001;8:3–9.

    Article  PubMed  CAS  Google Scholar 

  39. Baselga J, Tripathy D, Mendelsohn J, et al. Phase II study of weekly intravenous recombinant humanized anti-p185HER2 monoclonal antibody in patients with HER2/neu-overexpressing metastatic breast cancer. J Clin Oncol 1996;14:737–744.

    PubMed  CAS  Google Scholar 

  40. Cobleigh MA, Vogel CL, Tripathy D, et al. Multinational study of the efficacy and safety of humanized anti-HER2 monoclonal antibody in women who have HER2-overexpressing metastatic breast cancer that has progressed after chemotherapy for metastatic breast disease. J Clin Oncol 1999;17:2639–2648.

    PubMed  CAS  Google Scholar 

  41. Slamon DJ, Leyland-Jones B, Shak S, et al. Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2. N Engl J Med 2001;344:783–792.

    Article  PubMed  CAS  Google Scholar 

  42. Ernest VL, Barclay J, Kerlikowske K, et al. Incidence of and treatment for ductal carcinoma in situ of the breast. JAMA 1996;275:913–918.

    Article  Google Scholar 

  43. Price P, Sinnett HD, Gusterson B, et al. Ductal carcinomain situ: predictors of local recurrence and progression in patients treated by surgery alone. Br J Cancer 1990;61:869–872.

    PubMed  CAS  Google Scholar 

  44. Silverstein MJ. Ductal carcinoma in situ of the breast. Br Med J 1998;317:734–739.

    CAS  Google Scholar 

  45. Leal CB, Schmitt FC, Bento M. Ductal carcinoma in situ of the breast: histological categorisation and its relationship to ploidy and immunohistochemical expression of hormone receptors, p53, and c-erbB-2 protein. Cancer 1995;75:2123–2128.

    Article  PubMed  CAS  Google Scholar 

  46. Chan KC, Knox WF, Ghandhi A, Slamon DJ, et al. Blockade of growth factor receptors in ductal carcinoma in situ inhibits epithelial proliferation. Br J Surg 2001;88:412–418.

    Article  PubMed  CAS  Google Scholar 

  47. Dent P, Reardon DB, Park JS, et al. Radiation-induced release of transforming growth factor alpha activates the epidermal growth factor receptor and mitogen-activated protein kinase pathway in carcinoma cells, leading to increased proliferation and protection from radiation-induced cell death. Mol Biol Cell 1999;10:2493–2506.

    PubMed  CAS  Google Scholar 

  48. Schmidt-Ullrich RK, Mikkelsen RB, Dent P, et al. Radiation-induced proliferation of the human A431 squamous carcinoma cells is dependent on EGFR tyrosine phosphorylation. Oncogene 1997;15:1191–1197.

    Article  PubMed  CAS  Google Scholar 

  49. Dickstein BM, Wosikowski K, Bate SE. Increased resistance to cytotoxic agents in ZR75B human breast cancer cells transfected with epidermal growth factor receptor. Mol Cell Endocrinol 1995;110:205–211.

    Article  PubMed  CAS  Google Scholar 

  50. Newby JC, Johnston SR, Smith IE, et al. Expression of epidermal growth factor receptor and c-erbB2 during the development of tamoxifen resistance in human breast cancer. Clin Cancer Res 1997;3:1634–1651.

    Google Scholar 

  51. Wright C, Nicholson S, Angus B, et al. Relationship between c-erbB-2 protein product expression and response to endocrine therapy in advanced breast cancer. Br J Cancer 1992;65:118–121.

    PubMed  CAS  Google Scholar 

  52. Fox SB, Harris AL. The epidermal growth factor receptor in breast cancer. J Mammary Gland Biol Neoplasia 1997;2:131–141.

    Article  PubMed  CAS  Google Scholar 

  53. Wosikowski K, Schuurhuis D, Kops GJ, et al. Altered gene expression in drug-resistant human breast cancer cells. Clin Cancer Res 1997;3:2405–2414.

    PubMed  CAS  Google Scholar 

  54. Schmidt-Ullrich RK, Lammering J, Contessa K, et al. Presented at the 11th NCI-EORTC-AACR Symposium on New Drug in Cancer Therapy, Amsterdam, The Netherlands, 2000, Abstr 40.

    Google Scholar 

  55. Mendelsohn J, Fan, Z. Epidermal growth factor receptor family and chemo-sensitization. J Natl Cancer Inst 1997;89:341–343.

    Article  PubMed  CAS  Google Scholar 

  56. Ryan PD, Chabner BA. On receptor inhibitors and chemotherapy. Clin Cancer Res 2000;6:4607–4609.

    PubMed  CAS  Google Scholar 

  57. Bonner J, Robert F, Raisch K, et al. Presented at the 1 1th NCI-EORTC-AACR Symposium on New Drug in Cancer Therapy, Amsterdam, The Netherlands, 2000, Abstr 38.

    Google Scholar 

  58. Nicholson RI, Manning DL, et al. New anti-hormonal approaches to breast cancer therapy. Drugs Today 1993;29:363–372.

    Google Scholar 

  59. Nicholson RI, McClelland RA, Gee JM, et al. Epidermal growth factor receptor expression in breast cancer: association with response to endocrine therapy. Breast Cancer Res Treat 1994;29:117–125.

    Article  PubMed  CAS  Google Scholar 

  60. Nicholson RI, Gee JMW, Harper ME, et al. ErbB signalling in clinical breast cancer: relationship to endocrine sensitivity. Endocr Relat Cancer 1997;4:1–9.

    Article  Google Scholar 

  61. Nicholson RI, Gee JMW, Jones H, et al. ErbB signalling in clinical breast cancer. In: Ernst Schering Research Foundation Workshop 19: EGF Receptor in Tumour Growth and Progression, 1997, pp. 105–128.

    Google Scholar 

  62. Elledge RM, Green S, Ciocca D, et al. HER-2 expression and response to tamoxifen in estrogen receptor-positive breast cancer: a Southwest Oncology Group Study. Clin Cancer Res 1998;4:7–12.

    PubMed  CAS  Google Scholar 

  63. Houston SJ, Plunkett TA, Barnes DM, et al. Over-expression of c-erbB2 is a independent marker of resistance to endocrine therapy in advanced breast cancer. BrJ Cancer 1999;79:1220–1226.

    Article  CAS  Google Scholar 

  64. Bates SE, Davidson NE, Valverius EM, et al. Expression of transforming growth factor alpha and its messenger ribonucleic acid in human breast cancer: its regulation by estrogen and ist possible functional significance. Mol Endocrinol 1988;2:543–555.

    PubMed  CAS  Google Scholar 

  65. Lee AV, Darbre P, King RJ. Processing of insulin like growth factor-II (IGF-II) by human breast cancer cells. Mol Cell Endocrinol 1994;99:211–220.

    Article  PubMed  CAS  Google Scholar 

  66. Aronica SM, Katzenellenbogen BS. Stimulation of estrogen receptor-mediated transcription and alteration in the phosphorylation state of rat uterine estrogen receptor by estrogen, cyclic adenosinemonophosphate, and insulin-like growth factor-I. Mol Endocrinol 1993;7:743–752.

    Article  PubMed  CAS  Google Scholar 

  67. Bunone G, Briand PA, Miksicek RJ, Picard D. Activation of the unliganded estrogen receptor by EGF involves the MAP kinase pathway and direct phosphorylation. EMBO J 1996;15:2174–2183.

    PubMed  CAS  Google Scholar 

  68. Richards RG, DiAugustine RP, Petrusz P, Clark GC, Sebastian J. Estradiol stimulates tyrosine phosphorylation of the insulin-like growth factor-1 receptor and insulin receptor substrate-1 in the uterus. PNAS 1996;93:12002–12007.

    Article  PubMed  CAS  Google Scholar 

  69. Freiss G, Rochefort H, Vignon F. Mechanisms of 4-hydroxytamoxifen anti-growth factor receptor binding sites and tyrosine kinase activity. Biochem Biophy Res Commun 1990;31:919–926.

    Article  Google Scholar 

  70. Guvakova MA, Surmacz E. Tamoxifen interferes with the insulin-like growth factor I receptor (IGF-IR) signaling pathway in breast cancer cells. Cancer Res 1997;57:2606–2610.

    PubMed  CAS  Google Scholar 

  71. Dati C, Antoniotti S, Taverna D, Perroteau I, De Bortoli M. Inhibition of c-erbB2 oncogene expression by oestrogens in human breast cancer cells. Oncogene 1990;5:1001–1006.

    PubMed  CAS  Google Scholar 

  72. Chrysogelos SA, Yarden RI, Lauber AH, Murphy JM. Mechanisms of EGF receptor regulation in breast cancer cells. Breast Cancer Res Treat 1994;31:227–236.

    Article  PubMed  CAS  Google Scholar 

  73. Yarden RI, Lauber AH, EI-Ashry D, Chrysogelos SA. Bimodal regulation of epidermal growth factorreceptor by estrogen in breast cancer cells. Endocrinology 1996;137:2739–2747.

    Article  PubMed  CAS  Google Scholar 

  74. De Fazio A, Chiew Ye, McEvoy M, Watts CK, Sutherland RL. Antisense estrogen receptor RNA expression increases epidermal growth factor receptor gene expression in breast cancer cells. Cell Growth Differ 1997;8:903–911.

    Google Scholar 

  75. Cheung KL, Willsher PC, Pinder SE, et al. Predictors of response to second-line endocrine therapy for breast cancer. Breast Cancer Res Treat 1997;45:219–224.

    Article  PubMed  CAS  Google Scholar 

  76. McClelland RA, Barrow D, Madden TA, et al. Enhanced epidermal growth factor receptor signalling in MCF-7 breast cancer cells after long-term culture in the presence of the pure antioestrogen ICI 182,780 (faslodex). Endocrinology 2001;142:2776–2788.

    Article  PubMed  CAS  Google Scholar 

  77. Salomon DS, Brandt R, Ciardiello F, Normanno N. Epidermal growth factor-related peptides and their receptors in human malignancies. Crit Rev Oncol Hematol 1995;19:183–232.

    Article  PubMed  CAS  Google Scholar 

  78. Slamon DJ, Clark GM, Wong SG, et al. Human breast cancer: correlation of relapse and survival with amplification of the HER-2/neu oncogene. Science 1987;235:177–182.

    Article  PubMed  CAS  Google Scholar 

  79. Harris AL, Nicholoson S, Sainsbury JR, et al. Epidermal growth factor receptor: a marker of early relapse in breast cancer and tumour stage progression in bladder cancer; interactions with neu. In: Furth M, Greaves M, eds. The Molecular Diagnostics of Human Cancer, Vol. 7: Cancer Cells. Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY, 1989;353–357.

    Google Scholar 

  80. Moasser MM, Basso A, Averbuch SD, Rosen N. The tyrosine kinase inhibitor ZD1839 (Iressa) inhibits HER2-driven signaling and suppresses the growth of HER2-overexpressing tumor cells. Cancer Res 2001;61:7184–7188.

    PubMed  CAS  Google Scholar 

  81. Moulder SL, Yakes M, Muthuswamy SK, Bianco R, Simpson JF, Arteaga C. Epidermal growth factor receptor (HER1) tyrosine kinase inhibitor ZD1839 (Iressa) inhibits HER2/neu (erbB2)-overexpressing breast cancer cells in vitro and in vivo. Cancer Res 2001;61:8887–8895.

    PubMed  CAS  Google Scholar 

  82. Normanno N, Campiglio M, De Luca A, et al. Cooperative inhibitory effect of ZD1839 (IRESSA) in combination with trastuzmab (Herceptin) on human breast cancer cell growth. Ann Oncol 2002;13:65–72.

    Article  PubMed  CAS  Google Scholar 

  83. Anido J, Albanell J, Rojo F, Guzman M, et al. ZD1839, a specific epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, induces the formation of inactive EGFR/HER2 and EGFR/HER3 heterodimers and prevents heregulin signaling in HER2-overexpressing breast cancer cells. Clin Cancer Res 2003;9:1274–1283.

    PubMed  CAS  Google Scholar 

  84. Normanno N, Maiello MR, De Luca A. Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs): simple drugs with a complex mechanism of action? J Cell Physiol 2003;194:13–19.

    Article  PubMed  CAS  Google Scholar 

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Ciardiello, F., Troiani, T., Tortora, G. (2006). The Epidermal Growth Factor Receptor Pathway as a Selective Molecular-Targeted Treatment in Human Breast Cancer. In: Gasparini, G., Hayes, D.F. (eds) Biomarkers in Breast Cancer. Cancer Drug Discovery and Development. Humana Press. https://doi.org/10.1385/1-59259-915-X:177

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