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Toward Checkmate: Biology and Breast Cancer Therapy for the New Millennium

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Abstract

A better understanding of the biology of breast cancer should leadto the rational development of new treatments and the ability tocustomize therapy for individual patients. Though promising intheory, translating advances in biological knowledge to the clinichas been difficult. Recently several areas of research haveproduced treatments which have entered clinical trials; three willbe reviewed here. The growth of breast cancer is regulated bygrowth factors and their receptors; amplification or overexpressionis associated with poor prognosis. As such inhibition of growthfactors and/or growth factor receptors may provide an idealtherapeutic target. Herceptin binds to c-erbB-2, a member of theepidermal growth factor receptor family. Significant responses wereseen in patients with c-erbB-2 overexpressing breast cancer withHerceptin administered as a single agent or in combination withchemotherapy. Herceptin was approved by the Food and DrugAdministration in late 1998. Breast cancer invasion and metastasisrequires degradation of the surrounding basement membrane by matrixmetalloproteinases and other proteolytic enzymes. Syntheticinhibitors of these enzymes are now in clinical trials. Breastcancers must stimulate angiogenesis, the growth of new bloodvessels, in order to grow beyond a few millimeters in diameter.This nascent vascular network provides another opportunity fortherapy. Preclinical models support the critical role ofangiogenesis and the therapeutic benefit of angiogenesisinhibition; clinical trials are underway.

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References

  1. Beaston G: On the treatment of inoperable cases of carcinoma of the mamma: Suggestions for a new method of treatment, with illustrative cases. Lancet 2: 104–107, 1896

    Google Scholar 

  2. Jensen E, DeSombre E, Jungblut P: Estrogen receptors in hormone responsive tissues and tumors. Chicago, University of Chicago Press, 1969

    Google Scholar 

  3. Kupier G, Enmark E, Pelto-Huikko M et al.: Cloning of a novel estrogen receptor expressed in rat prostate and ovary. Proc Natl Acad Sci USA 93: 5925–5930, 1996

    Google Scholar 

  4. Mosselman S, Polman J, Dijkema R: ER beta: identification and characterization of a novel human estrogen receptor. FEBS Lett 392: 49–53, 1996

    Google Scholar 

  5. Kuiper GG, Carlsson B, Grandien K et al.: Comparison of the ligand binding specificity and transcript tissue distribution of estrogen receptors alpha and beta. Endocrinology 138: 863–870, 1997

    Google Scholar 

  6. Kuiper GG, Lemmen JG, Carlsson B et al.: Interaction of estrogenic chemicals and phytoestrogens with estrogen receptor beta. Endocrinology 139: 4252–4263, 1998

    Google Scholar 

  7. Paech K, Webb P, Kuiper GG et al.: Differential ligand activation of estrogen receptors ERalpha and ERbeta at AP1 sites [see comments]. Science 277: 1508–1510, 1997

    Google Scholar 

  8. Clark GM, Osborne CK, McGuire WL: Correlations between estrogen receptor, progesterone receptor, and patient characteristics in human breast cancer. J Clin Oncol 2: 1102–1109, 1984

    Google Scholar 

  9. Jordan VC: The strategic use of antiestrogens to control the development and growth of breast cancer. Cancer 70: 977–982, 1992

    Google Scholar 

  10. Jackson TA, Richer JK, Bain DL et al.: The partial agonist activity of antagonist-occupied steroid receptors is controlled by a novel hinge domain-binding coactivator L7/SPA and the corepressors N-Cor or SMRT. Mol Endocrinol 11: 693–705, 1997

    Google Scholar 

  11. Gradishar WJ, Jordan VC: Clinical potential of new antiestrogens. J Clin Oncol 15: 840–852, 1997

    Google Scholar 

  12. Nakshatri H, Bhat-Nakshatri P, Martin DA et al.: Constitutive activation of NF-kappaB during progression of breast cancer to hormone-independent growth. Mol Cell Biol 17: 3629–3639, 1997

    Google Scholar 

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

    Google Scholar 

  14. Devilee P, Cornelisse CJ: Somatic genetic changes in human breast cancer. Biochem Biophys Acta 1198: 113–130, 1994

    Google Scholar 

  15. 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 235: 177–182, 1987

    Google Scholar 

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

    Google Scholar 

  17. Winstanley J, Cooke T, George WD et al.: The long-term prognostic significance of oestrogen receptor analysis in early carcinoma of the breast. Br J Cancer 64: 99–101, 1991

    Google Scholar 

  18. Paterson MC, Dietrich KD, Danyluk J et al.: Correlation between c-erbB-2 amplification and risk of recurrent disease in node-negative breast cancer. Cancer Res 51: 556–567, 1991

    Google Scholar 

  19. Berns EM, Klijn JG, van Putten WL et al.: c-myc amplification is a better prognostic factor than HER2/neu amplification in primary breast cancer. Cancer Res 52: 1107–1113, 1992

    Google Scholar 

  20. Clark GM, McGuire WL: Follow-up study of HER-2/neu amplification in primary breast cancer. Cancer Res 51: 944–948, 1991

    Google Scholar 

  21. Press MF, Bernstein L, Thomas PA et al.: HER-2/neu gene amplification characterized by fluorescence in situhybridization: poor prognosis in node-negative breast carcinomas. J Clin Oncol 15: 2894–2904, 1997

    Google Scholar 

  22. Stender M, Neuberg D, Wood W et al.: Correlation of circulating c-erb B-2 extracellular domain with clinical outcome in patients with metastatic breast cancer. Proc Am Soc Clin Oncol 16: 154a, 1997

    Google Scholar 

  23. Revillion F, Bonneterre J, Peyrat JP: ERBB2 oncogene in human breast cancer and its clinical significance. Eur J Cancer 34: 791–808, 1998

    Google Scholar 

  24. Gusterson BA, Gelber RD, Goldhirsch A et al.: Prognostic importance of c-erbB-2 expression in breast cancer. International (Ludwig) Breast Cancer Study Group [see comments]. J Clin Oncol 10: 1049–1056, 1992

    Google Scholar 

  25. Allred DC, Clark GM, Tandon AK et al.: HER-2/neu in node-negative breast cancer: prognostic significance of over424 expression influenced by the presence of in situcarcinoma. J Clin Oncol 10: 599–605, 1992

    Google Scholar 

  26. Ravdin P, Green S, Albain K et al.: Initial report of the SWOG biological correlative study of c-erbB-2 expression as a predictor of outcome in a trial comparing adjuvant CAFT with Tamoxifen alone. Proc Am Soc Clin Oncol 17: 97a, 1998

    Google Scholar 

  27. Thor AD, Berry DA, Budman DR et al.: erbB-2.p53, and efficacy of adjuvant therapy in lymph node-positive breast cancer [see comments]. J Natl Cancer Inst 90: 1346–1360, 1998

    Google Scholar 

  28. Paik S, Bryant J, Park C et al.: erbB-2 and response to doxorubicin in patients with axillary lymph node-positive, hormone receptor-negative breast cancer [see comments]. J Natl Cancer Inst 90: 1361–1370, 1998

    Google Scholar 

  29. Yang L, Loicheva V, Colvin O et al.: Different response to adriamycin vs. cytoxan-based chemotherapy in ERBB2 positive breast cancer is associated with alteration in topoisomerase IIalpha expression. Breast Cancer Res Treat 50: 231, 1998

    Google Scholar 

  30. Bianco A, De Laurentis M, Carlomagno C et al.: 20 year update of the Naples GUN trial of adjuvant breast cancer therapy: evidence of the interaction between c-erb-B2 expression and tamoxifen efficacy. Proc Am Soc Clin Oncol 17: 97a, 1998

    Google Scholar 

  31. 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 4: 7–12, 1998

    Google Scholar 

  32. Kumar R, Mandal M, Lipton A et al.: Overexpression of HER2 modulates bcl-2, bcl-XL, and tamoxifen-induced apoptosis in human MCF-7 breast cancer cells. Clin Cancer Res 2: 1215–1219, 1996

    Google Scholar 

  33. Drebin J, Link V, Greene M: Monoclonal antibodies specific for the Neu oncogene product directly mediate anti-tumor effects in vivo. Oncogene 2: 387–394, 1988

    Google Scholar 

  34. Cobleigh M, Cogel C, Tripathy N et al.: Efficacy and safety of Herceptin (humanized anti-Her2 antibody) as a single agent in 222 women with Her2 overexpression who relapsed following chemotherapy for metastatic breast cancer. Proc Am Soc Clin Oncol 17: 97, 1998

    Google Scholar 

  35. Slamon D, Leyland-Jones B, Shak S et al.: Addition of Herceptin (humanized anti-Her2 antibody) to first line chemotherapy for Her2 overexpressing metastatic breast cancer markedly increases anticancer activity: A randomized, multinational controlled phase III trial. Proc Am Soc Clin Oncol 17: 98, 1998

    Google Scholar 

  36. Fitzgerald D, Pastan I: Targeted toxin therapy for the treatment of cancer. J Natl Cancer Inst 81: 1455–1463, 1989

    Google Scholar 

  37. Arteaga C, Hurd S, Dugger T et al.: Epidermal growth factor receptors in human breast carcinoma cells: a potential selective target for transforming growth factor alpha-Pseudomonas exotoxin 40 fushion protein. Cancer Res 54: 4703–4709, 1994

    Google Scholar 

  38. Valone F, Kaufman P, Guyre P et al.: Phase Ia/Ib trial of bispecific antibody MDX-210 in patients with advanced breast or ovarian cancer that overexpress the proto-oncogene HER-2/neu. J Clin Oncol 13: 2281–2292, 1995

    Google Scholar 

  39. Zhang L, Chang C, Bacus S et al.: Suppressed transformation and induced differentiation of HER-2/neu-overexpressing breast cancer cell by emodin. Cancer Res 55: 3890–3896, 1995

    Google Scholar 

  40. Levitski A, Gazit A: Tyrosine kinase inhibition: an approach to drug development. Science 267: 1782–1787, 1995

    Google Scholar 

  41. Baserga R: IGF-1 receptor as the restriction point of the cell cycle. Ann NY Acad Sci 663: 154–157, 1992

    Google Scholar 

  42. Westley B, May F: Insulin-like growth factors: the unrecognized oncogenes. Br J Cancer 72: 1065–1066, 1995

    Google Scholar 

  43. Ingle J, Kardinal C, Suman V et al.: Randomized trial of tamoxifen alone or combinated with octreotide in women with metastatic breast cancer. Proc Am Soc Clin Oncol 16: 526, 1997

    Google Scholar 

  44. Favoni RE, de Cupis A, Bruno S et al.: Modulation of the insulin-like growth factor-I system by N-(4-hydroxyphenyl)-retinamide in human breast cancer cell lines. Br J Cancer 77: 2138–2147, 1998

    Google Scholar 

  45. Toma S, Isnardi L, Riccardi L et al.: Induction of apoptosis in MCF-7 breast carcinoma cell line by RAR and RXR selective retinoids. Anticancer Res 18: 935–942, 1998

    Google Scholar 

  46. Grunt ThW, Dittrich E, Offterdinger Met al.: Effects of retinoic acid and fenretinide on the c-erbB-2 expression, growth and cisplatin sensitivity of breast cancer cells. Br J Cancer 78: 79–87, 1998

    Google Scholar 

  47. Cobleigh MA, Dowlatshahi K, Deutsch TA et al.: Phase I/II trial of tamoxifen with or without fenretinide, an analog of vitamin A, in women with metastatic breast cancer. J Clin Oncol 11: 474–477, 1993

    Google Scholar 

  48. Gottardis MM, Bischoff ED, Shirley MA et al.: Chemoprevention of mammary carcinoma by LGD 1069 (Targretin): an RXR-selective ligand. Cancer Res 56: 5566–5570, 1996

    Google Scholar 

  49. Bischoff ED, Gottardis MM, Moon TE et al.: Beyond tamoxifen: the retinoid X receptor-selective ligand LGD1069 (TARGRETIN) causes complete regression of mammary carcinoma. Cancer Res 58: 479–484, 1998

    Google Scholar 

  50. Folkman J:What is the evidence that tumors are angiogenesis dependent? J Natl Cancer Inst 82: 4–6, 1990

    Google Scholar 

  51. Pepper MS, Mandriota SJ, Vassalli JD et al.: Angiogenesisregulating cytokines: activities and interactions. Curr Top Microbiol Immunol 213: 31–67, 1996

    Google Scholar 

  52. Jensen HM, Chen I, DeVault MR et al.: Angiogenesis induced by "normal" human breast tissue: a probable marker for precancer. Science 218: 293–295, 1982

    Google Scholar 

  53. Brem SS, Gullino PM, Medina D: Angiogenesis: a marker for neoplastic transformation of mammary papillary hyperplasia. Science 195: 880–882, 1977

    Google Scholar 

  54. Monteagudo C, Merino MJ, San-Juan J et al.: Immunohistochemical distribution of type IV collagenase in normal, benign, and malignant breast tissue. Am J Pathol 136: 585–592, 1990

    Google Scholar 

  55. Kossakowska AE, Muchcroft SA, Urbanski SJ et al.: Comparative analysis of the expression patterns of metalloproteinases and their inhibitors in breast neoplasia, sporadic colorectal neoplasia, pulmonary carcinomas and malignant non-Hodgkin's lymphomas in humans. Br J Cancer 73: 1401–1408, 1996

    Google Scholar 

  56. Folkman J, Hanahan D: Switch to the angiogenic phenotype during tumorigenesis. Princess Takamatsu Symp 22: 339–347, 1991

    Google Scholar 

  57. Holmgren L, O'Reilly MS, Folkman J: Dormancy of micrometastases: balanced proliferation and apoptosis in the presence of angiogenesis suppression [see comments]. Nat Med 1: 149–153, 1995

    Google Scholar 

  58. Azzam HS, Arand G, Lippman ME et al.: Association of MMP-2 activation potential with metastatic progression in human cancer cell lines independent of MMP-2 production. J Natl Cancer Inst 85: 1758–1764, 1993

    Google Scholar 

  59. Kurebayashi J, McLeskey SW, Johnson MD et al.: Quantitative demonstration of spontaneous metastasis by MCF-7 hu425 man breast cancer cells cotransfected with fibroblast growth factor 4 and LacZ. Cancer Res 53: 2178–2187, 1993

    Google Scholar 

  60. Zhang HT, Craft P, Scott PA et al.: Enhancement of tumor growth and vascular density by transfection of vascular endothelial cell growth factor into MCF-7 human breast carcinoma cells. J Natl Cancer Inst 87: 213–219, 1995

    Google Scholar 

  61. Giunciuglio D, Culty M, Fassina G et al.: Invasive phenotype of MCF10A cells overexpression c-Ha-ras and c-erbB-2 oncogenes. Int J Cancer 63: 815–822, 1995

    Google Scholar 

  62. Nakajima M, Welch DR, Belloni PN et al.: Degradation of basement membrane type IV collagen and lung subendothelial matrix by rat mammary adenocarcinoma cell clones of differing metastatic potentials. Cancer Res 47: 4869–4876, 1987

    Google Scholar 

  63. Nakajima M, Welch DR, Wynn DMet al.: Serum and plasma M(r) 92,000 progelatinase levels correlate with spontaneous metastasis of rat 13762NF mammary adenocarcinoma. Cancer Res 53: 5802–5807, 1993

    Google Scholar 

  64. Liotta LA, Steeg PS, Stetler-Stevenson WG: Cancer metastasis and angiogenesis: an imbalance of positive and negative regulation. Cell 64: 327–336, 1991

    Google Scholar 

  65. Weinstat-Saslow DL, Zabrenetzky VS, VanHoutte K et al.: Transfection of thrombospondin 1 complementary DNA into a human breast carcinoma cell line reduces primary tumor growth, metastatic potential, and angiogenesis. Cancer Res 54: 65-4–6511, 1994

    Google Scholar 

  66. Wang M, Liu YE, Greene J et al.: Inhibition of tumor growth and metastasis of human breast cancer cells transfected with tissue inhibitor of metalloproteinase 4. Oncogene 14: 2767–2774, 1997

    Google Scholar 

  67. Eppenberger U, Kueng W, Schlaeppi JMet al.:Markers of tumor angiogenesis and proteolysis independently define highand low-risk subsets of node-negative breast cancer patients. J Clin Oncol 16: 3129–3136, 1998

    Google Scholar 

  68. Gasparini G, Toi M, Gion M et al.: Prognostic significance of vascular endothelial growth factor protein in node-negative breast carcinoma. J Natl Cancer Inst 89: 139–147, 1997

    Google Scholar 

  69. Gasparini G, Brooks PC, Biganzoli E et al.: Vascular integrin alpha(v)beta(3): a new prognostic indicator in breast cancer [In Process Citation]. Clin Cancer Res 4: 2625–2634, 1998

    Google Scholar 

  70. Linderholm B, Tavelin B, Grankvist K et al.: Vascular endothelial growth factor is of high prognostic value in nodenegative breast carcinoma. J Clin Oncol 16: 3121–3128, 1998

    Google Scholar 

  71. Relf M, LeJeune S, Scott PA et al.: Expression of the angiogenic factors vascular endothelial cell growth factor, acidic and basic fibroblast growth factor, tumor growth factor beta-1, platelet-derived endothelial cell growth factor, placenta growth factor, and pleiotrophin in human primary breast cancer and its relation to angiogenesis. Cancer Res 57: 963–967, 1997

    Google Scholar 

  72. Toi M, Hoshina S, Takayanagi T et al.: Association of vascular endothelial growth factor expression with tumor angiogenesis and with early relapse in primary breast cancer. Jpn J Cancer Res 85: 1045–1049, 1994

    Google Scholar 

  73. Daidone MG, Silvestrini R, D'Errico A et al.: Laminin receptors, collagenase IV and prognosis in node-negative breast cancers. Int J Cancer 48: 529–532, 1991

    Google Scholar 

  74. Zajchowski DA, Band V, Trask DK et al.: Suppression of tumor-forming ability and related traits in MCF-7 human breast cancer cells by fusion with immortal mammary epithelial cells. Proc Natl Acad Sci USA 87: 2314–2318, 1990

    Google Scholar 

  75. Weidner N, Semple J, Welch W et al.: Tumor angiogenesis and metastasis – correlation in invasive breast cancer. N Engl J Med 324: 1–8, 1991

    Google Scholar 

  76. Toi M, Inada K, Suzuki H et al.: Tumor angiogenesis in breast cancer: its importance as a prognostic indicator and the association with vascular endothelial growth factor expression. Breast Cancer Res Treat 36: 193–204, 1995

    Google Scholar 

  77. Bevilacqua P, Barbareschi M, Verderio P et al.: Prognostic value of intratumoral microvessel density, a measure of tumor angiogenesis, in node-negative breast carcinoma – results of a multiparametric study. Breast Cancer Res Treat 36: 205–217, 1995

    Google Scholar 

  78. Hall N, Fish D, Hunt N et al.: Is the relationship between angiogenesis and metastasis in breast cancer real? Surg Oncol 1: 223–229, 1992

    Google Scholar 

  79. Van Hoef M, Knox W, Dhesi S et al.: Assessment of tumor vascularity as a prognostic factor in lymph node negative invasive breast cancer. Eur J Cancer 29A: 1141–1145, 1993

    Google Scholar 

  80. Vermeulen PB, Libura M, Libura J et al.: Influence of investigator experience and microscopic field size on microvessel density in node-negative breast carcinoma. Breast Cancer Res Treat 42: 165–172, 1997

    Google Scholar 

  81. Vermeulen PB, Gasparini G, Fox SB et al.: Quantification of angiogenesis in solid human tumours: an international consensus on the methodology and criteria of evaluation. Eur J Cancer 32A: 2474–2484, 1996

    Google Scholar 

  82. Weidner N: Current pathologic methods for measuring intratumoral microvessel density within breast carcinoma and other solid tumors. Breast Cancer Treat Res 36: 169–180, 1995

    Google Scholar 

  83. McCulloch P, Choy A, Martin L: Association between tumour angiogenesis and tumour cell shedding into effluent venous blood during breast cancer surgery [see comments]. Lancet 346: 1334–1335, 1995

    Google Scholar 

  84. Fox S, Leek R, Bliss J et al.: Association of tumor angiogenesis with bone marrow micrometastases in breast cancer patients. J Natl Cancer Inst 89: 1044–1049, 1997

    Google Scholar 

  85. Brooks PC, Silletti S, von Schalscha TL et al.: Disruption of angiogenesis by PEX, a noncatalytic metalloproteinase fragment with integrin binding activity. Cell 92: 391–400, 1998

    Google Scholar 

  86. Fisher C, Gilbertson-Beadling S, Powers EA et al.: Interstitial collagenase is required for angiogenesis in vitro. DevBiol 162: 499–510, 1994

    Google Scholar 

  87. Low JA, Johnson MD, Bone EA et al.: The matrix metalloproteinase inhibitor batimastat (BB-94) retards human breast cancer solid tumor growth but not ascites formation in nude mice. Clin Cancer Res 2: 2107–1214, 1996

    Google Scholar 

  88. Kurizaki T, Toi M, Tominaga T: Relationship between matrix metalloproteinase expression and tumor angiogenesis in human breast carcinoma. Oncol Rep 5: 673–677, 1998

    Google Scholar 

  89. Taraboletti G, Garofalo A, Belotti D et al.: Inhibition of angiogenesis and murine hemangioma growth by batimastat, a synthetic inhibitor of matrix metalloproteinases. J Natl Cancer Inst 87: 293–298, 1995

    Google Scholar 

  90. Tamargo RJ, Bok RA, Brem H: Angiogenesis inhibition by minocycline. Cancer Res 51: 672–675, 1991

    Google Scholar 

  91. Fife RS, Sledge GW Jr.: Effects of doxycycline on in vitrogrowth, migration, and gelatinase activity of breast carcinoma cells. J Lab Clin Med 125: 407–411, 1995

    Google Scholar 

  92. Gordon M, Battiato L, Jones D et al.: A phase I trial of doxocycline in patients with cancer. Proc Am Soc Clin Oncol 16: 226a, 1997

    Google Scholar 

  93. Sledge GW Jr., Qulali M, Goulet R et al.: Effect of matrix metalloproteinase inhibitor batimastat on breast cancer regrowth and metastasis in athymic mice. J Natl Cancer Inst 87: 1546–1550, 1995

    Google Scholar 

  94. Sledge G, Qulali M, Bone E et al.: Combination matrix metalloproteinase inhibition in an athymic mouse xenograft model of human breast cancer metastasis. Proc Am Assoc Cancer Res 37: A639, 1996

    Google Scholar 

  95. Wojtowicz-Praga S, Torri J, Johnson M et al.: Phase I trial of Marimastat, a novel matrix metalloproteinase inhibitor, administered orally to patients with advanced lung cancer. J Clin Oncol 16: 2150-2165, 1998

    Google Scholar 

  96. Yunmbam MK: Inhibition of breast cancer in nude mouse model by anti-angiogenesis. Oncol Rep 5: 1431-1437, 1998

    Google Scholar 

  97. Zugmaier G, Lippman ME, Wellstein A: Inhibition by pentosan polysulfate (PPS) of heparin-binding growth factors released from tumor cells and blockage by PPS of tumor growth in animals. J Natl Cancer Inst 84: 1716–1724, 1992

    Google Scholar 

  98. Lindman H, Taube A, Bergh JC: Suramin inhibits the growth of human breast cancer cell lines. Studies on parental lines and corresponding sublines with acquired doxorubicin resistance with and without expression of P-glycoprotein. Anticancer Res 14: 363–366, 1994

    Google Scholar 

  99. Lawrence JB, Conover CA, Haddad TC et al.: Evaluation of continuous infusion suramin in metastatic breast cancer: impact on plasma levels of insulin-like growth factors (IGFs) and IGF-binding proteins [In Process Citation]. Clin Cancer Res 3: 1713–1720, 1997

    Google Scholar 

  100. Boylan M, van den Berg HW, Lynch M: The antiproliferative effect of suramin towards tamoxifen-sensitive and resistant human breast cancer cell lines in relation to expression of receptors for epidermal growth factor and insulinlike growth factor-I: growth stimulation in the presence of tamoxifen. Ann Oncol 9: 205–211, 1998

    Google Scholar 

  101. Warren RS, Yuan H, Matli MR et al.: Regulation by vascular endothelial growth factor of human colon cancer tumorigenesis in a mouse model of experimental liver metastasis. J Clin Invest 95: 1789–1797, 1995

    Google Scholar 

  102. Kim KJ, Li B, Winer J et al.: Inhibition of vascular endothelial growth factor-induced angiogenesis suppresses tumour growth in vivo. Nature 362: 841–844, 1993

    Google Scholar 

  103. Gordon M, Talpaz M, Margolin K et al.: Phase I trial of recombinant humanized monoclonal anti-vascular endothelial growth factor (anti-VEGF Mab) in patients with metastatic cancer. Proc Am Soc Clin Oncol 17: 210a, 1998

    Google Scholar 

  104. Millauer B, Longhi MP, Plate KH et al.: Dominant-negative inhibition of Flk-1 suppresses the growth of many tumor types in vivo. Cancer Res 56: 1615–1620, 1996

    Google Scholar 

  105. Fong TA, Shawver LK, Sun L et al.: SU5416 is a potent and selective inhibitor of the vascular endothelial growth factor receptor (Flk-1/KDR) that inhibits tyrosine kinase catalysis, tumor vascularization, and growth of multiple tumor types. Cancer Res 59: 99–106, 1999

    Google Scholar 

  106. Rosen L, Kabbinavar F, Rosen P et al.: Phase I trial of SU5416, a novel angiogenesis inhibitor in patients with advanced malignancies. Proc Am Soc Clin Oncol 17: 218a, 1998

    Google Scholar 

  107. Thorpe PE, Burrows FJ: Antibody-directed targeting of the vasculature of solid tumors [see comments]. Breast Cancer Res Treat 36: 237–251, 1995

    Google Scholar 

  108. Burrows FJ, Derbyshire EJ, Tazzari PL et al.: Up-regulation of endoglin on vascular endothelial cells in human solid tumors: implications for diagnosis and therapy. Clin Cancer Res 1: 1623–1634, 1995

    Google Scholar 

  109. McLeskey SW, Zhang L, Trock BJ et al.: Effects of AGM-1470 and pentosan polysulphate on tumorigenicity and metastasis of FGF-transfected MCF-7 cells. Br J Cancer 73: 1053–1062, 1996

    Google Scholar 

  110. Sasaki A, Alcalde RE, Nishiyama A et al.: Angiogenesis inhibitor TNP-470 inhibits human breast cancer osteolytic bone metastasis in nude mice through the reduction of bone resorption. Cancer Res 58: 462–467, 1998

    Google Scholar 

  111. Singh Y, Shikata N, Kiyozuka Y et al.: Inhibition of tumor growth and metastasis by angiogenesis inhibitor TNP-470 on breast cancer cell lines in vitroand in vivo. Breast Cancer Res Treat 45: 15–27, 1997

    Google Scholar 

  112. Brooks PC, Clark RA, Cheresh DA: Requirement of vascular integrin alpha v beta 3 for angiogenesis. Science 264: 569–571, 1994

    Google Scholar 

  113. Brooks PC, Montgomery AM, Rosenfeld M et al.: Integrin alpha v beta 3 antagonists promote tumor regression by inducing apoptosis of angiogenic blood vessels. Cell 79: 1157–1164, 1994

    Google Scholar 

  114. Brooks PC, Stromblad S, Klemke R et al.: Antiintegrin alpha v beta 3 blocks human breast cancer growth and angiogenesis in human skin [see comments]. J Clin Invest 96: 1815–1822, 1995

    Google Scholar 

  115. Gutheil J, Campbell T, Pierce J et al.: Phase I study of vitaxin, an anti-angiogenic humanized monoclonal antibody to vascular integrin alphav_3. Proc Am Soc Clin Oncol 17: 215a, 1998

    Google Scholar 

  116. Arnoletti JP, Albo D, Granick MS et al.: Thrombospondin and transforming growth factor-beta 1 increase expression of urokinase-type plasminogen activator and plasminogen activator inhibitor-1 in human MDA-MB-231 breast cancer cells. Cancer 76: 998–1005, 1995

    Google Scholar 

  117. Xu M, Kumar D, Stass SA et al.: Gene therapy with p53 and a fragment of thrombospondin I inhibits human breast cancer in vivo. Mol Genet Metab 63: 103–109, 1998

    Google Scholar 

  118. Wang TN, Qian XH, Granick MS et al.: Inhibition of breast cancer progression by an antibody to a thrombospondin-1 receptor. Surgery 120: 449–454, 1996

    Google Scholar 

  119. Guo NH, Krutzsch HC, Inman JK et al.: Antiproliferative and antitumor activities of D-reserve peptides derived from the second type-1 repeat of thrombospondin-1. J Pept Res 50: 210–221, 1997

    Google Scholar 

  120. Silva ID, Salicioni AM, Russo IH et al.: Tamoxifen downregulates CD36 messenger RNA levels in normal and neoplastic human breast tissues. Cancer Res 57: 378–381, 1997

    Google Scholar 

  121. Fisher B, Saffer E, Rudock C et al.: Presence of a growth stimulating factor in serum following primary tumor removal in mice. Cancer Res 49: 1996–2001, 1989

    Google Scholar 

  122. Fisher B, Gunduz N, Saffer EA: Influence of the interval between primary tumor removal and chemotherapy on kinetics and growth of metastases. Cancer Res 43: 1488–1492, 1983

    Google Scholar 

  123. Simpson-Herren L, Sanford AH, Holmquist JP: Effects of surgery on the cell kinetics of residual tumor. Cancer Treat Rep 60: 1749–1760, 1976

    Google Scholar 

  124. O'Reilly MS, Holmgren L, Shing Y et al.: Angiostatin: a novel angiogenesis inhibitor that mediates the suppression of metastases by a Lewis lung carcinoma [see comments]. Cell 79: 315–328, 1994

    Google Scholar 

  125. O'Reilly MS, Holmgren L, Chen C et al.: Angiostatin induces and sustains dormancy of human primary tumors in mice. Nat Med 2: 689–692, 1996

    Google Scholar 

  126. Griscelli F, Li H, Bennaceur-Griscelli A et al.: Angiostatin gene transfer: inhibition of tumor growth in vivoby block427 age of endothelial cell proliferation associated with a mitosis arrest. Proc Natl Acad Sci USA 95: 6367–6372, 1998

    Google Scholar 

  127. Gorski DH, Mauceri HJ, Salloum RM et al.: Potentiation of the antitumor effect of ionizing radiation by brief concomitant exposures to angiostatin. Cancer Res 58: 5686–5689, 1998

    Google Scholar 

  128. O'Reilly MS, Boehm T, Shing Y et al.: Endostatin: an endogenous inhibitor of angiogenesis and tumor growth. Cell 88: 277–285, 1997

    Google Scholar 

  129. Hohenester E, Sasaki T, Olsen BR et al.: Crystal structure of the angiogenesis inhibitor endostatin at 1.5 A resolution. Embo J 17: 1656–1664, 1998

    Google Scholar 

  130. Boehm T, Folkman J, Browder T et al.: Antiangiogenic therapy of experimental cancer does not induce acquired drug resistance [see comments]. Nature 390: 404–407, 1997

    Google Scholar 

  131. O'Leary J, Shapiro R, Ren C et al.: Antiangiogenic effects of camptothecin analogues 9-Amino-20(S)-camptothecin, Topotecan, and CPT-11 studies in the mouse cornea model. Clin Cancer Res 5: 181–187, 1999

    Google Scholar 

  132. Belotti D, Nicoletti I, Vergani V et al.: Paclitaxel (Taxol), a microtubule affecting drug, inhibits tumor angiogenesis. Proc Am Assoc Cancer Res 37: 57, 1996

    Google Scholar 

  133. Klauber N, Parangi S, Flynn E et al.: Inhibition of angiogenesis and breast cancer in mice by the microtubule inhibitors 2-methoxyestradiol and taxol. Cancer Res 57: 81–86, 1997

    Google Scholar 

  134. Benbow U, Maitra R, Hamilton J et al.: Selective modulation of collagenase I gene expression by the chemotherapeutic agent doxorubicin. Clin Cancer Res 5: 203–208, 1999

    Google Scholar 

  135. Haran EF, Maretzek AF, Goldberg I et al.: Tamoxifen enhances cell death in implanted MCF7 breast cancer by inhibiting endothelium growth. Cancer Res 54: 5511–5514, 1994

    Google Scholar 

  136. Gagliardi AR, Hennig B, Collins DC: Antiestrogens inhibit endothelial cell growth stimulated by angiogenic growth factors. Anticancer Res 16: 1101–1106, 1996

    Google Scholar 

  137. Dinney CP, Bielenberg DR, Perrotte P et al.: Inhibition of basic fibroblast growth factor expression, angiogenesis, and growth of human bladder carcinoma in mice by systemic interferon-alpha administration. Cancer Res 58: 808–814, 1998

    Google Scholar 

  138. Yoshida A, Anand-Apte B, Zetter BR: Differential endothelial migration and proliferation to basic fibroblast growth factor and vascular endothelial growth factor. Growth Factors 13: 57–64, 1996

    Google Scholar 

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Authors
  1. Kathy D. Miller
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  2. George W. Sledge Jr.
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Miller, K.D., Sledge, G.W. Toward Checkmate: Biology and Breast Cancer Therapy for the New Millennium. Invest New Drugs 17, 417–427 (1999). https://doi.org/10.1023/A:1006311227965

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