Skip to main content

Advertisement

SpringerLink
Log in

Vascular endothelial growth factor and bevacitumab in breast cancer

  • Review Article
  • Published:
Breast Cancer Aims and scope Submit manuscript

Abstract

Cancer development requires neovascularization. The level of angiogenic activity in breast cancer has been shown to be a determinant of disease progression and survival. Vascular endothelial growth factor (VEGF) is a one of the most essential pro-angiogenic growth factors expressed by most cancer-cell types and certain tumor stromal cells. Blocking the action of VEGF appears to be a promising anti-angiogenic approach to treat multiple types of solid tumors including breast cancer, and clinical trials using agents which target VEGF were launched beginning in the late 1990s. The effort reached fruition in 2005 with the first report of a large, prospective randomized trial of anti-VEGF therapy in patients with metastatic breast cancer (MBC), which demonstrated the benefit of adding the monoclonal antibody bevacizumab to the chemotherapeutic agent paclitaxel. The success of this trial provided proof of principle that inhibition of angiogenesis has the potential to enhance the effectiveness of treatment of this disease. Adjuvant thera-py trials are in development with bevacizumab and numerous other anti-VEGF agents are now being test-ed in patients with breast cancer in various settings. Nevertheless, since bevacizumab monotherapy has minimal activity, a question for future therapeutic development of these agents in breast cancer relates to the interaction between anti-angiogenic strategies and cytotoxic therapies. Further research is still need-ed for complete understanding of the exact role of VEGF and angiogenesis in health and disease, to take best advantage and avoid the adverse effects of anti-angiogenic therapy.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

Abbreviations

VEGF:

Vascular endothelial growth factor

VEGFR:

Vascular endothelial growth factor receptor

MBC:

Metastatic breast cancer

MVD:

Microvessel density

References

  1. Folkman J: (Tumor angiogenesis: therapeutic implications).N Engl J Med 285:1182–1186, 1971.

    Article  CAS  Google Scholar 

  2. Toi M, Matsumoto T, Bando H: (Vascular endothelial growth factor: its prognostic, predictive, and therapeutic implications).Lancet Oncol 2:667–673, 2001.

    Article  CAS  Google Scholar 

  3. Leung DW, Cachianes G, Kuang WJ, Goeddel DV, Ferrara N: (Vascular endothelial growth factor is a secreted angiogenic mitogen).Science 246:1306–1309, 1989.

    Article  CAS  Google Scholar 

  4. Ferrara N, Gerber HP, LeCouter J: (The biology of VEGF and its receptors).Nat Med 9:669–676, 2003.

    Article  CAS  Google Scholar 

  5. Ferrara N: (Molecular and biological properties of vascular endothelial growth factor).J Mol Med 77:527–543, 1999.

    Article  CAS  Google Scholar 

  6. Mura M, dos Santos CC, Stewart D, Liu M: (Vascular endothelial growth factor and related molecules in acute lung injury).J Appl Physiol 97:1605–1617, 2004.

    Article  CAS  Google Scholar 

  7. Ferrara N: (VEGF: an update on biological and therapeutic aspects).Cur Opin Biothech 11:517–524, 2000.

    Article  Google Scholar 

  8. Ferrara N, Alitalo K: (Clinical applications of angiogenic growth factors and their inhibitors).Nat Med 5:1359–1564, 1999.

    Article  CAS  Google Scholar 

  9. Achen MG, Jeltsch M, Kukk E, Makinen T, Vitali A, Wilks AF, Alitalo K, Stacker SA: (Vascular endothelial growth factor D (VEGF-D) is a ligand for the tyrosine kinases VEGF receptor 2 (Flkl) and VEGF receptor 3 (Flt4)).Proc Natl Acad Sci USA 95:548–553, 1998.

    Article  CAS  Google Scholar 

  10. Joukov V, Pajusola K, Kaipainen A, Chilov D, Lahti-nen I, Kukk E, Saksela O, Kalkkinen N, Alitalo K: (A novel vascular endothelial growth factor, VEGF-C, is a ligand for the Flt4 (VEGFR-3) and KDR (VEGFR-2) receptor tyrosine kinases).EMBOJ 15:290–298, 1996.

    CAS  Google Scholar 

  11. Gluzman-Poltorak Z, Cohen T, Shibuya M, Neufeld G: (Vascular endothelial growth factor receptor-1 (VEGFR-1) and neuropilin-2 form complexes).J Biol Chem 276:18688–18694, 2001.

    Article  CAS  Google Scholar 

  12. Bouck N, Stellmach V, Hsu SC: (How tumors become angiogenic).Adv Cancer Res 69:135–174, 1996.

    Article  CAS  Google Scholar 

  13. Rak J, Yu JL, Klement G, Kerbel RS: (Oncogenes and angiogenesis: signaling three-dimensional tumor growth).J Investig Dermatol Symp 5:24–33, 2005.

    Article  Google Scholar 

  14. Neufeld G, Cohen T, Gengrinovitch S, Poltorak Z: (Vascular endothelial growth factor (VEGF) and its receptors).Faseb J 13:9–22, 1999.

    Article  CAS  Google Scholar 

  15. Krieg M, Haas R, Brauch H, Acker T, Flamme I, Plate KH: (Up-regulation of hypoxia-inducible factors HIF-lalpha and HIF-2alpha under normoxic conditions in renal carcinoma cells by von Hippel-Lindau tumor suppressor gene loss of function).Oncogene 19:5435–5443, 2000.

    Article  CAS  Google Scholar 

  16. Shi Q, Le X, Abbruzzese JL, Peng Z, Qian CN, Tang H, Xiong Q, Wang B, Li XC, Xie K: (Constitutive Spl activity is essential for differential constitutive expression of vascular endothelial growth factor in human pancreatic adenocarcinoma).Cancer Res 61:4143–4154, 2001.

    CAS  PubMed  Google Scholar 

  17. Salven P, Orpana A, Joensuu H: (Leukocytes and platelets of patients with cancer contain high levels of vascular endothelial growth factor).Clin Cancer Res 5:487–591, 1999.

    CAS  PubMed  Google Scholar 

  18. Poon RT, Fan ST, Wong J: (Clinical implications of circulating angiogenic factors in cancer patients).J Clin Oncol 19:1207–1225, 2001.

    Article  CAS  Google Scholar 

  19. Mechtcheriakova D, Schabbauer G, Lucerna M, Clauss M, De Martin R, Binder BR, Hofer E: (Specificity, diversity, and convergence in VEGF and TNF-alpha signaling events leading to tissue factor up-reg-ulation via EGR-1 in endothelial cells).FASEB J 15:230–242, 2001.

    Article  CAS  Google Scholar 

  20. Contrino J, Hair G, Kreutzer DL, Rickles FR: (In situ detection of tissue factor in vascular endothelial cells: correlation with the malignant phenotype of human breast disease).Nat Med 2:209–215, 1996.

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  22. Jensen HM, Chen I, DeVault MR, Lewis AE: (Angiogenesis induced by “normal” human breast tissue: A probable marker for precancer).Science 218:293–295, 1982.

    Article  CAS  Google Scholar 

  23. Yoshiji H, Harris SR, Thorgeirsson UP: (Vascular endothelial growth factor is essential for initial but not continued in vivo growth of human breast carcinoma cells).Cancer Res 57:3924–3928, 1997.

    CAS  PubMed  Google Scholar 

  24. Bos R, Zhong H, Hanrahan CF, Mommers EC, Sem-enza GL, Pinedo HM, Abeloff MD, Simons JW, van Diest PJ, van der Wall E: (Levels of hypoxia-inducible factor-1 alpha during breast carcinogenesis).J Natl Cancer Inst 93:309–314, 2001.

    Article  CAS  Google Scholar 

  25. Guinebretiere JM, Le Monique G, Gavoille A, Bahi J, Contesso G: (Angiogenesis and risk of breast cancer in women with fibrocystic disease).J Natl Cancer Inst 86:635–636, 1994.

    Article  CAS  Google Scholar 

  26. Guidi AJ, Fischer L, Harris JR, Schnitt SJ: (Microves-sel density and distribution in ductal carcinoma in situ of the breast).J Natl Cancer Inst 86:614–619, 1994.

    Article  CAS  Google Scholar 

  27. Guidi AJ, Schnitt SJ, Fischer L, Tognazzi K, Harris JR, Dvorak HF, Brown LF: (Vascular permeability factor (vascular endothelial growth factor) expression and angiogenesis in patients with ductal carcinoma in situ of the breast).Cancer 80:1945–1953, 1997.

    Article  CAS  Google Scholar 

  28. Gasparini G: (Prognostic Value of Vascular Endothelial Growth Factor in Breast Cancer).Oncologist 5 Suppl 1:S37–44, 2000.

    Article  CAS  Google Scholar 

  29. Krippl P, Langsenlehner U, Renner W, Yazdani-Biuki B, Wolf G, Wascher TC, Paulweber B, Haas J, Samon-igg H: (A common 936 C/T gene polymorphism of vascular endothelial growth factor is associated with decreased breast cancer risk).Int J Cancer 106:468–471, 2003.

    Article  CAS  Google Scholar 

  30. Langsenlehner U, Samonigg H, Krippl P: Vascular endothelial growth factor gene polymorphism decreases the risk for breast cancer metastasis.Breast Cancer Res Treat 88:S72, 2004.

    Google Scholar 

  31. Foekens JA, Peters HA, Grebenchtchikov N, Look MP, Meijer-vanGelder ME, Geurts-Moespot A, van der Kwast TH, Sweep CG, Kijn JG: (High tumor levels of vascular endothelial growth factor predict poor response to systemic therapy in advanced breast cancer).Cancer Res 61:5407–5414, 2001.

    CAS  PubMed  Google Scholar 

  32. Gasparini G, Toi M, Miceli R, Vermeulen PB, Dittadi R, Biganzoli E, Morabito A, Fanelli M, Gatti C, Suzuki H, Tominaga T, Dirix LY, Gion M: Clinical relevance of vascular endothelial growth factor and thymidine phosphorylase in patients with node-positive breast cancer treated with either adjuvant chemotherapy or hormone therapy.Cancer J Sci Am 5:101–111, 1999.

    CAS  PubMed  Google Scholar 

  33. Linderholm B, Grankvist K, Wilking N, Johansson M, Tavelin B, Henriksson R: (Correlation of vascular endothelial growth factor content with recurrences, survival, and first relapse site in primary node-positive breast carcinoma after adjuvant treatment).J Clin Oncol 18:1423–1431, 2000.

    Article  CAS  Google Scholar 

  34. Zhang HT, Scott PA, Morbidelli L, Peak S, Moore J, Turley H, Harris AL, Ziche M, Bicknell R: (The 121 amino acid isoform of vascular endothelial growth factor is more strongly tumorigenic than other splice variants in vivo).Br J Cancer 83:63–68, 2000.

    Article  CAS  Google Scholar 

  35. Linderholm B, Tavelin B, Grankvist K, Henriksson R: Does vascular endothelial growth factor (VEGF) predict local relapse and survival in radiotherapy-treated node-negative breast cancer?Br J Cancer 81:727–732, 1999.

    Article  CAS  Google Scholar 

  36. Geng L, Donnelly E, McMahon G, Lin PC, Sierra-Rivera E, Oshinka H, Hallahan DE: (Inhibition of vascular endothelial growth factor receptor signaling leads to reversal of tumor resistance to radiotherapy).Cancer Res 61:2413–2419, 2001.

    CAS  PubMed  Google Scholar 

  37. Asahara T, Murohara T, Sullivan A, Silver M, van der Zee R, Li T, Witzenbichler B, Schatteman G, Isner JM: (Isolation of putative progenitor endothelial cells for angiogenesis).Science 275:964–967, 1997.

    Article  CAS  Google Scholar 

  38. Takahashi T, Kalka C, Masuda H, Chen D, Silver M, Kearney M, Magner M, Isner JM, Asahara T: (Ischemia-and cytokine-induced mobilization of bone marrow-derived endothelial progenitor cells for neovascularization).Nat Med 5:434–438, 1999.

    Article  CAS  Google Scholar 

  39. Gabrilovich DI, Chen HL, Girgis KR, Cunningham HT, Meny GM, Nadaf S, Kavanaugh D, Carbone DP: (Production of vascular endothelial growth factor by human tumors inhibits the functional maturation of dendritic cells).Nat Med 2:1096–1103, 1996.

    Article  CAS  Google Scholar 

  40. Gabrilovich DI, Ishida T, Nadaf S, Ohm JE, Carbone DP: (Antibodies to vascular endothelial growth factor enhance the efficacy of cancer immunotherapy by improving endogenous dendritic cell function).Clin Cancer Res 5:2963–2970, 1999.

    CAS  PubMed  Google Scholar 

  41. Yancopoulos GD, Davis S, Gale NW, Rudge JS, Wie-gand SJ, Holash J: (Vascular-specific growth factors and blood vessel formation).Nature 407:242–248, 2000.

    Article  CAS  Google Scholar 

  42. Ueno T, Toi M, Saji H, Muta M, Bando H, Kuroi K, Koike M, Inadera H, Matsushima K: (Significance of macrophage chemoattractant protein-1 in macrophage recruitment, angiogenesis, and survival in human breast cancer).Clin Cancer Res 6:3282–3289, 2000.

    CAS  PubMed  Google Scholar 

  43. Oshika Y, Masuda K, Tokunaga T, Hatanaka H, Kamiya T, Abe Y, Ozeki Y, Kijima H, Yamazaki H, Tamaoki N, Ueyama Y, Nakamura M: (Thrombosp-ondin 2 gene expression is correlated with decreased vascularity in non-small cell lung cancer).Clin Cancer Res 4:1785–1788, 1998.

    CAS  PubMed  Google Scholar 

  44. Volm M, Mattern J, Koomagi R: (Angiostatin expression in non-small cell lung cancer).Clin Cancer Res 6:3236–3240, 2000.

    CAS  PubMed  Google Scholar 

  45. Schneider BP, Miller KD: (Angiogenesis of breast cancer).J Clin Oncol 23:1782–1790, 2005.

    Article  CAS  Google Scholar 

  46. Haran EF, Maretzek AF, Goldberg I, Horowitz A, Degani H: (Tamoxifen enhances cell death in implanted MCF7 breast cancer by inhibiting endothelium growth).Cancer Res 54:5511–5514, 1994.

    CAS  PubMed  Google Scholar 

  47. Sweeney C, Sledge G: (Chemotherapy agents as anti-angiogenic therapy).Cancer Conference Highlights 3:2–4, 1999.

    Google Scholar 

  48. Slaton JW, Perrotte P, Inoue K, Dinney CP, Fidler IJ: (Interferon-alpha-mediated down-regulation of angio-genesis-related genes and therapy of bladder cancer are dependent on optimization of biological dose and schedule).Clin Cancer Res 5:2726–2734, 1999.

    CAS  PubMed  Google Scholar 

  49. Hanahan D, Bergers G, Bergsland E: (Less is more, regularly: Metronomic dosing of cytotoxic drugs can target tumor angiogenesis in mice).J Clin Invest 105:1045–1047, 2000.

    Article  CAS  Google Scholar 

  50. Colleoni M, Rocca A, Sandri MT, Zorzino L, Masci G, Nole F, Peruzzotti G, Robertson C, Orlando L, Cinieri S, de BF, Viale G, Goldhirsch A: (Low-dose oral methotrexate and cyclophosphamide in metastatic breast cancer: Antitumor activity and correlation with vascular endothelial growth factor levels).Ann Oncol 13:73–80, 2002.

    Article  CAS  Google Scholar 

  51. Ferrara N, Hillan KJ, Gerber HP, Novotny W: (Discovery and development of bevacizumab, an anti-VEGF antibody for treating cancer).Nat Rev Drug Discov 3:391–400, 2004.

    Article  CAS  Google Scholar 

  52. Hurwitz H, Fehrenbacher L, Novotny W, Cartwright T, Hainsworth J, Heim W, Berlin J, Baron A, Griffing S, Holmgren E, Ferrara N, Fyfe G, Rogers B, Ross R, Kabbinavar F: (Bevacizumab plus irinotecan, fluoro-uracil, and leucovorin for metastatic colorectal cancer).N Engl J Med 350:2335–2342, 2004.

    Article  CAS  Google Scholar 

  53. Gordon MS, Margolin K, Talpaz M, Sledge GW Jr, Holmgren E, Benjamin R, Stalter S, Shak S, Adelman D: (Phase I safety and pharmacokinetic study of recombinant human anti-vascular endothelial growth factor in patients with advanced cancer).J Clin Oncol 19:843–850, 2001.

    Article  CAS  Google Scholar 

  54. Margolin K, Gordon MS, Holmgren E, Gaudreault J, Novotny W, Fyfe G, Adelman D, Stalter S, Breed J: (Phase Ib trial of intravenous recombinant humanized monoclonal antibody to vascular endothelial growth factor in combination with chemotherapy in patients with advanced cancer: pharmacologic and long-term safety data).J Clin Oncol 19:851–856, 2001.

    Article  CAS  Google Scholar 

  55. Cobleigh MA, Langmuir VK, Sledge GW, Miller KD, Haney L, Novotny WF, Reimann JD, Vassel A: (A phase II dose-escalation trial of bevacizumab in previously treated metastatic breast cancer).Semin Oncol 30:117–124, 2003.

    Article  CAS  Google Scholar 

  56. Miller KD, Chap LI, Holmes FA, Cobleigh MA, Mar-com PK, Fehrenbacher L, Didder M, Overmoyer BA, Reimann JD, Sing AP, Langmuir L, Rugo HS: Randomized Phase IE trial of capecitabine compared with bevacizumab plus capecitabine in patients with previously treated metastatic breast cancer.J Clin Oncol 23:792–799, 2005.

    Article  CAS  Google Scholar 

  57. Miller KD, Wang M, Gralow J, Didder M, Cobleigh MA, Perez EA, Shenkier T, Davidson NE: A Randomized Phase IE Trial of Paclitaxel versus Paclitaxel plus Bevacizumab as First-Line Therapy for Locally Recurrent or Metastatic Breast Cancer: A Trial Coordinated by the Eastern Cooperative Oncology Group (E2100) Breast Cancer Research and Treatment, 94, Supplement 1, Abstract #3, 2005.

  58. Perez EA, Hillman DW, Kugler JW, Steen PD, Fitch TR, Rowland KM: North Central cancer treatment group (NCCTG) N0432: phase II trial of docetaxel with capecitabine and bevacizumab as first line chemotherapy for patients with metastatic breast cancer. Breast Cancer Research and Treatment, Supplement 1 Abstract #2069, 2006.

  59. Overmoyer B, Silverman P, Leeming R, Shenk R, Lyons J, Jesberger J, Hartman P, Dumadag L, Chen H: Phase II trial of neoadjuvant docetaxel with or without bevacizumab in patients with locally advanced breast cancer.Breast Cancer Res Treat 88:S106, Abstract #2088, 2004.

    Google Scholar 

  60. Silverman P, Lyons J, Fu P, Remick S, Chen H, Ziats N, Wasman J, Hartman P, Jesberger J, Leeming R, Shenk R, Dumadag L, Overmoyer B: Randomized phase II study of docetaxel ± bevacizumab for locally advanced unresectable breast cancer: impact on bio-markers of angiogenesis. Breast Cancer Research and Treatment, Supplement 1 Abstract #5086, 2006.

  61. Wedam SB, Low JA, Yang SX, Chow CK, Choyke P, Danforth D, Hewitt SM, Berman A, Steinberg SM, Liewehr DJ, Plehn J, Doshi A, Thomasson D, McCarthy N, Koeppen H, Sherman M, Zujewski J, Cam-phausen K, Chen H, Swain SM: (Phase II Trial of Bevacizumab in Combination with Weekly Docetaxel in Metastatic Breast Cancer Patients).J Clin Oncol 24:769–777, 2006.

    Article  CAS  Google Scholar 

  62. Koukourakis MI, Giatromanolaki A, O’Byrne KJ, Cox J, Krammer B, Gatter KC, Harris AL: (bcl-2 and c-erbB-2 proteins are involved in the regulation of VEGF and of thymidine phosphorylase angiogenic activity in non-small-cell lung cancer).Clin Exp Metastasis 17:545–554, 1999.

    Article  CAS  Google Scholar 

  63. Laughner E, Taghavi P, Chiles K, Mahon PC, Semen-za GL: (HER2 (neu) signaling increases the rate of hypoxia-inducible factor lalpha (HIF-lalpha) synthesis: Novel mechanism for HIF-1-mediated vascular endothelial growth factor expression).Mol Cell Biol 21:3995–4004, 2001.

    Article  CAS  Google Scholar 

  64. Konecny GE, Meng YG, Untch M, Wang HJ, Bauer-feind I, Epstein M, Stieber P, Vernes JM, Gutierrez J, Hong K, Beryt M, Hepp H, Slamon DJ, Pegram MD: (Association between HER-2/neu and vascular endothelial growth factor expression predicts clinical outcome in primary breast cancer patients).Clin Cancer Res 10:1706–1716, 2004.

    Article  CAS  Google Scholar 

  65. Pegram M, Yeon C, Ku N, Gaudreault J, Slamon DJ: Phase I combined biological therapy of breast cancer using two humanized monoclonal antibodies directed against HER2 proto-oncogene and vascular endothelial growth factor (VEGF).Breast Cancer Res Treat 88:S124, Abstract #3039, 2004.

    Google Scholar 

  66. Pegram M, Chan D, Dichmann RA, Tan-Chiu E, Yeon C, Durna L, Lin LS, Slamon D: Phase II combined biological therapy targeting the HER2 proto-oncogene and the vascular endothelial growth factor using trastuzumab (T) and bevacizumab (B) as first line treatment of HER2-amplified breast cancer. Breast Cancer Research and Treatment, Supplement 1 Abstract #3019, 2006.

  67. Maity A, Pore N, Lee J, Solomon D, O’Rourke DM: (Epidermal growth factor receptor transcriptionally up-regulates vascular endothelial growth factor expression in human glioblastoma cells via a pathway involving phosphatidylinositol 3’-kinase and distinct from that induced by hypoxia).Cancer Res 60:5879–5886, 2000.

    CAS  PubMed  Google Scholar 

  68. Clarke K, Smith K, Gullick WJ, Harris AL: (Mutant epidermal growth factor receptor enhances induction of vascular endothelial growth factor by hypoxia and insulin-like growth factor-1 via a PI3 kinase dependent pathway).Br J Cancer 84:1322–1329, 2001.

    Article  CAS  Google Scholar 

  69. Petit AM, Rak J, Hung MC, Rockwell P, Goldstein N, Fendly B, Kerbel RS: (Neutralizing antibodies against epidermal growth factor and ErbB-2/neu receptor tyrosine kinases down-regulate vascular endothelial growth factor production by tumor cells in vitro and in vivo: Angiogenic implications for signal transduction therapy of solid tumors).Am J Pathol 151:1523–1530, 1997.

    CAS  PubMed  PubMed Central  Google Scholar 

  70. Rugo H, Dickler M, Scott J, Moore DH, Park JW: Circulating endothelial cell (CEC) and tumor cell (CTC) analysis in patients (pts) receiving bevacizumab and erlotinib for metastatic breast cancer (MBC).Breast Cancer Res Treat 88:S142, Abstract #3088, 2004.

    Google Scholar 

  71. Jain RK, Duda DG, Clark JW, Loeffler JS: (Lessons from phase III clinical trials on anti-VEGF therapy for cancer).Nat Clin Pract Oncol 3:24–40, 2006.

    Article  CAS  Google Scholar 

  72. Jain RK: (Normalization of tumor vasculature: An emerging concept in antiangiogenic therapy).Science 307:58–62, 2005.

    Article  CAS  Google Scholar 

  73. Sweeney CJ, Miller KD, Sissons SE, Nozaki S, Heil-man DK, Shen J, Sledge GW Jr: (The antiangiogenic property of docetaxel is synergistic with a recombinant humanized monoclonal antibody against vascular endothelial growth factor or 2-methoxyestradiol but antagonized by endothelial growth factors).Cancer Res 61:3369–3372, 2001.

    CAS  PubMed  Google Scholar 

  74. Weng D, Weiss P, Kellackey C: Angiozyme pharmacokinetic and safety results: A phase I/II study in patients with refractory solid tumors.Proc Am Soc Clin Oncol 20:99a, 2001 (abstr 393).

    Google Scholar 

  75. Sparano JA, Bernardo P, Stephenson P, Gradishar WJ, Ingle JN, Zucker S, Davidson NE: (Randomized phase HI trial of marimastat versus placebo in patients with metastatic breast cancer who have responding or stable disease after first-line chemotherapy: Eastern Cooperative Oncology Group trial E2196).J Clin Oncol 22:4631–4638, 2004.

    Article  Google Scholar 

  76. Midgley R, Kerr D: (Bevacizumab-current status and future directions).Ann Oncol 16:999–1004, 2005.

    Article  Google Scholar 

  77. Carmeliet P: (Angiogenesis in life, disease and medicine).Nature 438:932–936, 2005.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Breast and Endocrine Surgery, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Japan

    Hiroko Bando

Authors
  1. Hiroko Bando
    View author publications

    You can also search for this author in PubMed Google Scholar

About this article

Cite this article

Bando, H. Vascular endothelial growth factor and bevacitumab in breast cancer. Breast Cancer 14, 163–173 (2007). https://doi.org/10.2325/jbcs.968

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.2325/jbcs.968

Key words

Search

Navigation