Cancer Treatment Reviews
Volume 36, Issue 1 , Pages 75-82 , February 2010

Bevacizumab in the treatment of breast cancer

  • Angelos K. Koutras

      Affiliations

    • Division of Oncology, Department of Medicine, University Hospital, Patras Medical School, Rion 26504, Greece
    • Corresponding Author InformationCorresponding author. Tel.: +30 2610999535; fax: +30 2610994645.
    • ,
  • George Fountzilas

      Affiliations

    • Department of Medical Oncology, Papageorgiou Hospital, Aristotle University of Thessaloniki School of Medicine, Thessaloniki, Greece
    • Tel.: +30 2310693134.
    • ,
  • Thomas Makatsoris

      Affiliations

    • Division of Oncology, Department of Medicine, University Hospital, Patras Medical School, Rion 26504, Greece
    • Tel.: +30 2610999535; fax: +30 2610994645.
    • ,
  • Stavros Peroukides

      Affiliations

    • Division of Oncology, Department of Medicine, University Hospital, Patras Medical School, Rion 26504, Greece
    • Tel.: +30 2610999535; fax: +30 2610994645.
    • ,
  • Haralabos P. Kalofonos

      Affiliations

    • Division of Oncology, Department of Medicine, University Hospital, Patras Medical School, Rion 26504, Greece
    • Tel.: +30 2610999535; fax: +30 2610994645.

Received 12 July 2009 ,Revised 25 October 2009 ,Accepted 27 October 2009.

References 

  1. Folkman J. Angiogenesis in cancer, vascular, rheumatoid and other disease. Nat Med. 1996;1:27–31
  2. Ferrara N. VEGF and the quest for tumour angiogenesis factors. Nat Rev Cancer. 2002;2:795–803
  3. Hicklin DJ, Ellis LM. Role of the vascular endothelial growth factor pathway in tumor growth and angiogenesis. J Clin Oncol. 2005;23:1011–1027
  4. Shibuya M, Claesson-Welsh L. Signal transduction by VEGF receptors in regulation of angiogenesis and lymphangiogenesis. Exp Cell Res. 2006;312:549–560
  5. Kerbel RS. Tumor angiogenesis. N Engl J Med. 2008;358:2039–2049
  6. 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. 1997;57:963–969
  7. Yoshiji H, Gomez DE, Shibuya M, Thorgeirsson UP. Expression of vascular endothelial growth factor, its receptor, and other angiogenic factors in human breast cancer. Cancer Res. 1996;56:2013–2016
  8. Ferrara N, Gerber HP, LeCouter J. The biology of VEGF and its receptors. Nat Med. 2003;9:669–676
  9. Drevs J. VEGF and angiogenesis: implications for breast cancer therapy. Eur J Cancer. 2008;6(Suppl. 6):7–13
  10. Inai T, Mancuso M, Hashizume H, et al. Inhibition of vascular endothelial growth factor (VEGF) signaling in cancer causes loss of endothelial fenestrations, regression of tumor vessels, and appearance of basement membrane ghosts. Am J Pathol. 2004;165:35–52
  11. Jain RK. Normalization of tumor vasculature: an emerging concept in antiangiogenic therapy. Science. 2005;307:58–62
  12. Wildiers H, Guetens G, De Boeck G, et al. Effect of antivascular endothelial growth factor treatment on the intratumoral uptake of CPT-11. Br J Cancer. 2003;88:1979–1986
  13. Dallas NA, Fan F, Gray MJ, et al. Functional significance of vascular endothelial growth factor receptors on gastrointestinal cancer cells. Cancer Metast Rev. 2007;26:433–441
  14. Rovati B, Manzoni M, Bencardino K, et al. The effect of bevacizumab plus chemotherapy on the immunological profile of advanced colorectal cancer patients. J Clin Oncol. 2008;26(20 Suppl.):[Abstract 14579]
  15. Wedam SB, Low JA, Yang SX, et al. Antiangiogenic and antitumor effects of bevacizumab in patients with inflammatory and locally advanced breast cancer. J Clin Oncol. 2006;24:769–777
  16. Saltz LB, Clarke S, Díaz-Rubio E, et al. Bevacizumab in combination with oxaliplatin-based chemotherapy as first-line therapy in metastatic colorectal cancer: a randomized phase III study. J Clin Oncol. 2008;26:2013–2019
  17. Miles D, Chan A, Romieu G, et al. Randomized, double-blind, placebo-controlled, phase III study of bevacizumab with docetaxel or docetaxel with placebo as first-line therapy for patients with locally recurrent or metastatic breast cancer (mBC): AVADO. J Clin Oncol. 2008;26(20 Suppl.):[Abstract LBA1011]
  18. Fumoleau P, Greil R, Rayson D, et al. Bevacizumab (BV) maintenance therapy significantly delays disease progression (PD) or death compared with placebo (PL) in the AVADO trial (BV+docetaxel [D] vs. D+PL in 1st-line HER2-negative locally recurrent [LR] or metastatic breast cancer [mBC]). Program and abstracts of the 31st annual San Antonio breast cancer symposium, December 10–14, 2008, San Antonio, Texas [Abstract 903].
  19. Kamba T, Tam BY, Hashizume H, et al. VEGF-dependent plasticity of fenestrated capillaries in the normal adult microvasculature. Am J Physiol Heart Circulatory Physiol. 2006;290:H560–H576
  20. Ran S, Bivens C, Trieu V, Desai N. Synergistic effect of albumin-bound paclitaxel (abraxane) and anti-VEGF-A antibody (avastin) on growth of orthotopic MDA-MB-231 breast tumors as well as lymphatic and pulmonary disease. Program and abstracts of the 29th annual San Antonio breast cancer symposium, December 14–17, 2006, San Antonio, Texas [Abstract 1094].
  21. Higgins B, Kolinsky K, Zhang Y-E, Moisa C, Dugan U, Packman K. Antitumor activity of a combined regimen of capecitabine and bevacizumab in a xenograft model of human breast cancer. Program and abstracts of the 29th annual San Antonio breast cancer symposium, December 14–17, 2006, San Antonio, Texas [Abstract 6116].
  22. Miller KD, Wang M, Gralow J, et al. Paclitaxel plus bevacizumab versus paclitaxel alone for metastatic breast cancer. N Engl J Med. 2007;357:2666–2676
  23. Greil R, Im Y, Pienkowski T, et al. Quality of life among patients with locally recurrent or metastatic breast cancer: results from the phase III AVADO study of first-line bevacizumab plus docetaxel versus docetaxel plus placebo. Ann Oncol. 2008;19(Suppl. 8):[Abstract 147P]
  24. Pivot X, Verma S, Thomssen C, et al. Clinical benefit of bevacizumab+first-line docetaxel in elderly patients with locally recurrent (LR) or metastatic breast cancer (MBC): AVADO study. J Clin Oncol. 2009;27(15s):[Abstract 1094]
  25. Robert NJ, Dieras V, Glaspy J, et al. RIBBON-1: randomized, double-blind, placebo-controlled, phase III trial of chemotherapy with or without bevacizumab (B) for first-line treatment of HER2-negative locally recurrent or metastatic breast cancer (MBC). J Clin Oncol. 2009;27(15s):[Abstract 1005]
  26. Smith IE, Biganzoli L, Cortes-Funes H, et al. Primary analysis of study MO19391, a 2000-patient open-label safety study of bevacizumab plus taxane-based therapy as first-line treatment of patients with locally recurrent or metastatic breast cancer. Program and abstracts of the 31st annual San Antonio breast cancer symposium, December 10–14, 2008, San Antonio, Texas [Abstract 4118].
  27. Miller KD, Chap LI, Holmes FA, et al. Randomized phase III trial of capecitabine compared with bevacizumab plus capecitabine in patients with previously treated metastatic breast cancer. J Clin Oncol. 2005;23:792–799
  28. O’Shaughnessy JA, Brufsky AM. RiBBON 1 and RiBBON 2: phase III trials of bevacizumab with standard chemotherapy for metastatic breast cancer. Clin Breast Cancer. 2008;8:370–373
  29. Dellapasqua S, Bertolini F, Bagnardi V, et al. Metronomic cyclophosphamide and capecitabine combined with bevacizumab in advanced breast cancer. J Clin Oncol. 2008;26:4899–4905[Epub 2008 September 15]
  30. García-Sáenz JA, Martín M, Calles A, et al. Bevacizumab in combination with metronomic chemotherapy in patients with anthracycline- and taxane-refractory breast cancer. J Chemother. 2008;20:632–639
  31. Shaked Y, Emmenegger U, Man S, et al. Optimal biologic dose of metronomic chemotherapy regimens is associated with maximum antiangiogenic activity. Blood. 2005;106:3058–3061
  32. Russell KS, Stern DF, Polverini PJ, Bender JR. Neuregulin activation of ErbB receptors in vascular endothelium leads to angiogenesis. Am J Physiol. 1999;277(Pt 2):H2205–H2211
  33. Yen L, You XL, Al Moustafa AE, et al. Heregulin selectively upregulates vascular endothelial growth factor secretion in cancer cells and stimulates angiogenesis. Oncogene. 2000;19:3460–3469
  34. Finkenzeller G, Weindel K, Zimmermann W, Westin G, Marmé D. Activated Neu/ErbB-2 induces expression of the vascular endothelial growth factor gene by functional activation of the transcription factor Sp 1. Angiogenesis. 2004;7:59–68
  35. Klos KS, Wyszomierski SL, Sun M, et al. ErbB2 increases vascular endothelial growth factor protein synthesis via activation of mammalian target of rapamycin/p70S6K leading to increased angiogenesis and spontaneous metastasis of human breast cancer cells. Cancer Res. 2006;66:2028–2037
  36. Scheuer W, Friess T, Hasmann M. Enhanced antitumour effect by combination of HER2-targeting antibodies with bevacizumab in a human breast cancer xenograft model. Eur J Cancer. 2006;4(Suppl.):66;[Abstract 213]
  37. Pegram M, Chan D, Dichmann RA, et al. Phase II combined biological therapy targeting the HER2 protooncogene and the vascular endothelial growth factor using trastuzumab (T) and bevacizumab (B) as first line treatment of HER2-amplified breast cancer. Breast Cancer Res Treat. 2006;100(Suppl. 1):S28;[Abstract 301]
  38. Rugo HS, Franco S, Munster P, et al. A phase II evaluation of lapatinib (L) and bevacizumab (B) in HER+ metastatic breast cancer (MBC). J Clin Oncol. 2008;26(20 Suppl.):[Abstract 1042]
  39. Shweiki D, Itin A, Neufeld G, Gitay-Goren H, Keshet E. Patterns of expression of vascular endothelial growth factor (VEGF) and VEGF receptors in mice suggest a role in hormonally regulated angiogenesis. J Clin Invest. 1993;91:2235–2243
  40. Hyder SM, Nawaz Z, Chiappetta C, Stancel GM. Identification of functional estrogen response elements in the gene coding for the potent angiogenic factor vascular endothelial growth factor. Cancer Res. 2000;60:3183–3190
  41. Takei H, Lee ES, Jordan VC. In vitro regulation of vascular endothelial growth factor by estrogens and antiestrogens in estrogen-receptor positive breast cancer. Breast cancer. 2002;9:39–42
  42. Nakamura J, Savinov A, Lu Q, Brodie A. Estrogen regulates vascular endothelial growth/permeability factor expression in 7,12-dimethylbenz(a)anthracene induced rat mammary tumors. Endocrinology. 1996;137:5589–5596
  43. Pietras RJ, Chen H-W, Marquez DC. Improved anticancer therapy by targeting both breast tumor and host vascular cells with antiestrogen combined with antibodies to vascular endothelial growth factor. Program and abstracts of the 29th annual San Antonio breast cancer symposium, December 14–17, 2006, San Antonio, Texas [Abstract 507].
  44. Traina TA, Rugo H, Caravelli J, et al. Letrozole (L) with bevacizumab (B) is feasible in patients (pts) with hormone receptor-positive metastatic breast cancer (MBC). J Clin Oncol. 2006;24(20 Suppl.):133s;[Abstract 3050]
  45. Yardley DA, Peacock N, Arrowsmith E, et al. Preliminary safety results from a multicenter phase II noncomparative two arm pilot of bevacizumab with anastrozole or fulvestrant as 1st line metastatic breast cancer therapy. Program and abstracts of the 31st annual San Antonio breast cancer symposium, December 10–14, 2008, San Antonio, Texas [Abstract 4113].
  46. Miller KD, O’Neill A, Perez EA, et al. Phase II feasibility trial incorporating bevacizumab into dose dense doxorubicin and cyclophosphamide followed by paclitaxel in patients with lymph node positive breast cancer: a trial of the Eastern Cooperative Oncology Group (E2104). Breast Cancer Res Treat. 2007;106(Suppl. 1):S147;[Abstract 3063]
  47. Makhoul I, Vicki KS, Korourian S, et al. Bevacizumab combined with chemotherapy significantly improves pathologic complete response in patients with operable or locally advanced breast cancer. Program and abstracts of the 31st annual San Antonio breast cancer symposium, December 10–14, 2008, San Antonio, Texas [Abstract 5114].
  48. Burstein HJ, Chen YH, Parker LM, et al. VEGF as a marker for outcome among advanced breast cancer patients receiving anti-VEGF therapy with bevacizumab and vinorelbine chemotherapy. Clin Cancer Res. 2008;14:7871–7877
  49. Schneider BP, Wang M, Radovich M, et al. Association of vascular endothelial growth factor and vascular endothelial growth factor receptor-2 genetic polymorphisms with outcome in a trial of paclitaxel compared with paclitaxel plus bevacizumab in advanced breast cancer: ECOG 2100. J Clin Oncol. 2008;26:4672–4678
  50. Schultheis AM, Lurje G, Rhodes KE, et al. Polymorphisms and clinical outcome in recurrent ovarian cancer treated with cyclophosphamide and bevacizumab. Clin Cancer Res. 2008;14:7554–7563
  51. Torrisi R, Bagnardi V, Cardillo A, et al. Preoperative bevacizumab combined with letrozole and chemotherapy in locally advanced ER- and/or PgR-positive breast cancer: clinical and biological activity. Br J Cancer. 2008;99:1564–1571
  52. Friberg G, Kasza K, Vokes EE, Kindler L. Early hypertension (HTN) as a potential pharmacodynamic (PD) marker for survival in pancreatic cancer (PC) patients (pts) treated with bevacizumab (B) and gemcitabine (G). J Clin Oncol. 2005;23(1 Suppl.):[Abstract 3020]
  53. Scartozzi M, Galizia E, Chiorrini S, et al. Arterial hypertension correlates with clinical outcome in colorectal cancer patients treated with first-line bevacizumab. Ann Oncol. 2009;20:227–230
  54. Bono P, Elfving H, Utriainen T, et al. Hypertension and clinical benefit of bevacizumab in the treatment of advanced renal cell carcinoma. Ann Oncol. 2009;20:393–394
  55. Grothey A, Sugrue MM, Purdie DM, et al. Bevacizumab beyond first progression is associated with prolonged overall survival in metastatic colorectal cancer: results from a large observational cohort study (BRiTE). J Clin Oncol. 2008;26:5326–5334
  56. Ellis LM, Hicklin DJ. Pathways mediating resistance to vascular endothelial growth factor – targeted therapy. Clin Cancer Res. 2008;14:6371–6375
  57. Casanovas O, Hicklin DJ, Bergers G, Hanahan D. Drug resistance by evasion of antiangiogenic targeting of VEGF signaling in late-stage pancreatic islet tumors. Cancer Cell. 2005;8:299–309
  58. Fischer C, Jonckx B, Mazzone M, et al. Anti-PlGF inhibits growth of VEGF(R)-inhibitor-resistant tumors without affecting healthy vessels. Cell. 2007;131:463–475
  59. Bergers G, Hanahan D. Modes of resistance to anti-angiogenic therapy. Nat Rev Cancer. 2008;8:592–603
  60. Ridgway J, Zhang G, Wu Y, et al. Inhibition of Dll4 signalling inhibits tumour growth by deregulating angiogenesis. Nature. 2006;444:1083–1087
  61. Grunewald M, Avraham I, Dor Y, et al. VEGF-induced adult neovascularization: recruitment, retention, and role of accessory cells. Cell. 2006;124:175–189
  62. Reinmuth N, Liu W, Jung YD, et al. Induction of VEGF in perivascular cells defines a potential paracrine mechanism for endothelial cell survival. FASEB J. 2001;15:1239–1241
  63. Miles D. Management of toxicity in patients receiving therapy with bevacizumab. Eur J Cancer. 2008;6(Suppl.):29–39
  64. Purdie DM, Berlin JD, Flynn PJ, et al. The safety of long-term bevacizumab use: results from the BRiTE observational cohort study (OCS). J Clin Oncol. 2008;26(20 Suppl.):[Abstract 4103]
  65. Hood JD, Meininger CJ, Ziche M, Granger HJ. VEGF upregulates ecNOS message, protein, and NO production in human endothelial cells. Am J Physiol. 1998;274(3 Pt 2):H1054–H1058
  66. Dincer M, Altundag K. Angiotensin-converting enzyme inhibitors for bevacizumab-induced hypertension. Ann Pharmacother. 2006;40:2278–2279
  67. Biganzoli L, Cortes-Funes H, Thomssen C, et al. Tolerability and efficacy of first-line bevacizumab (B) plus chemotherapy (CT) in elderly patients with advanced breast cancer (aBC): subpopulation analysis of the MO19391 study. J Clin Oncol. 2009;27(15s):[Abstract 1032]
  68. Eremina V, Sood M, Haigh J, et al. Glomerular-specific alterations of VEGF-A expression lead to distinct congenital and acquired renal diseases. J Clin Invest. 2003;111:707–716
  69. Flynn PJ, Sugrue MM, Feng S, et al. Incidence of serious bleeding events (sBE) in patients (pts) with metastatic colorectal cancer (mCRC) receiving bevacizumab (BV) as part of a first-line regimen: results from the BRiTE observational cohort study (OCS). J Clin Oncol. 2008;26(20 Suppl.):[Abstract 4104]
  70. Vredenburgh JJ, Desjardins A, Herndon JE, et al. Bevacizumab plus irinotecan in recurrent glioblastoma multiforme. J Clin Oncol. 2007;25:4722–4729
  71. Dirix LY, Romieu G, Provencher L, et al. Safety of bevacizumab (BV) plus docetaxel (D) in patients (pts) with locally recurrent (LR) or metastatic breast cancer (mBC) who developed brain metastases during the AVADO phase III study. Program and abstracts of the 31st annual San Antonio breast cancer symposium, December 10–14, 2008, San Antonio, Texas [Abstract 4116].
  72. Rohr UP, Augustus S, Lasserre SF, et al. Safety of bevacizumab in patients with metastases to the central nervous system. J Clin Oncol. 2009;27(15s):[Abstract 2007]
  73. Labidi SI, Bachelot T, Ray-Coquard I, et al. Bevacizumab and paclitaxel for breast cancer patients with central nervous system metastases: a case series. Clin Breast Cancer. 2009;9:118–121
  74. Skillings JR, Johnson DH, Miller K, et al. Arterial thromboembolic events (ATEs) in a pooled analysis of 5 randomized, controlled trials (RCTs) of bevacizumab (BV) with chemotherapy. J Clin Oncol. 2005;23(1 Suppl.):[Abstract 3019]
  75. Kamba T, McDonald DM. Mechanisms of adverse effects of anti-VEGF therapy for cancer. Br J Cancer. 2007;96:1788–1795
  76. Greuter S, Schmid F, Ruhstaller T, Thuerlimann B. Bevacizumab-associated osteonecrosis of the jaw. Ann Oncol. 2008;19:2091–2092
  77. Christodoulou C, Pervena A, Klouvas G, et al. Combination of bisphosphonates and antiangiogenic factors induces osteonecrosis of the jaw more frequently than bisphosphonates alone. Oncology. 2009;76:209–211
  78. McArthur HL, Estilo C, Huryn J, et al. Osteonecrosis of the jaw (ONJ) among intravenous (IV) bisphosphonate- and/or bevacizumab-treated patients (pts) at Memorial Sloan-Kettering Cancer Center (MSKCC). J Clin Oncol. 2008;26(20 Suppl.):[Abstract 9588]

PII: S0305-7372(09)00160-1

doi: 10.1016/j.ctrv.2009.10.007

Cancer Treatment Reviews
Volume 36, Issue 1 , Pages 75-82 , February 2010

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