1. Miller K, Wang M, Gralow J et al. Paclitaxel plus bevacizumab versus paclitaxel alone for metastatic breast cancer. N Engl J Med 2007; 357(26): 2666–2676.
2. Hanahan D, Weinberg RA. The hallmarks of cancer. Cell 2000; 100(1): 57–70.
3. 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 1997; 89(2): 139–147.
4. Linderholm B, Grankvist K, Wilking N et al. 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 2000; 18(7): 1423–1431.
5. Foekens JA, Peters HA, Grebenchtchikov N et al. High tumor levels of vascular endothelial growth factor predict poor response to systemic therapy in advanced breast cancer. Cancer Res 2001; 61(14): 5407–5414.
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(5): 963–969.
7. Konecny EG, Meng YG, Untch M et al. Association between HER-2/neu and vascular endothelial growth factor expression predicts clinical outcome in primary breast cancer patients. Clin Cancer Res 2004;10(5): 1706–1716.
8. Linderholm BK, Hellborg H, Johansson U et al. Significiantly higher levels of vascular endothelial growth factor (VEGF) and shorter survival times for patients with primary operable triple-negative breast cancer. Ann Oncol 2009; 20(10): 1639–1646.
9. Boneberg EM, Legler DF, Hoefer MM et al. Angiogenesis and lymphangiogenesis are downregulated in primary breast cancer. Br J Cancer 2009; 101(4): 605–614.
10. Bergers G, Hanahan D. Modes of resistance to anti-angiogenic therapy. Nat Rev Cancer 2008; 8(8): 592–603.
11. Mueller MD, Vigne JL, Minchenko A et al. Regulation of vascular endothelial growth factor (VEGF) gene transcription by estrogen receptors alfa and beta. Proc Natl Acad Sci USA 2000; 97(20): 10972–10977.
12. 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(4): 2028–2037.
13. Ferrara N, Gerber HP, LeCouter J. The biology of VEGF and its receptors. Nat Med 2003; 9: 669–676.
14. Moore A. Breast-cancer therapy – looking back to the future. N Engl J Med 2007; 357(15): 1547–1549.
15. Brown LF, Berse B, Jackman RW et al. Expression of vascular permeability factor (vascular endothelial growth factor) and its receptor in breast cancer. Hum Pathol 1995; 26(1): 86–91.
16. Pavlakis K, Messini I, Vrekoussis T et al. The assessment of angiogenesis and fibroblastic stromagenesis in hyperplastic and pre-invasive breast lesions. BMC Cancer 2008; 8: 88.
17. Eyler CE, Rich JN. Survival of the Fittest: Cancer stem cells in therapeutic resistance and angiogenesis. J Clin Oncol 2008; 26(17): 2839–2845.
18. Kaufmann M, von Minckwitz G, Smith R et al. International expert panel on the use of primary (preoperative) systemic treatment of operable breast cancer: review and recommendations. J Clin Oncol 2003; 21(13): 2600–2608.
19. Derleth C, Mayer IA. Antiangiogenic therapies in early-stage breast cancer. Clin Breast Cancer 2010; 10 (Suppl 1): E23–E31.
20. Bear HD, Tang G, Rastogi P et al. Bevacizumab added to neoadjuvant chemotherapy for breast cancer. N Engl J Med 2012; 366(4): 310–320.
21. von Minckwitz G, Eidtmann H, Rezai M et al. German Breast Group; Arbeitsgemeinschaft Gynäkologische Onkologie–Breast Study Groups. Neoadjuvant chemotherapy and bevacizumab for HER2-negative breast cancer. N Engl J Med 2012; 366(4): 299–309.
22. Untch M, Fasching PA, Konecny GE et al. Pathologic complete response after neoadjuvant chemotherapy plus trastuzumab predicts favorable survival in human epidermal growth factor receptor 2-overexpressing breast cancer: results of the TECHNO trial of the AGO and CGC study groups. J Clin Oncol 2011; 29(25): 3351–3357.
23. Liedtke C, Mazouni C, Hess KR et al. Response to neoadjuvant therapy and long-term survival in patients with triple-negative breast cancer. J Clin Oncol 2008; 26(8): 1275–1281.
24. Mayer EL, Miller K, Rugo H et al. A pilot study of adjuvantn bevacizumab and chemotherapy after neoadjuvant chemotherapy for high-risk breast cancer. J Clin Oncol 2008; 26 (Suppl 15): s11, Abstract 519.
25. Scappaticci FA, Skillings JR, Holden SN et al. Arterial thromboembolic events in patients with metastatic carcinoma treated with chemotherapy and bevacizumab. J Natl Cancer Inst 2007; 99(16): 1232–1239.
26. Nalluri SR, Chu D, Keresztes R et al. Risk of venous thromboembolism with the angiogenesis inhibitor bevacizumab in cancer patients: a meta-analysis. JAMA 2008; 300(19): 2277–2285.
27. O‘Shaughnessy J, Miles D, Gray RJ et al. A meta-analysis of overall survival data from three randomized trials of bevacizumab (BV) and first-line chemotherapy as treatment for patients with metastatic breast cancer (MBC). J Clin Oncol 2010; 28 (Suppl): 15s, Abstract 1005.
28. Miller KD, Chap LI, Holmes FA et al. Randomized pha-se III trial of capecitabine compared with bevacizumab plus capecitabine in patients with previously treated metastatic breast cancer. J Clin Oncol 2005; 23(4): 792–799.
29. Muta M, Yanagawa T, Sai Y et al. Effect of low-dose paclitaxel and docetaxel on endothelial progenitor cells. Oncology 2009; 77(3–4): 182–191.
30. Ranpura V, Hapani S, Wu S. Treatment-related mortality with bevacizumab in cancer patients: a meta-analysis. JAMA 2011; 305(58): 487–494.
31. Ebos JM, Lee CR, Cruz-Munoz W et al. Accelerated metastasis after short-term treatment with a potent inhibitor of tumor angiogenesis. Cancer Cell 2009; 15(3): 232–239.
32. Páez-Ribes M, Allen E, Hudock J et al. Antiangiogenic therapy elicits malignant progression of tumors to increased local invasion and distant metastasis. Cancer Cell 2009; 15(3): 220–231.
33. Mancuso MR, Davis R, Norberg SM et al. Rapid vascular regrowth in tumors after reversal of VEGF inhibition. J Clin Invest 2006; 116(10): 2610–2621.
34. Ebos JM, Kerbel RS. Antiangiogenic therapy: Impact on invasion, disease progression, and metastasis. Nat Rev Clin Oncol 2011; 8(4): 210–221.
35. Miles D, Harbeck N, Escudier B et al. Disease course patterns after discontinuation of bevacizumab: pooled analysis of randomized phase III trials. J Clin Oncol 2011; 29: 83–88.
36. Pasquier E, Kavallaris M, André N. Metronomic chemotherapy: New rationale for new directions. Nat Rev Clin Oncol 2010; 7(8): 455–465.
37. Kerbel RS, Kamen BA. The anti-angiogenc basis of metronomic chemotherapy. Nat Rev Cancer 2004; 4(6): 423–436.
38. Dellapasqua S, Bertolini F, Bagnardi V et al. Metronomic cyclophosphamide and capecitabine combined with bevacizumab in advanced breast cancer. J Clin Oncol 2008; 26(30): 4899–4905.
39. Bagri A, Berry L, Gunter B et al. Effects of anti-VEGF treatment duration on tumor growth, tumor regrowth, and treatment efficacy. Clin Cancer Res 2010; 16(15): 3887–3900.
40. Von Minckwitz G, Rezai M, Fasching PA et al. Neoadjuvant chemotherapy with or without bevacizumab: primary efficacy endpoint analysis of the GEPARQUINTO study (CBG 44). Cancer Res 2010; 70 (Suppl): 86, Abstract 235.
41. Munoz R, Man S, Shaked Y et al. Highly efficacious nontoxic preclinical treatment for advanced metastatic breast cancer using combination oral UFT-cyclophosphamide metronomic chemotherapy. Cancer Res 2006; 66(7): 3386–3391.
42. Rosen LS, Ashurts HL, Chap L. Targeting signal transduction pathways in metastatic breast cancer: A comprehensive review. Oncologist 2010; 16(3): 216–235.
43. Schneider BP, Sledge GW Jr. Anti-VEGF therapy as adjuvant therapy: Clouds on the horizon? Breast Cancer Res 2009; 11(3): 303.
44. Ocaña A, Amir E, Vera F et al. Addition of bevacizumab to chemotherapy for treatment of solid tumors: similar results but different conclusions. J Clin Oncol 2011; 29(3): 254–256.
45. Casanovas O, Hicklin DJ, Bergers D et al. Drug resistance by evasion of antiangiogenic targeting of VEGF signaling in late-stage pancreatic islet tumors. Cancer Cell 2005; 8(4): 299–309.
46. Jain RK, Duda DG, Willet CG et al. Biomarkers of response and resistance to antiangiogenic therapy. Nat Rev Clin Oncol 2009; 6(6): 327–338.
47. Jubb AM, Harris AL. Biomarkers to predict the clinical efficacy of bevacizumab in cancer. Lancet Oncol 2010; 11(12): 1172–1183.
48. Chun YS, Vauthey JN, Boonsirikamchai P et al. Association of computed tomography morphologic criteria with pathologic response and survival in patients treated with bevacizumab for colorectal liver metastases. JAMA 2009; 302(21): 2338–2344.
49. Miller JC, Pien HH, Sahani D et al. Imaging angiogenesis: applications and potential for drug development. J Natl Cancer Inst 2005; 97(3): 172–187.
50. O‘Connor JP, Jackson A, Asselin MC et al. Quantitative imaging biomarkers in the clinical development of targeted therapeutics current and future perspectives. Lancet Oncol 2008; 9(8): 766–776.
51. Nagengast WB, deVries EG, Hospers GA et al. In vivo VEGF imaging with radiolabeled bevacizumab in human ovarian tumor xenograft. J Nucl Med 2007; 48(8): 1313–1319.
52. Poon RT, Fan ST, Wong J. Clinical implications of circulating angiogenic factors in cancer patients. J Clin Oncol 2001; 19(4): 1207–1225.
53. Bernaards C, Hedge P, Chen D et al. Circulating vascular endothelial growth factor (VEGF) as a biomarker for bevacizumab-based therapy in metastatic colorectal, non-small cell lung, and renal cell cancer: analysis of pha-se III studies. J Clin Oncol 2010; 28 (Suppl): 15s, Abstract 10519.
54. Rüegg C, Meuwly JY, Driscol R et al. The quest for surrogate markers of angiogenesis: a paradigm for translational research in tumor angiogenesis and anti-angiogenesis trials. Curr Mol Med 2003; 3(8): 673–691.
55. Dowlati A, Gray R, Sandler AB et al. Cell adhesion molecules, vascular endothelial growth factor, and basic fibroblast growth factor in patients with non-small cell lung cancer treated with chemotherapy with or without bevacizumab: an Eastern Cooperative Oncology Study Group. Clin Cancer Res 2008; 14(5): 1407–1412.
56. Duda DG, Cohen KS, Ancukiewicz M et al. A comparative study of circulating endothelial cells (CECs) and circulating progenitor cells (CPCs) kinetics in four multidisciplinary phase II studies of antiangiogenic agents. J Clin Oncol 2008; 26 (Suppl): 15s, Abstract 3544.
57. Baar J, Silverman P, Lyons J et al. A vasculature-targeting regimen of preoperative docetaxel with or without bevacizumab for locally advanced breast cancer: impact on angiogenic biomarkers. Clin Cancer Res 2009; 15(10): 3583–3590.
58. Gao D, Nolan D, McDonnell K et al. Bone marrow-derived endothelial progenitor cells contribute to angiogenic switch in tumor growth and metastatic progression. Biochim Biophys Acta 2009; 1796(1): 33–40.
59. Schneider BP, Wang M, Radovich M et al. ECOG 2100. Association of vascular endothelial growth factor and vascular endothelial growth factor receptor-2 genetic polymorphisms with outcome in trial of paclitaxel plus bevacizumab in advanced breast cancer: ECOG 2100. J Clin Oncol 2008; 26(28): 4672–4678.
60. 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(22): 7554–7563.
61. Hlatky L, Hahnfeldt P, Folkma J. Clinical application of antiangiogenic therapy: microvessel density, what it does and doesn‘t tell us. J Natl Cancer Inst 2002; 94(12): 883–893.
62. Hurwitz H, Douglas PS, Middleton JP et al. Analysis of early hypertension (HTN) and clinical outcome with bevacizumab (BV). J Clin Oncol 2010; 28 (Suppl): 15s, abstr 3039.
63. Smith I. Goals of treatment for patients with metastatic breast cancer. Semin Oncol 2006; 33 (1 Suppl 2): S2–S5.
64. Sherrill B, Amonkar M, Wu Y et al. Relationship between effects of time-to-disease progression and overall survival in studies of metastatic breast cancer. Br J Cancer 2008; 99(10): 1572–1578.
65. Verma S, McLeod D, Batist G et al. In the end what matters most? A review of clinical endpoints in advanced breast cancer. The Oncologist 2011; 16(1): 25–35.
66. Broglio KR, Berry DA. Detecting an overall survival benefit that is derived from progression free survival. J Natl Cancer Inst 2009; 101(23): 1642–1649.
67. Alvarez RH, Guarneri V, Icli F et al. Bevacizumab treatment for advanced breast cancer. Oncologist 2011; 16(12): 1684–1697.
29. Miles DW, de Haas SL, Dirix L et al. Plasma biomarker analyses in the AVADO phase III randomized study of first-line bevacizumab plus docetaxel in patients with HER2-negative metastatic breast cancer. Cancer Res 2010; 70 (Suppl): 235s, Abstract P2-16-04.