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BioDrugs

, Volume 21, Issue 2, pp 69–77 | Cite as

HER-2-Positive Breast Cancer

Hope Beyond Trastuzumab
  • Rupert Bartsch
  • Catharina Wenzel
  • Christoph C. Zielinski
  • Guenther G. Steger
Current Opinion

Abstract

Therapeutic antibodies have shown great promise as targeted agents in the treatment of patients with cancer. Trastuzumab, a humanized monoclonal antibody targeting human epidermal growth factor receptor-2 (HER-2), is of special importance in breast cancers overexpressing HER-2. Such rationally designed substances bind to cancer cells expressing the targeted antigen and, by various mechanisms, lead to tumor cell degradation. Only one-third of patients, however, initially respond to trastuzumab monotherapy and the majority of initial responders demonstrate disease progression within 1 year of treatment initiation. Therefore, alternative compounds targeting the HER-2 receptor or downstream signaling pathways are of great importance.

Lapatinib is a tyrosine kinase inhibitor, blocking tryosine kinase domains of both epidermal growth factor receptor and HER-2. This substance holds promise for the treatment of cancer after trastuzumab failure, and might be active in cerebral metastases. Other strategies in trastuzumab-resistant disease include bispecific antibodies (which bind to HER-2 and Fc receptors, thereby directing immune cells towards the tumor), the combination of antibodies, or targeting tumor vessel growth by blocking vascular endothelial growth factor (VEGF) or VEGF receptors. Heat shock protein 90, a chaperone protein that controls the folding of HER-2, also represents a potential target. Multi-targeted kinase inhibitors such as sunitinib or sortenib are already established in renal cell cancer. These compounds are currently being evaluated in breast cancer and might represent interesting options both in HER-2-positive and -negative disease.

In conclusion, trastuzumab remains the gold standard in HER-2-positive breast cancer therapy. However, in trastuzumab-resistant disease, new strategies and compounds are currently under evaluation.

Keywords

Breast Cancer Vascular Endothelial Growth Factor Bevacizumab Trastuzumab Brain Metastasis 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Acknowledgments

The authors have no conflicts of interest that are directly relevant to the content of this review article. No sources of funding were used to assist in the preparation of this review.

References

  1. 1.
    Faneyte IF, Peterse JL, Van Tinteren H, et al. Predicting early failure after adjuvant chemotherapy in high-risk breast cancer patients with extensive lymph node involvement. Clin Cancer Res 2004; 10: 4457–63PubMedCrossRefGoogle Scholar
  2. 2.
    Beslija S, Bonneterre J, Burstein H, et al. Second consensus on medical treatment of metastatic breast cancer. Ann Oncol 2007 Feb; 18(2): 215–25PubMedCrossRefGoogle Scholar
  3. 3.
    van’t Veer LJ, Dai H, van de Vijver MJ, et al. Gene expression profiling predicts clinical outcome of breast cancer. Nature 2002; 415: 530–6CrossRefGoogle Scholar
  4. 4.
    van de Vijver MJ, He YD, van’t Veer LJ, et al. A gene-expression signature as a predictor of survival in breast cancer. N Engl J Med 2002; 347: 1999–2009PubMedCrossRefGoogle Scholar
  5. 5.
    Slamon DJ, Clark GM, Wong SG, et al. Human breast cancer: correlation of relapse and survival with amplification of the HER2/neu oncogene. Science 1987; 235: 177–82PubMedCrossRefGoogle Scholar
  6. 6.
    Boss JS, Fletcher JA, Linette GP. The HER-2/neu gene and protein in breast cancer 2003: biomarker and target of therapy. Oncologist 2003; 8: 307–25CrossRefGoogle Scholar
  7. 7.
    Paik S, Hazan R, Fisher ER, et al. Pathologic finding from the National Surgical Adjuvant Breast and Bowel Project: prognostic significance of erbB-2 protein expression in primary breast cancer. J Clin Oncol 1990; 8: 103–12PubMedGoogle Scholar
  8. 8.
    Kallioniemi OP, Holli K, Visakorpi T, et al. Association of c-erbB-2 protein over-expression with high rate of cell proliferation, increased risk of visceral metastasis and poor long-term survival in breast cancer. Int J Cancer 1991; 4: 650–5CrossRefGoogle Scholar
  9. 9.
    Akiyama T, Saito T, Ogawara H, et al. Tumor promoter and epidermal growth factor stimulate phosphorylation of the c-erbB-2 gene product in MKN-7 human adenocarcinoma cells. Mol Cell Biol 1988; 8: 1019–26PubMedGoogle Scholar
  10. 10.
    Bargmann CI, Hung MC, Weinberg RA. The neu oncogene encodes an epidermal growth factor receptor-related protein. Nature 1986; 319: 226–30PubMedCrossRefGoogle Scholar
  11. 11.
    Pegram MD, Reese DM. Combined biological therapy of breast cancer using monoclonal antibodies directed against HER2/neu protein and vascular endothelial growth factor. Semin Oncol 2002 Jun; 29Suppl. 11: 29–37PubMedGoogle Scholar
  12. 12.
    Schiff R, Massarweh SA, Shou J, et al. Cross-talk between estrogen receptor and growth factor pathways as a molecular target for overcoming endocrine resistance. Clin Cancer Res 2004; 10: 331S–6SPubMedCrossRefGoogle Scholar
  13. 13.
    Casalini P, Iorio MV, Galmozzi E, et al. Role of HER receptors family in development and differentiation. J Cell Physiol 2004; 200: 343–50PubMedCrossRefGoogle Scholar
  14. 14.
    Fukazawa R, Miller TA, Kuramochi Y, et al. Neuregulin-1 protects ventricular myocytes from anthracycline-induced apoptosis via erbB4-dependent activation of PI3-kinase/Akt. J Mol Cell Cardiol 2003; 35: 1473–9PubMedCrossRefGoogle Scholar
  15. 15.
    Nahta R, Yu D, Hung MC, et al. Mechanisms of disease: understanding resistance to Her2-targeted therapy in human breast cancer. Nat Clin Pract Oncol 2006; 3: 269–80PubMedCrossRefGoogle Scholar
  16. 16.
    Molina MA, Codony-Servat J, Albaneil J, et al. Trastuzumab (Herceptin), a humanized anti-HER2 receptor monoclonal antibody, inhibits basal and activated HER2 ectodomain cleavage in breast cancer cells. Cancer Res 2001; 61: 4744–9PubMedGoogle Scholar
  17. 17.
    Clynes RA, Towers TL, Presta LG, et al. Inhibitory Fc receptors modulate in vivo cytotoxicity against tumor targets. Nat Med 2000 Apr; 6(4): 443–6PubMedCrossRefGoogle Scholar
  18. 18.
    Gennari R, Menard S, Fagnoni F, et al. Pilot study of the mechanism of action of preoperative trastuzumab in patients with primary operable breast tumors overexpressing HER2. Clin Cancer Res 2004; 10: 5650–5PubMedCrossRefGoogle Scholar
  19. 19.
    Cooley S, Burns LJ, Repka T, et al. Natural killer cell cytotoxicity of breast cancer targets is enhanced by two distinct mechanisms of antibody dependent cellular cytotoxicity against LFA-3 and HER2/neu. Exp Hematol 1999; 27: 1533–41PubMedCrossRefGoogle Scholar
  20. 20.
    Cuello M, Ettenberg SA, Clark AS, et al. Down-regulation of the erbB-2 receptor by trastuzumab (Herceptin) enhances tumor necrosis factor-related apoptosis-inducing ligand-mediated apoptosis in breast and ovarian cancer cell lines that overexpress erbB-2. Cancer Res 2001; 61: 4892–900PubMedGoogle Scholar
  21. 21.
    Lane HA, Motoyama AB, Beuvink I, et al. Modulation of p27/Cdk2 complex formation through 4D5-mediated inhibition of HER2 receptor signalling. Ann Oncol 2001; 12Suppl. 1: 21S–2SCrossRefGoogle Scholar
  22. 22.
    Yakes FM, Chinratanalab W, Ritter CA, et al. Herceptin-induced inhibition of phophatidylinositol–3 kinase and Akt is required for antibody-mediated effects on p27, cyclin D1, and antitumor action. Cancer Res 2002; 62: 4132–41PubMedGoogle Scholar
  23. 23.
    Pietras RJ, Fendly BM, Chazin VR, et al. Antibody to HER-2/neu receptor blocks DNA repair after cisplatin in human breast and ovarian cancer cells. Oncogene 1994; 9: 1829–38PubMedGoogle Scholar
  24. 24.
    Pietras RJ, Pegram MD, Finn RS, et al. Remission of human breast cancer xenografts on therapy with humanized monoclonal antibody to HER-2 receptor and DNA-reactive drugs. Oncogene 1998; 17: 2235–49PubMedCrossRefGoogle Scholar
  25. 25.
    Pietras RJ, Poen JC, Gallardo D, et al. Monoclonal antibody to HER-2/neu receptor modulates repair of radiation-induced DNA damage and enhance radiosensitivity of human breast cancer cell overexpressing this oncogene. Cancer Res 1999; 59: 1347–55PubMedGoogle Scholar
  26. 26.
    Miller KD, Chap LI, Holmes FA, et al. Randomized phase III trial of capecitabine compared with bevacizumab and capecitabine in patients with previously treated metastatic breast cancer. J Clin Oncol 2005; 23: 792–9PubMedCrossRefGoogle Scholar
  27. 27.
    Zon R, Miller K, Wang M, et al. A randomized phase III trial of paclitaxel with or without bevacizumab as first-line therapy for locally recurrent or metastatic breast cancer: Eastern Cooperative Oncology Group trial E2100 [abstract]. Eur J Cancer Suppl 2006; 4(2): 47CrossRefGoogle Scholar
  28. 28.
    Harris M, Smith I. The development and clinical use of trastuzumab (Herceptin). Endocrine Related Cancer 2002; 9: 75–85CrossRefGoogle Scholar
  29. 29.
    Slamon DJ, Leyland-Jones B, Shak S, et al. Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overex-presses HER2. N Engl J Med 2001; 344: 783–92PubMedCrossRefGoogle Scholar
  30. 30.
    Piccart-Gebhart MJ, Proctet M, Leyland-Jones B, et al. Trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer. N Engl J Med 2005; 353: 1659–72PubMedCrossRefGoogle Scholar
  31. 31.
    Romond EH, Perez EA, Bryant J, et al. Trastuzumab plus adjuvant chemotherapy for operable HER2-positive breast cancer. N Engl J Med 2005; 353: 1673–84PubMedCrossRefGoogle Scholar
  32. 32.
    Kaufman B, Mackey J, Clemens M, et al. Trastuzumab plus anastrozole prolongs progression-free survival in postmenopausal women with HER2-positive, hormone-dependent metastatic breast cancer (MBC). Ann Oncol 2006; 17Suppl. 9: 24Google Scholar
  33. 33.
    Vogel CL, Cobleigh MA, Tripathy D, et al. Efficacy and safety of trastuzumab as a single agent in first-line treatment of HER2-overexpressing metastatic breast cancer. J Clin Oncol 2002; 20: 719–26PubMedCrossRefGoogle Scholar
  34. 34.
    Fountzilas G, Razis E, Tsavdaridis D, et al. Continuation of trastuzumab beyond disease progression is feasible and safe in patients with metastatic breast cancer: a retrospective analysis of 80 cases by the Hellenic cooperative oncology group. Clin Breast Cancer 2003; 4: 120–5PubMedCrossRefGoogle Scholar
  35. 35.
    Tripathy D, Slamon D, Cobleigh M, et al. Safety of treatment of metastatic breast cancer with trastuzumab beyond disease progression. J Clin Oncol 2004; 6: 1063–70CrossRefGoogle Scholar
  36. 36.
    Bartsch R, Wenzel C, Hussian D, et al. Analysis of trastuzumab and chemotherapy in advanced breast cancer after the failure of at least one earlier combination: an observational study. BMC Cancer 2006; 6: 63PubMedCrossRefGoogle Scholar
  37. 37.
    Esparis-Ogando A, Diaz-Rodriguez E, Pandiella A. Signalling-competent truncated forms of ErbB2 in breast cancer cells: differential regulation by protein kinase C and phosphatidylinositol 3-kinase. Biochem J 1999; 344: 339–48PubMedCrossRefGoogle Scholar
  38. 38.
    Bendell JC, Domchek SM, Burstein HJ, et al. Central nervous system metastases in women who receive trastuzumab-based therapy for metastatic breast carcinoma. Cancer 2003; 97: 2972–7PubMedCrossRefGoogle Scholar
  39. 39.
    Shmueli E, Wigler N, Inbar M. Central nervous system progression among patients with metastatic breast cancer responding to trastuzumab treatment. Eur J Cancer 2004; 40: 379–82PubMedCrossRefGoogle Scholar
  40. 40.
    Clayton AJ, Danson S, Jolly S, et al. Incidence of cerebral metastases in patients treated with trastuzumab for metastatic breast cancer. Br J Cancer 2004; 91: 639–43PubMedGoogle Scholar
  41. 41.
    Bartsch R, Fromm S, Rudas M, et al. Intensified local treatment and systemic therapy significantly increase survival in patients with brain metastases from advanced breast cancer: a retrospective analysis. Radiother Oncol 2006; 80: 313–7PubMedCrossRefGoogle Scholar
  42. 42.
    Rosner D, Nemoto T, Lane WW. Chemotherapy induces regression of brain metastases in breast carcinoma. Cancer 1986; 58: 832–9PubMedCrossRefGoogle Scholar
  43. 43.
    Boogerd W, Dalesio O, Bais EM, et al. Response of brain metastases from breast cancer to systemic chemotherapy. Cancer 1992; 69: 972–80PubMedCrossRefGoogle Scholar
  44. 44.
    Rugo HS. Bevacizumab in the treatment of breast cancer: rationale and current data. Oncologist 2004; 9Suppl. 1: 43–9PubMedCrossRefGoogle Scholar
  45. 45.
    Agus DB, Gordon MS, Taylor C, et al. Phase I clinical study of pertuzumab, a novel HER dimerization onhibitor, in patients with advanced cancer. J Clin Oncol 2005; 23: 2534–43PubMedCrossRefGoogle Scholar
  46. 46.
    King CR, Fischer PH, Rando RF, et al. The performance of e23(Fv)PEs, recombinant toxins targeting the erbB-2 protein. Semin Cancer Biol 1996; 7: 79–86PubMedCrossRefGoogle Scholar
  47. 47.
    Reiter Y, Kreitman RJ, Brinkmann U, et al. Cytotoxic and antitumor activity of a recombinant immunotoxin composed of disulfide-stabilized anti-Tac Fv fragment and truncated Pseudomonas exotoxin. Int J Cancer 1994; 58: 142–9PubMedCrossRefGoogle Scholar
  48. 48.
    Kiewe P, Hasmuller S, Kahlert S, et al. Phase I trial of the trifunctional anti-Her2 x anti-CD3 antibody ertumoxomab in metastatic breast cancer. Clin Cancer Res 2006; 12: 3085–91PubMedCrossRefGoogle Scholar
  49. 49.
    Konecny GE, 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: 1706–16PubMedCrossRefGoogle Scholar
  50. 50.
    Pegram M, Chan D, Dichmann RA, et al. 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-am-plified breast cancer. Breast Cancer Res Treat 2006; 100 (1 Suppl.): 28SGoogle Scholar
  51. 51.
    Storniolo AM, Burris H, Pegram M, et al. A phase I, open-label study of lapatinib (GW572016) plus trastuzumab; a clinically active regimen. J Clin Oncol 2005; 23 (16 Suppl.): 18SGoogle Scholar
  52. 52.
    Strumberg D, Richly H, Hilger RA, et al. Phase I clinical and pharmacokinetic study of the Novel Raf kinase and vascular endothelial growth factor receptor inhibitor BAY 43-9006 in patients with advanced refractory solid tumors. J Clin Oncol 2005; 23: 965–72PubMedCrossRefGoogle Scholar
  53. 53.
    Deprimo SE, Friece C, Huang J, et al. Effect of treatment with sunitinib malate, a multitargeted tyrosine kinase inhibitor, on circulating plasma levels of VEGF, soluble VEGF receptors 2 and 3, and soluble KIT in patients with metastatic breast cancer. J Clin Oncol 2006; 24 (18 Suppl.): 23SCrossRefGoogle Scholar
  54. 54.
    Knutson KL, Schiffman K, Cheever MA, et al. Immunization of cancer patients with a Her-2/neu, HLA-A3 peptide, p369-377, results in short-lived peptide-specific immunity. Clin Cancer Res 2002; 8: 1014–8PubMedGoogle Scholar
  55. 55.
    Zhang H, Burrows F. Targeting multiple signal transduction pathways through inhibition of Hsp90. J Mol Med 2004; 82: 488–99PubMedGoogle Scholar
  56. 56.
    Hughes TP, Kaeda J, Branford S, et al. International Randomised Study of Interferon versus STI571 (IRIS) Study Group. Frequency of major molecular responses to imatinib or interferon alfa plus cytarabine in newly diagnosed chronic myeloid leukemia. N Engl J Med 2003; 349: 1423–32PubMedCrossRefGoogle Scholar
  57. 57.
    Shepherd FA, Pereira JR, Ciuleanu T, et al. for the National Cancer Institute of Canada Clinical Trials Group. Erlotinib in previously treated non-small-cell lung cancer. N Engl J Med 2005; 353: 123–32PubMedCrossRefGoogle Scholar
  58. 58.
    Janne PA, Johnson BE. Effect of epidermal growth factor receptor tyrosine kinase domain mutations on the outcome of patients with non-small cell lung cancer treated with epidermal growth factor receptor tyrosine kinase inhibitors. Clin Cancer Res 2006; 12: 4416S–20SPubMedCrossRefGoogle Scholar
  59. 59.
    Dowsett M, Smith I, Skene A, et al. on behalf of the Study 0223 Trialists. Biological and clinical outcomes from a phase II placebo-controlled neoadjuvant study of anastrozole alone or with gefitinib in postmenopausal women with ER/PgR+ breast cancer (Study 223). J Clin Oncol 2006; 24 (18 Suppl.): 6SGoogle Scholar
  60. 60.
    Escudier B, Szczylik C, Demkow T, et al. Randomized phase II trial of the multi-kinase inhibitor sorafenib versus interferon (IFN) in treatment-naive patients with metastatic renal cell carcinoma (mRCC). J Clin Oncol 2006; 24 (18 Suppl.): 217SGoogle Scholar
  61. 61.
    Ryan CW, Goldman BH, Lara PN Jr, et al. Sorafenib plus interferon-α2b (INF) as first-line therapy for advanced renal cell carcinoma (RCC): SWOG 0412. J Clin Oncol 2006; 24 (18 Suppl.): 223SGoogle Scholar
  62. 62.
    Ratain MJ, Eisen T, Stadler WM, et al. Phase II placebo-controlled randomized discontinuation trial of sorafenib in patients with metastatic renal cell carcinoma. J Clin Oncol 2006; 24: 2505–12PubMedCrossRefGoogle Scholar
  63. 63.
    Motzer RJ, Hutson TE, Tomczak P, et al. Phase II randomized trial of sunitinib malate (SU11248) versus interferon-alfa (INF-α) as first-line systemic therapy for patients with metastatic renal cell carcinoma (mRCC). J Clin Oncol 2006; 24 (18 Suppl.): 930SGoogle Scholar
  64. 64.
    Xia W, Bisi J, Strum J, et al. Regulation of survivin by ErbB2 signaling: therapeutic implications for ErbB2-overexpressing breast cancers. Cancer Res 2006; 66: 1640–7PubMedCrossRefGoogle Scholar
  65. 65.
    Konecny GE, Pegram MD, Venkatesan N, et al. Activity of the dual kinase inhibitor lapatinib (GW572016) against HER-2-overexpressing and tras-tuzumab-treated breast cancer cells. Cancer Res 2006; 66: 1630–9PubMedCrossRefGoogle Scholar
  66. 66.
    Lin NU, Carey LA, Liu MC, et al. Phase II trial of lapatinib for brain metastases in patients with Her2+ breast cancer. J Clin Oncol 2006; 24 (18 Suppl.): 503SCrossRefGoogle Scholar
  67. 67.
    Cameron DA, Geyer CE, Chan DS, et al. Lapatinib in combination with capecitabine demonstrates superior efficacy compared with capecitabine alone in erbb3+ advanced or metastatic breast cancer (MBC) patients (pts) pretreated with chemotherapy and trastuzumab. Ann Oncol 2006; 17Suppl. 9: 69Google Scholar
  68. 68.
    ClinicalTrials.gov. Letrozole in combination with lapatinib in neoadjuvant treatment of early breast cancer [online]. Available from URL: http://clinicaltrials.gov/ct/show/NCT00422903?.order=1 [Accessed 2007 Feb 26]
  69. 69.
    ClinicalTrials.gov. ErbB2 over-expressing metastatic breast cancer study using paclitaxel, trastuzumab, and lapatinib [online]. Available from URL: http://clinicaltrials.gov/ct/show/NCT00272987?.order=1 [Accessed 2007 Feb 26]
  70. 70.
    GlaxoSmithKline. Tykerb evaluation after chemotherapy (TEACH): lapatinib versus placebo in women with early-stage breast cancer. ClinicalTrials.gov no. NCT00374322 [online]. Available from URL: http://clinicaltrials.gov/ct/show/NCT00374322?order=4 [Accessed 2007 Mar 14]
  71. 71.
    Lenz HJ. Anti-EGFR mechanism of action: antitumor effect and underlying cause of adverse events. Oncology 2006; 20Suppl. 2: 5–13PubMedGoogle Scholar
  72. 72.
    Cunningham D, Humblet Y, Siena S, et al. Cetuximab monotherapy and cetuximab plus irinotecan in irinotecan-refractory metastatic colorectal cancer. N Engl J Med 2004; 351: 337–45PubMedCrossRefGoogle Scholar
  73. 73.
    Bonner JA, Harari PM, Giralt J, et al. Radiotherapy plus cetuximab for squamous-cell carcinoma of the head and neck. N Engl J Med 2006; 354: 567–78PubMedCrossRefGoogle Scholar
  74. 74.
    Kelly H, Goldberg RM. Systemic therapy for metastatic colorectal cancer: current options, current evidence. J Clin Oncol 2005; 23: 4553–60PubMedCrossRefGoogle Scholar
  75. 75.
    Yen L, You XL, Al Moustafa AE, et al. Heregulin selectively upregulates vascular endothelial growth factor secretion in cancer cell and stimulates angiogenesis. Oncogene 2000; 19: 3460–9PubMedCrossRefGoogle Scholar
  76. 76.
    Izumi Y, Xu L, di Tomaso E, et al. Tumour biology: herceptin acts as an anti-angiogenic cocktail. Nature 2002; 416: 279–80PubMedCrossRefGoogle Scholar
  77. 77.
    Laughner E, Taghavi P, Chiles K, et al. HER2 (neu) signaling increases the rate hypoxia-induceable factor la (HIF-1α) synthesis: novel mechanism for HIF-1-mediated vascular endothelial growth factor expression. Mol Cell Biol 2001; 21: 3995–4004PubMedCrossRefGoogle Scholar
  78. 78.
    ClinicalTrials.gov. Pilot study of safety and efficacy of three docetaxel-based chemotherapy regimens plus bevacizumab ± trastuzumab for adjuvant treatment of patients with node-positive and high-risk node-negative breast cancer [online]. Available from URL: httpV/clinicaltrials.gov/ct/show/NCT00365365?.order=4 [Accessed 2007 Feb 26]
  79. 79.
    Cho HS, Mason K, Ramyar KX, et al. Structure of the extracellular region of HER2 alone and in complex with the herceptin Fab. Nature 2003; 421: 756–60PubMedCrossRefGoogle Scholar
  80. 80.
    Fendly BM, Winget M, Hudziak RM, et al. Characterization of murine monoclonal antibodies reactive to either the human epidermal growth factor receptor or HER2/neu gene product. Cancer Res 1990; 50: 1550–8PubMedGoogle Scholar
  81. 81.
    Agus DB, Akita RW, Fox WD, et al. Targeting ligand-activated ErbB2 signaling inhibits breast and prostate tumor growth. Cancer Cell 2002; 2: 127–37PubMedCrossRefGoogle Scholar
  82. 82.
    Human DW, Wiesenfeld M, Hobday TJ, et al. Bay 43-9006 as single oral agent in patients with metatstatic breast cancer previously exposed to anthracycline and/or taxane. J Clin Oncol 2006; 24 (18 Suppl.): 22SGoogle Scholar
  83. 83.
    Miller KD, Burstein HJ, Elias AD, et al. Phase II study of SU11248, a multitargeted tyrosine kinase inhibitor (TKI), in patients (pts) with previously treated meta-static breast cancer (MBC). J Clin Oncol 2005; 23 (16 Suppl.): 19SGoogle Scholar

Copyright information

© Adis Data Information BV 2007

Authors and Affiliations

  • Rupert Bartsch
    • 1
  • Catharina Wenzel
    • 1
  • Christoph C. Zielinski
    • 1
  • Guenther G. Steger
    • 1
  1. 1.Department of Medicine 1 and Cancer Center, Clinical Division of OncologyMedical University of ViennaViennaAustria

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