Drugs

, Volume 70, Issue 2, pp 215–239

Trastuzumab

A Review of its Use as Adjuvant Treatment in Human Epidermal Growth Factor Receptor 2 (HER2) Positive Early Breast Cancer
  • Karly P. Garnock-Jones
  • Gillian M. Keating
  • Lesley J. Scott
Adis Drug Evaluation

Abstract

Trastuzumab (Herceptin®) is a humanized IgG1 κ monoclonal antibody, specifically targeted against the extracellular domain of the human epidermal growth factor receptor 2 (HER2), and is indicated for the treatment of HER2-positive early or metastatic breast cancer. This review discusses the available data regarding its use in early breast cancer.

Trastuzumab, when administered concurrently with chemotherapy regimens, consistently prolonged disease-free survival (primary endpoint) and overall survival (secondary endpoint) in patients with HER2-positive early breast cancer in well designed trials; studies evaluating sequential trastuzumab treatment have produced mixed results for these endpoints. Further study is required to ascertain the optimal trastuzumab treatment regimen, including the duration of treatment. Trastuzumab was generally well tolerated when added to, or administered following, a chemotherapy regimen in clinical trials. While cardiac adverse events, such as a decreased left ventricular ejection fraction and congestive heart failure, are a concern, these effects are treatable and appear to be mostly reversible. Thus, trastuzumab is a valuable component of treatment regimens for HER2-positive early breast cancer.

References

  1. 1.
    Benson JR, Jatoi I, Keisch M, et al. Early breast cancer. Lancet 2009 Apr 25; 373(9673): 1463–79PubMedCrossRefGoogle Scholar
  2. 2.
    Campbell JD, Ramsey SD. The costs of treating breast cancer in the US: a synthesis of published evidence. Pharmacoeconomics 2009; 27(3): 199–209PubMedCrossRefGoogle Scholar
  3. 3.
    National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: breast cancer [online]. Available from URL: http://www.nccn.org/professionals/physician_gls/PDF/breast.pdf [Accessed 2009 Jul 20]
  4. 4.
    Joy AA, Mackey JR. Adjuvant trastuzumab: progress, controversies, and the steps ahead. Curr Oncol 2006 Feb; 13(1): 8–13PubMedGoogle Scholar
  5. 5.
    Onitilo AA, Engel JM, Greenlee RT, et al. Breast cancer subtypes based on ER/PR and Her2 expression: comparison of clinicopathologic features and survival. Clin Med Res 2009 Jun; 7(1–2): 4–13PubMedGoogle Scholar
  6. 6.
    Carey LA, Perou CM, Livasy CA, et al. Race, breast cancer subtypes, and survival in the Carolina Breast Cancer Study. JAMA 2006 Jun 7; 295(21): 2492–502PubMedCrossRefGoogle Scholar
  7. 7.
    Spielmann M, Roche H, Delozier T, et al. Trastuzumab for patients with axillary-node-positive breast cancer: results of the FNCLCC-PACS 04 trial. J Clin Oncol 2009 Dec 20; 27(36): 6129–34PubMedCrossRefGoogle Scholar
  8. 8.
    Joensuu H, Kellokumpu-Lehtinen PL, Bono P, et al. Adjuvant docetaxel or vinorelbine with or without trastuzumab for breast cancer. N Engl J Med 2006 Feb 23; 354(8): 809–20PubMedCrossRefGoogle Scholar
  9. 9.
    McKeage K, Perry CM. Trastuzumab: a review of its use in the treatment of metastatic breast cancer overexpressing HER2. Drugs 2002; 62(1): 209–43PubMedCrossRefGoogle Scholar
  10. 10.
    Orman JS, Perry CM. Trastuzumab: in HER2 and hormone receptor co-positive metastatic breast cancer. Drugs 2007; 67(18): 2781–9PubMedCrossRefGoogle Scholar
  11. 11.
    Plosker GL, Keam SJ. Trastuzumab: a review of its use in the management of HER2-positive metastatic and early-stage breast cancer. Drugs 2006; 66(4): 449–75PubMedCrossRefGoogle Scholar
  12. 12.
    McKeage K, Lyseng-Williamson KA. Trastuzumab: a pharmacoeconomic review of its use in early breast cancer. Pharmacoeconomics 2008; 26(8): 699–719PubMedCrossRefGoogle Scholar
  13. 13.
    Valabrega G, Montemurro F, Aglietta M. Trastuzumab: mechanism of action, resistance and future perspectives in HER2-overexpressing breast cancer. Ann Oncol 2007 Jun; 18(6): 977–84PubMedCrossRefGoogle Scholar
  14. 14.
    Hudis CA. Trastuzumab: mechanism of action and use in clinical practice. N Engl J Med 2007 Jul 5; 357(1): 39–51PubMedCrossRefGoogle Scholar
  15. 15.
    Molina MA, Codony-Servat J, Albanell 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 Jun 15; 61(12): 4744–9PubMedGoogle Scholar
  16. 16.
    Lane HA, Motoyama AB, Beuvink I, et al. Modulation of p27/Cdk2 complex formation through 4D5-mediated inhibition of HER2 receptor signaling. Ann Oncol 2001; 12 Suppl. 1: S21–2PubMedCrossRefGoogle Scholar
  17. 17.
    Lane HA, Beuvink I, Motoyama AB, et al. ErbB2 potentiates breast tumor proliferation through modulation of p27(Kip1)-Cdk2 complex formation: receptor over-expression does not determine growth dependency. Mol Cell Biol 2000 May; 20(9): 3210–23PubMedCrossRefGoogle Scholar
  18. 18.
    Yakes FM, Chinratanalab W, Ritter CA, et al. Herceptin-induced inhibition of phosphatidylinositol-3 kinase and Akt is required for antibody-mediated effects on p27, cyclin D1, and antitumor action. Cancer Res 2002 Jul 15; 62(14): 4132–41PubMedGoogle Scholar
  19. 19.
    Junttila TT, Akita RW, Parsons K, et al. Ligand-independent HER2/HER3/PI3K complex is disrupted by trastuzumab and is effectively inhibited by the PI3K inhibitor GDC-0941. Cancer Cell 2009 May 5; 15(5): 429–40PubMedCrossRefGoogle Scholar
  20. 20.
    Fessler SP, Wotkowicz MT, Mahanta SK, et al. MUC1* is a determinant of trastuzumab (Herceptin) resistance in breast cancer cells. Breast Cancer Res Treat 2009 Nov; 118(1): 113–24PubMedCrossRefGoogle Scholar
  21. 21.
    Lu Y, Zi X, Pollak M. Molecular mechanisms underlying IGF-I-induced attenuation of the growth-inhibitory activity of trastuzumab (Herceptin) on SKBR3 breast cancer cells. Int J Cancer 2004 Jan 20; 108(3): 334–41PubMedCrossRefGoogle Scholar
  22. 22.
    Nagata Y, Lan KH, Zhou X, et al. PTEN activation contributes to tumor inhibition by trastuzumab, and loss of PTEN predicts trastuzumab resistance in patients. Cancer Cell 2004 Aug; 6(2): 117–27PubMedCrossRefGoogle Scholar
  23. 23.
    Nahta R, Takahashi T, Ueno NT, et al. P27(kip1) down-regulation is associated with trastuzumab resistance in breast cancer cells. Cancer Res 2004 Jun 1; 64(11): 3981–6PubMedCrossRefGoogle Scholar
  24. 24.
    Dokmanovic M, Hirsch DS, Shen Y, et al. Rac1 contributes to trastuzumab resistance of breast cancer cells: Rac1 as a potential therapeutic target for the treatment of trastuzumab-resistant breast cancer. Mol Cancer Ther 2009 Jun; 8(6): 1557–69PubMedCrossRefGoogle Scholar
  25. 25.
    Narayan M, Wilken JA, Harris LN, et al. Trastuzumab-induced HER reprogramming in “resistant” breast carcinoma cells. Cancer Res 2009 Mar 15; 69(6): 2191–4PubMedCrossRefGoogle Scholar
  26. 26.
    Shattuck DL, Miller JK, Carraway 3rd KL, et al. Met receptor contributes to trastuzumab resistance of Her2-overexpressing breast cancer cells. Cancer Res 2008 Mar 1; 68(5): 1471–7PubMedCrossRefGoogle Scholar
  27. 27.
    Nahta R, Yuan LX, Zhang B, et al. Insulin-like growth factor-I receptor/human epidermal growth factor receptor 2 hetero-dimerization contributes to trastuzumab resistance of breast cancer cells. Cancer Res 2005 Dec 1; 65(23): 11118–28PubMedCrossRefGoogle Scholar
  28. 28.
    Ropero S, Menendez JA, Vazquez-Martin A, et al. Trastuzumab plus tamoxifen: anti-proliferative and molecular interactions in breast carcinoma. Breast Cancer Res Treat 2004 Jul; 86(2): 125–37PubMedCrossRefGoogle Scholar
  29. 29.
    Nagy P, Friedlander E, Tanner M, et al. Decreased accessibility and lack of activation of ErbB2 in JIMT-1, a herceptin-resistant, MUC4-expressing breast cancer cell line. Cancer Res 2005 Jan 15; 65(2): 473–82PubMedGoogle Scholar
  30. 30.
    Valabrega G, Montemurro F, Sarotto I, et al. TGFa expression impairs trastuzumab-induced HER2 down-regulation. Oncogene 2005 Apr 21; 24(18): 3002–10PubMedCrossRefGoogle Scholar
  31. 31.
    Argiris A, Wang CX, Whalen SG, et al. Synergistic interactions between tamoxifen and trastuzumab (Herceptin). Clin Cancer Res 2004 Feb 15; 10(4): 1409–20PubMedCrossRefGoogle Scholar
  32. 32.
    Liang K, Lu Y, Jin W, et al. Sensitization of breast cancer cells to radiation by trastuzumab. Mol Cancer Ther 2003 Nov; 2(11): 1113–20PubMedGoogle Scholar
  33. 33.
    Pegram MD, Konecny GE, O’Callaghan C, et al. Rational combinations of trastuzumab with chemotherapeutic drugs used in the treatment of breast cancer. J Natl Cancer Inst 2004 May 19; 96(10): 739–49PubMedCrossRefGoogle Scholar
  34. 34.
    Pegram M, Hsu S, Lewis G, et al. Inhibitory effects of combinations of HER-2/neu antibody and chemotherapeutic agents used for treatment of human breast cancers. Oncogene 1999 Apr 1; 18(13): 2241–51PubMedCrossRefGoogle Scholar
  35. 35.
    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 HER 2. Clin Cancer Res 2004 Sep 1; 10(17): 5650–5PubMedCrossRefGoogle Scholar
  36. 36.
    Baselga J, Norton L, Albanell J, et al. Recombinant humanized anti-HER2 antibody (Herceptin) enhances the anti-tumor activity of paclitaxel and doxorubicin against HER2/neu overexpressing human breast cancer xenografts. Cancer Res 1998; 58: 2825–31PubMedGoogle Scholar
  37. 37.
    Fujimoto-Ouchi K, Sekiguchi F, Tanaka Y. Antitumor activity of combinations of anti-HER-2 antibody trastuzumab and oral fluoropyrimidines capecitabine/5′-dFUrd in human breast cancer models. Cancer Chemother Pharmacol 2002 Mar; 49(3): 211–6PubMedCrossRefGoogle Scholar
  38. 38.
    Izumi Y, Xu L, di Tomaso E, et al. Tumour biology: herceptin acts as an anti-angiogenic cocktail. Nature 2002; 416: 279–80PubMedCrossRefGoogle Scholar
  39. 39.
    Klos KS, Zhou X, Lee S, et al. Combined trastuzumab and paclitaxel treatment better inhibits ErbB-2-mediated angiogenesis in breast carcinoma through a more effective inhibition of Akt than either treatment alone. Cancer 2003 Oct 1; 98(7): 1377–85PubMedCrossRefGoogle Scholar
  40. 40.
    Clynes RA, Towers TL, Presta LG, et al. Inhibitory Fc receptors modulate in vivo cytoxicity against tumor targets. Nat Med 2000 Apr; 6(4): 443–6PubMedCrossRefGoogle Scholar
  41. 41.
    Mohsin SK, Weiss HL, Gutierrez MC, et al. Neoadjuvant trastuzumab induces apoptosis in primary breast cancers. J Clin Oncol 2005 Apr 10; 23(11): 2460–8PubMedCrossRefGoogle Scholar
  42. 42.
    Horton JK, Halle J, Ferraro M, et al. Radiosensitization of chemotherapy-refractory, locally advanced or locally recurrent breast cancer with trastuzumab: a phase II trial. Int J Radiat Oncol Biol Phys. Epub 2009 Jun 26Google Scholar
  43. 43.
    Genentech Inc. Herceptin® (trastuzumab) US prescribing information [online]. Available from URL: http://www.gene.com/gene/products/information/pdf/herceptin-prescribing.pdf [Accessed 2009 Jul 16]
  44. 44.
    European Medicines Agency. Herceptin® (trastuzumab): summary of product characteristics [online]. Available from URL: http://www.emea.europa.eu/humandocs/PDFs/EPAR/Herceptin/H-278-PI-en.pdf [Accessed 2009 Jul 16]
  45. 45.
    Baselga J, Carbonell X, Castaneda-Soto NJ, et al. Phase II study of efficacy, safety, and pharmacokinetics of trastuzumab monotherapy administered on a 3-weekly schedule. J Clin Oncol 2005 Apr 1; 23(10): 2162–71PubMedCrossRefGoogle Scholar
  46. 46.
    Leyland-Jones B, Gelmon K, Ayoub JP, et al. Pharmacokinetics, safety, and efficacy of trastuzumab administered every three weeks in combination with paclitaxel. J Clin Oncol 2003 Nov 1; 21(21): 3965–71PubMedCrossRefGoogle Scholar
  47. 47.
    Cobleigh MA, Vogel CL, Tripathy D, et al. Multinational study of the efficacy and safety of humanized anti-HER2 monoclonal antibody in women who have HER2-overexpressing metastatic breast cancer that has progressed after chemotherapy for metastatic disease. J Clin Oncol 1999 Sep; 17(9): 2639–48PubMedGoogle Scholar
  48. 48.
    Lunardi G, Vannozzi MO, Bighin C, et al. Influence of trastuzumab on epirubicin pharmacokinetics in metastatic breast cancer patients. Ann Oncol 2003 Aug; 14(8): 1222–6PubMedCrossRefGoogle Scholar
  49. 49.
    Nieto Y, Vredenburgh JJ, Shpall EJ, et al. Phase II feasibility and pharmacokinetic study of concurrent administration of trastuzumab and high-dose chemotherapy in advanced HER2+ breast cancer. Clin Cancer Res 2004 Nov 1; 10(21): 7136–43PubMedCrossRefGoogle Scholar
  50. 50.
    Czejka M, Ostermann E, Muric L, et al. Pharmacokinetics of gemcitabine combined with trastuzumab in patients with advanced breast cancer. Onkologie 2005 Jun; 28(6–7): 318–22PubMedCrossRefGoogle Scholar
  51. 51.
    Bruno R, Washington CB, Lu JF, et al. Population pharmacokinetics of trastuzumab in patients with HER2+ metastatic breast cancer. Cancer Chemother Pharmacol 2005 Oct; 56(4): 361–9PubMedCrossRefGoogle Scholar
  52. 52.
    Charoin J-E, Jacqmin P, Banken L, et al. Population pharmacokinetic analysis of trastuzumab (Herceptin) following long-term administration using different regimens [abstract no. 489 plus poster]. 13th Annual Meeting of the Population Approach Group in Europe; 2004 Jun 17–18; Uppsala [online]. Available from URL: http://www.page-meeting.org [Accessed 2009 Sep 09]
  53. 53.
    Piccart-Gebhart MJ, Procter M, Leyland-Jones B, et al. Trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer. N Engl J Med 2005 Oct 20; 353(16): 1659–72PubMedCrossRefGoogle Scholar
  54. 54.
    Romond EH, Perez EA, Bryant J, et al. Trastuzumab plus adjuvant chemotherapy for operable HER2-positive breast cancer. N Engl J Med 2005 Oct 20; 353(16): 1673–84PubMedCrossRefGoogle Scholar
  55. 55.
    Slamon D, Eiermann W, Robert N, et al. Phase III randomized trial comparing doxorubicin and cyclophosphamide followed by docetaxel (AC→T) with doxorubicin and cyclophosphamide followed by docetaxel and trastuzumab (AC→TH) with docetaxel, carboplatin and trastuzumab (TCH) in Her2neu positive early breast cancer patients: BCIRG 006 study [abstract no. 62 plus oral presentation]. 32nd Annual San Antonio Breast Cancer Symposium; 2009 Dec 9–13; San Antonio (TX)Google Scholar
  56. 56.
    Perez E, Suman V, Davidson N, et al. Further analysis of NCCTG-N9831 [oral presentation]. 41st Annual Meeting of the American Society of Clinical Oncology; 2005 May 13–17; Orlando (FL)Google Scholar
  57. 57.
    Perez E, Suman V, Davidson N, et al. Results of chemotherapy alone, with sequential or concurrent addition of 52 weeks of trastuzumab in the NCCTG N9831 HER2-positive adjuvant breast cancer trial [abstract no. 80 plus oral presentation]. 32nd San Antonio Breast Cancer Symposium; 2009 Dec 9–13; San Antonio (TX)Google Scholar
  58. 58.
    Slamon D, Eiermann W, Robert N, et al. BCIRG 006: 2nd interim analysis phase III randomized trial comparing doxorubicin and cyclophosphamide followed by docetaxel with doxorubicin and cyclophosphamide followed by docetaxel and trastuzumab with docetaxel, carboplatin and trastuzumab in Her2neu positive early breast cancer patients [abstract no. 52 plus oral presentation]. 29th Annual San Antonio Breast Cancer Symposium; 2006 Dec 14–16; San Antonio (TX)Google Scholar
  59. 59.
    Tan-Chiu E, Yothers G, Romond E, et al. Assessment of cardiac dysfunction in a randomized trial comparing doxorubicin and cyclophosphamide followed by paclitaxel, with or without trastuzumab as adjuvant therapy in node-positive, human epidermal growth factor receptor 2-over-expressing breast cancer: NSABP B-31. J Clin Oncol 2005 Nov 1; 23(31): 7811–9PubMedCrossRefGoogle Scholar
  60. 60.
    Smith I, Procter M, Gelber RD, et al. 2-year follow-up of trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer: a randomised controlled trial. Lancet 2007 Jan 6; 369(9555): 29–36PubMedCrossRefGoogle Scholar
  61. 61.
    Gianni L. Update of the HERA trial at 4 years’ median follow-up [oral presentation]. 1 1th International St Gallen Breast Cancer Conference; 2009 Mar 11–14; St GallenGoogle Scholar
  62. 62.
    Perez E, Romond E, Suman V, et al. Updated results of the combined analysis of NCCTG N9831 and NSABP B-31 adjuvant chemotherapy with/without trastuzumab in patients with HER2-positive breast cancer [abstract no. 512 plus oral presentation]. J Clin Oncol 2007 Jun; 25 (18S). 43rd Annual Meeting of the American Society of Clinical Oncology; 2007 Jun 1–5; Chicago (IL)Google Scholar
  63. 63.
    Slamon D, Eiermann W, Robert N, et al. Phase III randomized trial comparing doxorubicin and cyclophosphamide followed by docetaxel (AC→T) with doxorubicin and cyclophosphamide followed by docetaxel and trastuzumab (AC→TH) with docetaxel, carboplatin and trastuzumab (TCH) in HER2 positive early breast cancer patients: BCIRG 006 study [abstract no. 1 plus oral presentation]. 28th Annual San Antonio Breast Cancer Symposium; 2005 Dec 8–11; San Antonio (TX)Google Scholar
  64. 64.
    Au HJ, Robert N, Eiermann W, et al. BCIRG 006: quality of life of patients treated with docetaxel and trastuzumab-based regimens in node positive and high risk node negative HER2 positive early breast cancer [abstract no. 3063 plus poster]. Breast Cancer Res Treat 2007 Dec; 106 Suppl. 1: 147. 30th San Antonio Breast Cancer Symposium; 2007 Dec 13–16; San Antonio (TX)Google Scholar
  65. 65.
    Moreno-Aspitia A, Dueck AC, Lingle WL, et al. Serum HER2 levels in early-stage HER2 neu (+) breast cancer: results from the NCCTG adjuvant Intergroup trial N9831 [abstract no. 529]. 44th Annual Meeting of the American Society of Clinical Oncology 2008 May 30–Jun 3; Chicago (IL)Google Scholar
  66. 66.
    Untch M, Gelber RD, Jackisch C, et al. Estimating the magnitude of trastuzumab effects within patient subgroups in the HERA trial. Ann Oncol 2008 Jun; 19(6): 1090–6PubMedCrossRefGoogle Scholar
  67. 67.
    Dowsett M, Procter M, McCaskill-Stevens W, et al. Disease-free survival according to degree of HER2 amplification for patients treated with adjuvant chemotherapy with or without 1 year of trastuzumab: the HERA trial. J Clin Oncol 2009 Jun 20; 27(18): 2962–9PubMedCrossRefGoogle Scholar
  68. 68.
    Perez EA, Suman VJ, Davidson NE, et al. Cardiac safety analysis of doxorubicin and cyclophosphamide followed by paclitaxel with or without trastuzumab in the North Central Cancer Treatment Group N9831 adjuvant breast cancer trial. J Clin Oncol 2008 Mar 10; 26(8): 1231–8PubMedCrossRefGoogle Scholar
  69. 69.
    Suter TM, Procter M, van Veldhuisen DJ, et al. Trastuzumab-associated cardiac adverse effects in the herceptin adjuvant trial. J Clin Oncol 2007 Sep 1; 25(25): 3859–65PubMedCrossRefGoogle Scholar
  70. 70.
    Rastogi P, Jeong J, Geyer C, et al. Five year update of cardiac dysfunction on NSABP B-31, a randomized trial of sequential doxorubicin/cyclophosphamide (AC) → paclitaxel (T) vs. AC → T with trastuzumab (H) [abstract no. LBA513 plus oral presentation]. J Clin Oncol 2007; 25 (18S). 43rd annual meeting of the American Society of Clinical Oncology; 2007 Jun 1–5; Chicago (IL)Google Scholar
  71. 71.
    National Institute for Health and Clinical Excellence. Early and locally advanced breast cancer: diagnosis and treatment. NICE clinical guideline 80 [online]. Available from URL: http://www.nice.org.uk/nicemedia/pdf/CG80NICEGuideline.pdf [Accessed 2009 Jul 24]
  72. 72.
    Pharmaceutical Management Agency. Appendix Seven: relevant minutes of clinical advisory committees meetings since February 2007 [online]. Available from URL: http://www.pharmac.govt.nz/2008/08/07/TAR%2075c_%20Appendix%207%20to%20TAR%2075c%20-%20Minutes%20of%20clinical%20advisory%20committee%20meetings%20relevant%20to%20TAR75c.pdf [Accessed 2009 Sep 15]
  73. 73.
    Kurian AW, Thompson RN, Gaw AF, et al. A cost-effectiveness analysis of adjuvant trastuzumab regimens in early HER2/neu-positive breast cancer. J Clin Oncol 2007; 25(6): 634–41PubMedCrossRefGoogle Scholar
  74. 74.
    Jones AL, Barlow M, Barrett-Lee PJ, et al. Management of cardiac health in trastuzumab-treated patients with breast cancer: updated United Kingdom National Cancer Research Institute recommendations for monitoring. Br J Cancer 2009 Mar 10; 100(5): 684–92PubMedCrossRefGoogle Scholar
  75. 75.
    Joensuu H, Bono P, Kataja V, et al. Fluorouracil, epirubicin, and cyclophosphamide with either docetaxel or vinorelbine, with or without trastuzumab, as adjuvant treatments of breast cancer: final results of the FinHer Trial. J Clin Oncol 2009 Dec 1; 27(34): 5685–92PubMedCrossRefGoogle Scholar
  76. 76.
    National Cancer Institute. Trastuzumab in treating women with HER2-positive early breast cancer [ClinicalTrials.gov identifier NCT00712140]. US National Institutes of Health, ClinicalTrials.gov [online]. Available from URL: http://clinicaltrials.gov [Accessed 2009 Sep 21]
  77. 77.
    Finnish Breast Cancer Group. The synergism or long duration (SOLD) study [ClinicalTrials.gov identifier NCT00593697]. US National Institutes of Health, ClinicalTrials.gov [online]. Available from URL: http://clinicaltrials.gov [Accessed 2009 Sep 18]
  78. 78.
    Hellenic Oncology Research Group. Six vs 12 months of trastuzumab with docetaxel following FEC as adjuvant treatment in N+ breast cancer [ClinicalTrials.gov identifier NCT00615602]. US National Institutes of Health, Clinical Trials.gov [online]. Available from URL: http://clinicaltrials.gov [Accessed 2009 Sep 21]
  79. 79.
    Guarneri V, Frassoldati A, Bruzzi P, et al. Multicentric, randomized phase III trial of two different adjuvant chemotherapy regimens plus three versus twelve months of trastuzumab in patients with HER2-positive breast cancer (Short-HER Trial; NCT00629278). Clin Breast Cancer 2008 Oct; 8(5): 453–6PubMedCrossRefGoogle Scholar
  80. 80.
    National Cancer Institute. Trastuzumab for 6 months or 1 year in treating women with nonmetastatic breast cancer that can be removed by surgery [ClinicalTrials.gov identifier NCT00381901]. US National Institutes of Health, ClinicalTrials.gov [online]. Available from URL: http://clinicaltrials.gov [Accessed 2009 Nov 18]
  81. 81.
    Dedes KJ, Szucs TD, Imesch P, et al. Cost-effectiveness of trastuzumab in the adjuvant treatment of early breast cancer: a model-based analysis of the HERA and FinHer trial. Ann Oncol 2007 Sep; 18(9): 1493–9PubMedCrossRefGoogle Scholar
  82. 82.
    Neyt M, Huybrechts M, Hulstaert F, et al. Trastuzumab in early stage breast cancer: a cost-effectiveness analysis for Belgium. Health Policy 2008 Aug; 87(2): 146–59PubMedCrossRefGoogle Scholar
  83. 83.
    Gianni L, Semiglazov V, Manikhas G, et al. Neoadjuvant trastuzumab in locally advanced breast cancer (NOAH): antitumour and safety analysis [abstract no. 532]. J Clin Oncol 2007 Jun; 25 (18 Suppl., Part I of II) [online]. Available from URL: http://www.asco.org/ASCOv2/Meetings/Abstracts?&vmview=abst_detail_view&conID=47&abstractID=35265 [Accessed 2009 Sep 22]
  84. 84.
    Von Minckwitz G, Rezai M, Loibl P, et al. Effect of trastuzumab on pathologic complete response rate of neoadjuvant EC-docetaxel treatment in HER2-overexpressing breast cancer: results of the phase III GeparQuattro study [abstract no. 226]. 2008 American Society of Clinical Oncology Breast Cancer Symposium; 2008 Sep 5–7; Washington (DC) [online]. Available from URL: http://www.asco.org/ASCOv2/Meetings/Abstracts?&vmview=abst_detail_view&confID=58&abstractID=40260 [Accessed 2009 Sep 22]
  85. 85.
    Buzdar AU, Valero V, Ibrahim NK, et al. Neoadjuvant therapy with paclitaxel followed by 5-fluorouracil, epirubicin, and cyclophosphamide chemotherapy and concurrent trastuzumab in human epidermal growth factor receptor 2-positive operable breast cancer: an update of the initial randomized study population and data of additional patients treated with the same regimen. Clin Cancer Res 2007 Jan 1; 13(1): 228–33PubMedCrossRefGoogle Scholar

Copyright information

© Adis Data Information BV 2010

Authors and Affiliations

  • Karly P. Garnock-Jones
    • 1
  • Gillian M. Keating
    • 1
  • Lesley J. Scott
    • 1
  1. 1.Adis, a Wolters Kluwer BusinessMairangi Bay, North Shore, AucklandNew Zealand

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