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Targeted Therapy for Breast Cancer: A Focus on HER2/neu and Antiangiogenic Therapy

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From Local Invasion to Metastatic Cancer

Part of the book series: Current Clinical Oncology ((CCO))

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Abstract

Breast cancer is the most common female cancer in the USA and is the main cause of death in women aged 45–55 years. Despite advances in both diagnosis and treatment, an estimated 182,460 new cases (26% of all cancers) and 40,480 deaths are expected in 2008. One area of rapid evolution is the treatment of patients with HER2/neu overexpressing breast tumors, who comprise 25–30% of all breast cancers in the early stage setting. In conjunction with chemotherapy, trastuzumab has shown efficacy in both adjuvant and metastatic settings with improved response rate, time to progression, and overall survival. Lapatinib, a multitargeted tyrosine kinase inhibitor (TKI), is approved for trastuzumab-resistant disease in combination with capecitabine; multiple studies are evaluating lapatinib in combination with other chemotherapy agents as well as targeted biologic therapy. Additional anti-HER2/neu-targeted agents under study include immunotoxins, alternate antibodies, new TKIs, and new targeted therapies such as heat shock protein inhibitors. Antiangiogenic therapy is a second successful targeted biologic therapy for the treatment of breast cancer. Bevacizumab is now approved in combination with paclitaxel to treat advanced disease, and ongoing trials are investigating bevacizumab alone or in combination in both the early- and late-stage settings. Multiple other antiangiogenic agents are in clinical trials. This chapter will review current clinical data on HER2 and antiangiogenic biologic therapies in the treatment of breast cancer.

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References

  1. Jemal A, Siegel R, Ward E, et al.: Cancer statistics, 2008. CA Cancer J Clin 58:71–96, 2008

    Article  PubMed  Google Scholar 

  2. http://www.nccn.org/professionals/physician\_gls/PDF/breast.pdf, accessed December 10, 2007

    Google Scholar 

  3. Perou CM, Sorlie T, Eisen MB, et al.: Molecular portraits of human breast tumours. Nature 406:747–52, 2000

    Article  PubMed  CAS  Google Scholar 

  4. Sorlie T: Molecular portraits of breast cancer: tumour subtypes as distinct disease entities. Eur J Cancer 40:2667–75, 2004

    Article  PubMed  CAS  Google Scholar 

  5. Sorlie T, Wang Y, Xiao C, et al.: Distinct molecular mechanisms underlying clinically relevant subtypes of breast cancer: gene expression analyses across three different platforms. BMC Genomics 7:127, 2006

    Article  PubMed  Google Scholar 

  6. Esteva FJ, Hortobagyi GN: Prognostic molecular markers in early breast cancer. Breast Cancer Res 6:109–18, 2004

    Article  PubMed  CAS  Google Scholar 

  7. van’t Veer LJ, Dai H, van de Vijver MJ, et al.: Gene expression profiling predicts clinical outcome of breast cancer. Nature 415:530–6, 2002

    Article  Google Scholar 

  8. Slamon DJ, Clark GM, Wong SG, et al.: Human breast cancer: correlation of relapse and survival with amplification of the HER-2/neu oncogene. Science 235:177–82, 1987

    Article  PubMed  CAS  Google Scholar 

  9. Slamon DJ, Leyland-Jones B, Shak S, et al.: Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2. N Engl J Med 344:783–92, 2001

    Article  PubMed  CAS  Google Scholar 

  10. Romond EH, Perez EA, Bryant J, et al.: Trastuzumab plus adjuvant chemotherapy for operable HER2-positive breast cancer. N Engl J Med 353:1673–84, 2005

    Article  PubMed  CAS  Google Scholar 

  11. Fornier M, Esteva FJ, Seidman AD: Trastuzumab in combination with chemotherapy for the treatment of metastatic breast cancer. Semin Oncol 27:38–45, 2000

    PubMed  CAS  Google Scholar 

  12. Seidman AD, Fornier MN, Esteva FJ, et al.: Weekly trastuzumab and paclitaxel therapy for metastatic breast cancer with analysis of efficacy by HER2 immunophenotype and gene amplification. J Clin Oncol 19:2587–95, 2001

    PubMed  CAS  Google Scholar 

  13. Marty M, Cognetti F, Maraninchi D, et al.: Randomized phase II trial of the efficacy and safety of trastuzumab combined with docetaxel in patients with human epidermal growth factor receptor 2-positive metastatic breast cancer administered as first-line treatment: the M77001 study group. J Clin Oncol 23:4265–74, 2005

    Article  PubMed  CAS  Google Scholar 

  14. 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 20:719–26, 2002

    Article  PubMed  CAS  Google Scholar 

  15. Mackey JR, Kaufman B, Clemens M, et al.: Trastuzumab prolongs progression-free survival in hormone-dependent and HER2-positive metastatic breast cancer. Breast Cancer Res Treat 100(S1):3, 2006

    Google Scholar 

  16. Slamon D, Eiermann W, Robert N, et al.: BCIRG 006: 2nd interim analysis 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. Breast Cancer Res Treat 100(S1):52, 2006

    Google Scholar 

  17. Piccart-Gebhart MJ, Procter M, Leyland-Jones B, et al.: Trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer. N Engl J Med 353:1659–72, 2005

    Article  PubMed  CAS  Google Scholar 

  18. 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 369:29–36, 2007

    Article  PubMed  CAS  Google Scholar 

  19. Joensuu H, Kellokumpu-Lehtinen PL, Bono P, et al.: Adjuvant docetaxel or vinorelbine with or without trastuzumab for breast cancer. N Engl J Med 354:809–20, 2006

    Article  PubMed  CAS  Google Scholar 

  20. Gomez HL, Doval DC, Chavez MA, et al.: Efficacy and safety of lapatinib as first-line therapy for ErbB2-amplified locally advanced or metastatic breast cancer. J Clin Oncol 26:2999–3005, 2008

    Article  PubMed  CAS  Google Scholar 

  21. Burstein HJ, Storniolo AM, Franco S, et al.: A phase II study of lapatinib monotherapy in chemotherapy-refractory HER2-positive and HER2-negative advanced or metastatic breast cancer. Ann Oncol 19:1068–74, 2008

    Article  PubMed  CAS  Google Scholar 

  22. Geyer CE, Forster J, Lindquist D, et al.: Lapatinib plus capecitabine for HER2-positive advanced breast cancer. N Engl J Med 355:2733–43, 2006

    Article  PubMed  CAS  Google Scholar 

  23. Lin N, Dieras V, Paul D, et al.: EGF105084, a phase II study of lapatinib for brain metastases in patients (pts) with HER2+ breast cancer following trastuzumab (H) based systemic therapy and cranial radiotherapy (RT). J Clin Oncol 25(18S):1012, 2007

    Google Scholar 

  24. DiLeo A, Gomez H, Aziz Z, et al.: Lapatinib with paclitaxel versus paclitaxel as first-line treatment for patients with metastatic breast cancer: a phase III randomized, double-blind study in 580 patients. J Clin Oncol 25(18S):1011, 2007

    Google Scholar 

  25. O’Shaughnessy J, Blackwell KL, Burstein H, et al.: A randomized study of lapatinib alone or in combination with trastuzumab in heavily pretreated HER2+ metastatic breast cancer progressing on trastuzumab therapy. J Clin Oncol 26:1015, 2008

    Article  Google Scholar 

  26. Dang CT, Lin NU, Lake D, et al.: Preliminary safety results of dose-dense (dd) doxorubicin and cyclophosphamide (AC) followed by weekly paclitaxel (P) with trastuzumab (T) and lapatinib (L) in HER2 overexpressed/amplified breast cancer (BCA). J Clin Oncol 26:518, 2008

    Google Scholar 

  27. Burstein H, Awada A, Badwe R, et al.: HKI-272, an irreversible pan erbB receptor tyrosine kinase inhibitor: preliminary phase 2 results in patients with advanced breast cancer. Breast Cancer Res Treat 106:268, 2007

    Google Scholar 

  28. Krop IE, Beeram M, Modi S, et al.: A phase I study of tratuzumab DM-1, a first-in-class HER2 antibody drug-conjugate, in patients with advanced HER2+ breast cancer. . Breast Cancer Res Treat 106: 33, 2007

    Google Scholar 

  29. Solit DB, Rosen N: Hsp90: a novel target for cancer therapy. Curr Top Med Chem 6:1205–14, 2006

    Article  PubMed  CAS  Google Scholar 

  30. Solit DB, Ivy SP, Kopil C, et al.: Phase I trial of 17-allylamino-17-demethoxygeldanamycin in patients with advanced cancer. Clin Cancer Res 13:1775–82, 2007

    Article  PubMed  CAS  Google Scholar 

  31. Solit DB, Chiosis G: Development and application of Hsp90 inhibitors. Drug Discov Today 13:38–43, 2008

    Article  PubMed  CAS  Google Scholar 

  32. Modi S, Stopeck AT, Gordon MS, et al.: Combination of trastuzumab and tanespimycin (17-AAG, KOS-953) is safe and active in trastuzumab-refractory HER-2 overexpressing breast cancer: a phase I dose-escalation study. J Clin Oncol 25:5410–7, 2007

    Article  PubMed  CAS  Google Scholar 

  33. 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 10:1706–16, 2004

    Article  PubMed  CAS  Google Scholar 

  34. 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-amplified breast cancer. Breast Cancer Res Treat 100(S1):301, 2006

    Google Scholar 

  35. Rugo HS, Franco S, Munster P, et al.: A phase II evaluation of lapatinib (L) and bevacizumab (B) in HER2+ metastatic breast cancer (MBC). J Clin Oncol 26:1042, 2008

    Google Scholar 

  36. Slamon D, Gomez HL, Kabbinawar FFA, et al.: Randomized study of pazopanib + lapatinib vs. lapatinib alone in patients with HER2- positive advanced or metastatic breast cancer. J Clin Oncol 26:1016, 2008

    Article  Google Scholar 

  37. Cobleigh MA, Langmuir VK, Sledge GW, et al.: A phase I/II dose-escalation trial of bevacizumab in previously treated metastatic breast cancer. Semin Oncol 30:117–24, 2003

    Article  PubMed  CAS  Google Scholar 

  38. 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 23:792–9, 2005

    Article  PubMed  CAS  Google Scholar 

  39. Miller K, Wang M, Gralow J, et al.: Paclitaxel plus bevacizumab versus paclitaxel alone for metastatic breast cancer. N Engl J Med 357:2666–76, 2007

    Article  PubMed  CAS  Google Scholar 

  40. Burstein HJ, Elias AD, Rugo HS, et al.: Phase II study of sunitinib malate, an oral multitargeted tyrosine kinase inhibitor, in patients with metastatic breast cancer previously treated with an anthracycline and a taxane. J Clin Oncol 26:1810–16, 2008

    Article  PubMed  CAS  Google Scholar 

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© 2009 Humana Press, a part of Springer Science+Business Media, LLC

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Rugo, H.S., Lin, A.YJ. (2009). Targeted Therapy for Breast Cancer: A Focus on HER2/neu and Antiangiogenic Therapy. In: Leong, S. (eds) From Local Invasion to Metastatic Cancer. Current Clinical Oncology. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-60327-087-8_42

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  • DOI: https://doi.org/10.1007/978-1-60327-087-8_42

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  • Publisher Name: Humana Press, Totowa, NJ

  • Print ISBN: 978-1-60327-086-1

  • Online ISBN: 978-1-60327-087-8

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