Skip to main content
SpringerLink
Log in

Targeted Therapies for HER2-positive Breast Cancer

  • Chapter
  • First Online:
Targeted Therapies for Solid Tumors

Part of the book series: Current Clinical Pathology ((CCPATH))

  • 1161 Accesses

Abstract

Breast cancer is a heterogeneous disease, encompassing at least three different tumor subtypes: the hormone receptor-positive, the HER2-positive and the triple negative disease. In the last decades, the introduction of the monoclonal antibody trastuzumab for the treatment of both early and advanced HER2-positive diseases has substantially reverted the poor prognostic implications driven by HER2 overexpression/amplification. Following trastuzumab, other effective targeted drugs have received approval for the treatment of this breast cancer subtype. However, despite these advances, resistance to such therapies finally occurs, resulting in disease progression. Recently, a deeper knowledge of HER2 biology has translated into the development of novel anti-HER2 agents with different mechanisms of action. Interestingly, some recent data highlight the possibility of effectively combining different targeted agents together without the addition of chemotherapy. In this chapter, we will review the state of the art on the already approved anti-HER2 agents, novel compounds in the phases of clinical development and ongoing trials.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 59.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 79.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 109.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Arteaga CL, Sliwkowski MX, Osborne CK, Perez EA, Puglisi F, Gianni L. Treatment of HER2-positive breast cancer: current status and future perspectives. Nat Rev Clin Oncol. 2012;9:16–32.

    Article  CAS  Google Scholar 

  2. Cobleigh MA, Vogel CL, Tripathy D, Robert NJ, Scholl S, Fehrenbacher L, Wolter JM, Paton V, Shak S, Lieberman G, Slamon DJ. 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;17(9):2639–48.

    CAS  PubMed  Google Scholar 

  3. Baselga J, Tripathy D, Mendelsohn J, Baughman S, Benz CC, Dantis L, Sklarin NT, Seidman AD, Hudis CA, Moore J, Rosen PP, Twaddell T, Henderson IC, Norton L. Phase II study of weekly intravenous recombinant humanized anti-p185HER2 monoclonal antibody in patients with HER2/neu-overexpressing metastatic breast cancer. J Clin Oncol. 1996;14(3):737–44.

    CAS  PubMed  Google Scholar 

  4. Vogel CL, Cobleigh MA, Tripathy D, Gutheil JC, Harris LN, Fehrenbacher L, Slamon DJ, Murphy M, Novotny WF, Burchmore M, Shak S, Stewart SJ, Press M. Efficacy and safety of trastuzumab as a single agent in first-line treatment of HER2-overexpressing metastatic breast cancer. J Clin Oncol. 2002;20(3):719–26.

    Article  CAS  PubMed  Google Scholar 

  5. Pegram M, Hsu S, Lewis G, Pietras R, Beryt M, Sliwkowski M, Coombs D, Baly D, Kabbinavar F, Slamon D. Inhibitory effects of combinations of HER-2/neu antibody and chemotherapeutic agents used for treatment of human breast cancers. Oncogene. 1999;18(13):2241–51.

    Article  CAS  PubMed  Google Scholar 

  6. Slamon DJ, Leyland-Jones B, Shak S, Fuchs H, Paton V, Bajamonde A, Fleming T, Eiermann W, Wolter J, Pegram M, Baselga J, Norton L. Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2. N Engl J Med. 2001;344(11):783–92.

    Article  CAS  PubMed  Google Scholar 

  7. Marty M, Cognetti F, Maraninchi D, Snyder R, Mauriac L, Tubiana-Hulin M, Chan S, Grimes D, Antón A, Lluch A, Kennedy J, O’Byrne K, Conte P, Green M, Ward C, Mayne K, Extra JM. 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. 2005;23(19):4265–74.

    Article  CAS  PubMed  Google Scholar 

  8. Hudis CA. Trastuzumab–mechanism of action and use in clinical practice. N Engl J Med. 2007;357(1):39–51.

    Article  CAS  PubMed  Google Scholar 

  9. Andersson M, Lidbrink E, Bjerre K, Wist E, Enevoldsen K, Jensen AB, et al. Phase III randomized study comparing docetaxel plus trastuzumab with vinorelbine plus trastuzumab as first-line therapy of metastatic or locally advanced human epidermal growth factor receptor 2-positive breast cancer: the HERNATA study. J Clin Oncol. 2011;29:264–71.

    Article  CAS  PubMed  Google Scholar 

  10. Valero V, Forbes J, Pegram MD, Pienkowski T, Eiermann W, von Minckwitz G, et al. Multicenter phase III randomized trial comparing docetaxel and trastuzumab with docetaxel, carboplatin, and trastuzumab as first-line chemotherapy for patients with HER2-gene-amplified metastatic breast cancer (BCIRG 007 study): two highly active therapeutic regimens. J Clin Oncol. 2011;29:149–56.

    Article  CAS  PubMed  Google Scholar 

  11. Dawood S, Broglio K, Buzdar AU, Hortobagyi GN, Giordano SH. Prognosis of women with metastatic breast cancer by HER2 status and trastuzumab treatment: an institutional-based review. J Clin Oncol. 2010;28:92–8.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  12. Moja L, Tagliabue L, Balduzzi S, Parmelli E, Pistotti V, Guarneri V, D’Amico R. Trastuzumab containing regimens for early breast cancer. Cochrane Database Syst Rev. 2012;4:CD006243.

    PubMed  Google Scholar 

  13. Gianni L, Dafni U, Gelber RD, Azambuja E, Muehlbauer S, Goldhirsch A, et al. Treatment with trastuzumab for 1 year after adjuvant chemotherapy in patients with HER2-positive early breast cancer: a 4-year follow-up of a randomised controlled trial. Lancet Oncol. 2011;12:236–44.

    Article  CAS  PubMed  Google Scholar 

  14. Perez EA, Romond EH, Suman VJ, Jeong JH, Davidson NE, Geyer CE Jr, et al. Four-year follow-up of trastuzumab plus adjuvant chemotherapy for operable human epidermal growth factor receptor 2-positive breast cancer: joint analysis of data from NCCTG N9831 and NSABP B-31. J Clin Oncol. 2011;29:3366–73.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  15. Joensuu H, Bono P, Kataja V, Alanko T, Kokko R, Asola R, 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;27:5685–92.

    Article  CAS  PubMed  Google Scholar 

  16. Slamon D, Eiermann W, Robert N, Pienkowski T, Martin M, Press M, et al. Adjuvant trastuzumab in HER2-positive breast cancer. N Engl J Med. 2011;365(14):1273–83.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  17. Spielmann M, Roché H, Delozier T, Canon JL, Romieu G, Bourgeois H, et al. Trastuzumab for patients with axillary-node-positive breast cancer: results of the FNCLCC-PACS 04 trial. J Clin Oncol. 2009;27:6129–34.

    Article  CAS  PubMed  Google Scholar 

  18. Perez EA, Suman VJ, Davidson NE, Gralow JR, Kaufman PA, Visscher DW, et al. Sequential versus concurrent trastuzumab in adjuvant chemotherapy for breast cancer. J Clin Oncol. 2011;29:4491–7.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  19. Romond EH, Perez EA, Bryant J, Suman VJ, Geyer CE Jr, Davidson NE, et al. Trastuzumab plus adjuvant chemotherapy for operable HER-2 positive breast cancer. N Engl J Med. 2005;353:1673–84.

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  21. Goldhirsch A, Gelber RD, Piccart-Gebhart MJ, de Azambuja E, Procter M, Suter TM. 2 years versus 1 year of adjuvant trastuzumab for HER2-positive breast cancer (HERA): an open-label, randomised controlled trial. Lancet. 2013;382(9897):1021–8.

    Article  CAS  PubMed  Google Scholar 

  22. Zhou Q, Yin W, Du Y, Lu J. For or against adjuvant trastuzumab for pT1a-bN0M0 breast cancer patients with HER2-positive tumors: a meta-analysis of published literatures. PLoS One. 2014;9(1):e83646.

    Article  PubMed Central  PubMed  Google Scholar 

  23. O’Sullivan CC, Bradbury I, de Azambuja E, Perez EA, Rastogi P, Spielmann M, Joensuu H, Ballman KV, Costantino JP, Delaloge S, Zardavas D, Piccart-Gebhart M, Zujewski JA, Holmes E, Gelber RD. Efficacy of adjuvant trastuzumab compared with no trastuzumab for patients with HER2-positive breast cancer and tumors ≤ 2 cm: a meta-analysis of teh randomized trastuzumab trials. Presented at 2014 ASCO Annual Meeting.

    Google Scholar 

  24. Tolaney SM, Barry WT, Dang CT, Yardley DA, Moy B, Marcom PK, Albain KS, Rugo HS Ellis M, Shapira I, Wolff AC, Carey LA, Overmoyer BA, Partridge AH, Guo H, Hudls CA, Krop IE, Burstein HJ, Winer EP. Adjuvant paclitaxel and trastuzumab for node negative Her2+ breast cancer. Presented at San Antonio Breast Cancer Symposium 2013.

    Google Scholar 

  25. Jones SE, Collea R, Paul D, Sedlacek S, Favret AM, Gore I Jr, Lindquist DL, Holmes FA, Allison MA, Brooks BD, Portillo RM, Vukelja SJ, Steinberg MS, Stokoe C, Crockett MW, Wang Y, Asmar L, Robert NJ, O’Shaughnessy J. Adjuvant docetaxel and cyclophosphamide plus trastuzumab in patients with HER2-amplified early stage breast cancer: a single-group, open-label, phase 2 study. Lancet. 2013;14:1121–8.

    Article  CAS  PubMed  Google Scholar 

  26. Pivot X, Romieu G, Bonnefoi H, Pierga JY, Kerbrat P, Guastalla JP, et al. 6 months versus 12 months of adjuvant trastuzumab for patients with HER2-positive early breast cancer (PHARE): a randomised phase 3 trial. Lancet. 2013;14:741–8.

    Article  CAS  PubMed  Google Scholar 

  27. Buzdar AU, Ibrahim NK, Francis D, Booser DJ, Thomas ES, Theriault RL, et al. Significantly higher pathologic complete remission rate after neoadjuvant therapy with trastuzumab, paclitaxel, and epirubicin chemotherapy: results of a randomized trial in human epidermal growth factor receptor 2-positive operable breast cancer. J Clin Oncol. 2005;23:3676–85.

    Article  CAS  PubMed  Google Scholar 

  28. Gianni L, Eiermann W, Semiglazov V, Manikhas A, Lluch A, Tjulandin S, et al. Neoadjuvant chemotherapy with trastuzumab followed by adjuvant trastuzumab versus neoadjuvant chemotherapy alone, in patients with HER2-positive locally advanced breast cancer (the NOAH trial): a randomised controlled superiority trial with a parallel HER2-negative cohort. Lancet. 2010;375:377–84.

    Article  CAS  PubMed  Google Scholar 

  29. Untch M, Rezai M, Loibl S, Fasching PA, Huober J, Tesch H, et al. Neoadjuvant treatment with trastuzumab in HER2-positive breast cancer: results from the GeparQuattro study. J Clin Oncol. 2010;28:2024–31.

    Article  CAS  PubMed  Google Scholar 

  30. Crone SA, Zhao YY, Fan L, Gu Y, Minamisawa S, Liu Y, et al. ErbB2 is essential in the prevention of dilated cardiomyopathy. Nat Med. 2002;8:459–65.

    Article  CAS  PubMed  Google Scholar 

  31. Guarneri V, Barbieri E, Dieci MV, Piacentini F, Conte P. Anti-HER2 neoadjuvant and adjuvant therapies in HER2 positive breast cancer. Cancer Treat Rev. 2010;36(Suppl. 3):S62–6.

    Article  CAS  PubMed  Google Scholar 

  32. Telli ML, Hunt SA, Carlson RW, Guardino AE. Trastuzumab-related cardiotoxicity: calling into question the concept of reversibility. J Clin Oncol. 2007;25:3525–33.

    Article  CAS  PubMed  Google Scholar 

  33. Bowles EJ, Wellman R, Feigelson HS, Onitilo AA, Freedman AN, Delate T, et al. Risk of heart failure in breast cancer patients after anthracycline and trastuzumab treatment: a retrospective cohort study. J Natl Cancer Inst. 2012;104:1293–305.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  34. Chavez-MacGregor M, Zhang N, Buchholz TA, Zhang Y, Niu J, Elting L, Smith BD, Hortobagyi GN, Giordano SH. Trastuzumab-related cardiotoxicity among older patients with breast cancer. J Clin Oncol. 2013;33:4222–8.

    Article  Google Scholar 

  35. Rayson D, Suter TM, Jackisch C, van der Vegt S, Bermejo B, van den Bosch J, Vivanco GL, van Gent AM, Wildiers H, Torres A, Provencher L, Temizkan M, Chirgwin J, Canon JL, Ferrandina G, Srinivasan S, Zhang L, Richel DJ. Cardiac safety of adjuvant pegylated liposomal doxorubicin with concurrent trastuzumab: a randomized phase II trial. Ann Oncol. 2012;23:1780–8.

    Article  CAS  PubMed  Google Scholar 

  36. Xia W, Liu LH, Ho P, Spector NL. Truncated ErbB2 receptor (p95ErbB2) is regulated by heregulin through heterodimer formation with ErbB3 yet remains sensitive to the dual EGFR/ErbB2 kinase inhibitor GW572016. Oncogene. 2004;23:646–53.

    Article  CAS  PubMed  Google Scholar 

  37. Burstein HJ, Storniolo AM, Franco S, Forster J, Stein S, Rubin S, Salazar VM, Blackwell KL. A phase II study of lapatinib monotherapy in chemotherapy-refractory HER2-positive and HER2-negative advanced or metastatic breast cancer. Ann Oncol. 2008;19:1068–74.

    Article  CAS  PubMed  Google Scholar 

  38. Gomez HL, Doval DC, Chavez MA, Ang PC, Aziz Z, Nag S, Ng C, Franco SX, Chow LW, Arbushites MC, Casey MA, Berger MS, Stein SH, Sledge GW. Efficacy and safety of lapatinib as first-line therapy for ErbB2-amplified locally advanced or metastatic breast cancer. J Clin Oncol. 2008;26:2999–3005.

    Article  CAS  PubMed  Google Scholar 

  39. Geyer CE, Forster J, Lindquist D, Chan S, Romieu CG, Pienkowski T, Jagiello-Gruszfeld A, Crown J, Chan A, Kaufman B, Skarlos D, Campone M, Davidson N, Berger M, Oliva C, Rubin SD, Stein S, Cameron D. Lapatinib plus capecitabine for HER2-positive advanced breast cancer. N Engl J Med. 2006;355:2733–43.

    Article  CAS  PubMed  Google Scholar 

  40. Cameron D, Casey M, Press M, Lindquist D, Pienkowski T, Romieu CG, et al. A phase III randomized comparison of lapatinib plus capecitabine versus capecitabine alone in women with advanced breast cancer that has progressed on trastuzumab: updated efficacy and biomarker analyses. Breast Cancer Res Treat. 2008;112:533–43.

    Article  CAS  PubMed  Google Scholar 

  41. Cameron D, Casey M, Oliva C, Newstat B, Imwalle B, Geyer CE. Lapatinib plus capecitabine in women with HER-2-positive advanced breast cancer: final survival analysis of a phase III randomized trial. Oncologist. 2010;15:924–34.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  42. Pivot X, Semiglazov V, urawski BZ, Allerton R, Fabi A, Ciruelos E, et al. Cerebel (EGF111438): an open label randomized phase III study comparing the incidence of CNS metastases in patients (pts) with HER2+ metastatic breast cancer (MBC), treated with lapatinib plus capecitabine (LC) versus trastuzumab plus capecitabine (TC). Presented at the European Society for Medical Oncology Congress 2012; Abstract LBA11.

    Google Scholar 

  43. Xu B, Guan Z, Sheng Z, Tong Z, Jiang Z, Yang JI, et al. Association of PTEN loss and PI3KCA mutations on outcome in HER2+ metastatic breast cancer patients treated with first-line Lapatinib plus Paclitaxel or paclitaxel alone. Presented at San Antonio Breast Cancer Symposium 2011; Abstract S3–3.

    Google Scholar 

  44. Piccart-Gebhart MJ, et al. First results from the phase III ALTTO trial (BIG 2–06; NCCTG [Alliance] N063D) comparing one year of anti-HER2 therapy with lapatinib alone (L), trastuzumab alone (T), their sequence (T→L), or their combination (T+L) in the adjuvant treatment of HER2-positive early breast cancer (EBC). Presented at the American Society of Clinical Oncology Annual Meeting 2014, abstract LBA4.

    Google Scholar 

  45. Goss P, Smith I, O’Shaugnessy J, Ejlertsen B, Kaufmann M, Boyle F, et al. Results of a randomized, double-blind, multicenter, placebo controlled study of adjuvant lapatinib in women with early-stage Erb2-overexpressing braeast cancer. Presented at San Antonio Breast Cancer Symposium, 2011; Abstract S4–7.

    Google Scholar 

  46. Baselga J, Bradbury I, Eidtmann H, Di Cosimo S, de Azambuja E, Aura C, Gómez H, Dinh P, Fauria K, Van Dooren V, Aktan G, Goldhirsch A, Chang TW, Horváth Z, Coccia-Portugal M, Domont J, Tseng LM, Kunz G, Sohn JH, Semiglazov V, Lerzo G, Palacova M, Probachai V, Pusztai L, Untch M, Gelber RD, Piccart-Gebhart M. NeoALTTO study team. Lapatinib with trastuzumab for HER2-positive early breast cancer (NeoALTTO): a randomised, open-label, multicentre, phase 3 trial. Lancet. 2012;379:633–40.

    Article  CAS  PubMed  Google Scholar 

  47. Untch M, Loibl S, Bischoff J, Eidtmann H, Kaufmann M, Blohmer JU, et al. Lapatinib versus trastuzumab in combination with neoadjuvant anthracycline-taxane-based chemotherapy (GeparQuinto, GBG 44): a randomised phase 3 trial. Lancet Oncol. 2012;13:135–44.

    Article  CAS  PubMed  Google Scholar 

  48. Scaltriti M, Chandarlapaty S, Prudkin L, Aura C, Jimenez J, Angelini PD, et al. Clinical benefit of lapatinib-based therapy in patients with human epidermal growth factor receptor 2-positive breast tumors coexpressing the truncated p95HER2 receptor. Clin Cancer Res. 2010;16:2688–95.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  49. Nahta R, Shabaya S, Ozbay T, Rowe DL. Personalizing HER2-targeted therapy in metastatic breast cancer beyond HER2 status: what we have learned from clinical specimens. Curr Pharmacogenomics Person Med. 2009;7:263–74.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  50. Xia W, Husain I, Liu L, Bacus S, Saini S, Spohn J, et al. Lapatinib antitumor activity is not dependent upon phosphatase and tensin homologue deleted on chromosome 10 in ErbB2-overexpressing breast cancers. Cancer Res. 2007;67:1170–5.

    Article  CAS  PubMed  Google Scholar 

  51. Xia W, Bacus S, Hegde P, Husain I, Strum J, Liu L, et al. A model of acquired autoresistance to a potent ErbB2 tyrosine kinase inhibitor and a therapeutic strategy to prevent its onset in breast cancer. Proc Natl Acad Sci U S A. 2006;103:7795–800.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  52. Cortés J, Baselga J, Petrella T, Gelmon K, Fumoleau P, Verma S, et al. Pertuzumab monotherapy following trastuzumab-based treatment: activity and tolerability in patients with advanced HER2- positive breast cancer. Presented at American Society of Clinical oncology Annual Meeting 2009; Abstract 1022.

    Google Scholar 

  53. Gianni L, Lladó A, Bianchi G, Cortes J, Kellokumpu-Lehtinen PL, Cameron DA, et al. Open-label, phase II, multicenter, randomized study of the efficacy and safety of two dose levels of Pertuzumab, a human epidermal growth factor receptor 2 dimerization inhibitor, in patients with human epidermal growth factor receptor 2-negative metastatic breast cancer. J Clin Oncol. 2010;28:1131–7.

    Article  CAS  PubMed  Google Scholar 

  54. Baselga J, Gelmon KA, Verma S, Wardley A, Conte P, Miles D, et al. Phase II trial of pertuzumab and trastuzumab in patients with human epidermal growth factor receptor 2-positive metastatic breast cancer that progressed during prior trastuzumab therapy. J Clin Oncol. 2010;28:1138–44.

    Article  CAS  PubMed  Google Scholar 

  55. Baselga J, Cortés J, Kim SB, Im SA, Hegg R, Im YH, et al. Pertuzumab plus trastuzumab plus docetaxel for metastatic breast cancer. N Engl J Med. 2012;366:109–19.

    Article  CAS  PubMed  Google Scholar 

  56. http://www.accessdata.fda.gov/drugsatfda_docs/label/2013/125409s051lbl.pdf.

  57. Burris HA 3rd, Rugo HS, Vukelja SJ, Vogel CL, Borson RA, Limentani S, Tan-Chiu E, Krop IE, Michaelson RA, Girish S, Amler L, Zheng M, Chu YW, Klencke B, O’Shaughnessy JA. Phase II study of the antibody drug conjugate trastuzumab-DM1 for the treatment of human epidermal growth factor receptor 2 (HER2)-positive breast cancer after prior HER2-directed therapy. J Clin Oncol. 2011;29:398–405.

    Article  CAS  PubMed  Google Scholar 

  58. Krop IE, Lorusso P, Miller KD, Modi S, Yardley D, Rodriguez G, Guardino E, Lu M, Zheng M, Girish S, Amler L, Winer EP, Rugo HS. A phase II study of trastuzumab emtansine in patients with human epidermal growth factor receptor 2-positive metastatic breast cancer who were previously treated with trastuzumab, lapatinib, an anthracycline, a taxane, and capecitabine. J Clin Oncol. 2012;30:3234–41.

    Article  CAS  PubMed  Google Scholar 

  59. Hurvitz SA, Dirix L, Kocsis J, et al. Trastuzumab emtansine (T-DM1) versus trastuzumab + docetaxel in previously untreated HER2-positive metastatic breast cancer (MBC): primary results of a randomized, multiventer, open-label phase II study 5TDM4450g/BO21976). Presented at: European Multidisciplinary Cancer Congress (ECCO/ESMO); Abstract 5001.

    Google Scholar 

  60. http://www.accessdata.fda.gov/drugsatfda_docs/label/2013/125427lbl.pdf.

  61. Verma S, Miles D, Gianni L, Krop IE, Welslau M, Baselga J, et al. Trastuzumab emtansine for HER2-positive advanced breast cancer. N Engl J Med. 2012;367:1783–91.

    Article  CAS  PubMed  Google Scholar 

  62. Krop IE, Kim S-B, González-Martín A, LoRusso PM, Ferrero J-M, Smitt M, Yu R, Leung AC, Wildiers H, et al. Trastuzumab emtansine versus treatment of physician’s choice for pretreated HER2-positive advanced breast cancer (TH3RESA): a randomised, open-label, phase 3 trial. Lancet. 2014;15:689–99.

    Article  CAS  PubMed  Google Scholar 

  63. Burstein HJ, Sun Y, Dirix LY, Jiang Z, Paridaens R, Tan AR, et al. Neratinib, an irreversible ErbB receptor tyrosine kinase inhibitor, in patients with advanced ErbB2-positive breast cancer. J Clin Oncol. 2010;28:1301–7.

    Article  CAS  PubMed  Google Scholar 

  64. Martin M, Bonneterre J, Geyer CE Jr, Ito Y, Ro J, Lang I, Kim SB, Germa C, Vermette J, Wang K, Awada A. A phase two randomised trial of neratinib monotherapy versus lapatinib plus capecitabine combination therapy in patients with HER2+ advanced breast cancer. Eur J Cancer. 2013;49(18):3763–72.

    Article  CAS  PubMed  Google Scholar 

  65. Blackwell KL, Burstein HJ, Storniolo AM, Rugo HS, Sledge G, Aktan G, et al. Overall survival benefit with lapatinib in combination with trastuzumab for patients with human epidermal growth factor receptor 2-positive metastatic breast cancer: final results from the EGF104900 Study. J Clin Oncol. 2012;30:2585–92.

    Article  CAS  PubMed  Google Scholar 

  66. Chang J, Mayer IA, Forero-Torres A, Nanda R, Goetz MP, Rodriguez AA, et al. TBCRC 006: a multicenter phase II study of neoadjuvant lapatinib and trastuzumab in patients with HER2-overexpressing breast cancer. Presented at American Society of Clinical oncology Annual Meeting 2011; Abstract 505.

    Google Scholar 

  67. Guarneri V, Frassoldati A, Bottini A, Cagossi K, Bisagni G, Sarti S, et al. Preoperative chemotherapy plus trastuzumab, lapatinib, or both in human epidermal growth factor receptor 2-positive operable breast cancer: results of the randomized phase II CHER-LOB study. J Clin Oncol. 2012;30:1989–95.

    Article  CAS  PubMed  Google Scholar 

  68. Gianni L, Pienkowski T, Im YH, Roman L, Tseng LM, Liu MC, et al. Efficacy and safety of neoadjuvant pertuzumab and trastuzumab in women with locally advanced, inflammatory, or early HER2-positive breast cancer (NeoSphere): a randomised multicentre, open-label, phase 2 trial. Lancet Oncol. 2012;13:25–32.

    Article  CAS  PubMed  Google Scholar 

  69. Kaufman B, Mackey JR, Clemens MR, et al. Trastuzumab plus anastrozole versus anastrozole alone for the treatment of postmenopausal women with human epidermal growth factor receptor 2-positive, hormone receptor-positive metastatic breast cancer: results from the randomized TAnDEM study. J Clin Oncol. 2009;27:5529–37.

    Article  CAS  PubMed  Google Scholar 

  70. Johnston S, Pippen J Jr, Pivot X, et al. Lapatinib combined with letrozole versus letrozole and placebo as first-line therapy for postmenopausal hormone-receptor-positive metastatic breast cancer. J Clin Oncol. 2009;27:5538–46.

    Article  CAS  PubMed  Google Scholar 

  71. Andre F, Campone M, O’Regan R, Manlius C, Massacesi C, Sahmoud T, et al. Phase I study of everolimus plus weekly paclitaxel and trastuzumab in patients with metastatic breast cancer pretreated with trastuzumab. J Clin Oncol. 2010;28:5110–5.

    Article  CAS  PubMed  Google Scholar 

  72. Morrow PK, Wulf GM, Ensor J, Booser DJ, Moore JA, Flores PR, et al. Phase I/II study of trastuzumab in combination with everolimus (RAD001) in patients with HER2-overexpressing metastatic breast cancer who progressed on trastuzumab-based therapy. J Clin Oncol. 2011;29:3126–32.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  73. André F, O’Regan R, Ozguroglu M, Toi M, Xu B, Jerusalem G, Masuda N, Wilks S, Arena F, Isaacs C, Yap YS, Papai Z, Lang I, Armstrong A, Lerzo G, White M, Shen K, Litton J, Chen D, Zhang Y, Ali S, Taran T, Gianni L. Everolimus for women with trastuzumab-resistant, HER2-positive, advanced breast cancer (BOLERO-3): a randomised, double-blind, placebo-controlled phase 3 trial. Lancet. 2014;15(6):580–91.

    Article  PubMed  Google Scholar 

  74. Pegram M, Chan D, Dichmann RA. 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 [abstract 301]. Breast Cancer Res Treat. 2006;100(Suppl. 1):S28.

    Google Scholar 

  75. Pierga JY, Petit T, Delozier T, Ferrero JM, Campone M, Gligorov J, et al. Neoadjuvant bevacizumab, trastuzumab, and chemotherapy for primary inflammatory HER2-positive breast cancer (BEVERLY-2): an open-label, single-arm phase 2 study. Lancet Oncol. 2012;13:375–84.

    Article  CAS  PubMed  Google Scholar 

  76. Gianni L, Romieu GH, Lichinitser M, Serrano SV, Mansutti M, Pivot X, Mariani P, Andre F, Chan A, Lipatov O, Chan S, Wardley A, Greil R, Moore N, Prot S, Pallaud C, Semiglazov V. AVEREL: a randomized phase III trial evaluating bevacizumab in combination with docetaxel and trastuzumab as first-line therapy for HER2-positive locally recurrent/metastatic breast cancer. J Clin Oncol. 2013;31:1719–25.

    Article  CAS  PubMed  Google Scholar 

  77. Slamon D, Swain S, Buyse M, Martin M, Geyer C, Im Y-H, Pienkowski T, Kim S-B, Robert N, Steger G, Crown J, Verma S, Eiermann W, Costantino J, Im SA, Mamounas E, Schwartzberg L, Paterson A, Mackey J, Provencher L, Press M, Thirlwell M, Bee-Monteanu V, Henschel V, Crepelle-Flechais A, Wolmark N. BETH: a randomized phase III Study evaluating adjuvant Bevacizumab added to Trastuzumab/chemotherapy for treatment of HER2+ early breast cancer. Presented at San Antonio Breast Cancer Symposium 2013.

    Google Scholar 

  78. Pegram M, Liao J. Trastuzumab treatment in multiple lines: current data and future directions. Clin Breast Cancer. 2012;12:10–8.

    Article  CAS  PubMed  Google Scholar 

  79. von Minckwitz G du Bois A Schmidt M Maass N Cufer T de Jongh FE, et al. Trastuzumab beyond progression in human epidermal growth factor receptor 2-positive advanced breast cancer: a German breast group 26/breast international group 03–05 study. J Clin Oncol. 2009;27:1999–2006.

    Article  Google Scholar 

  80. Cortés J, Fumoleau P, Bianchi GV, Petrella TM, Gelmon K, Pivot X, et al. Pertuzumab monotherapy after trastuzumab-based treatment and subsequent reintroduction of trastuzumab: activity and tolerability in patients with advanced human epidermal growth factor receptor 2-positive breast cancer. J Clin Oncol. 2012;30:1594–600.

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Surgery, Oncology and Gastroenterology, Istituto Oncologico Veneto IRCCS, University of Padova and Medical Oncology 2, via Gattamelata 64, 35128, Padova, Italy

    Maria Vittoria Dieci, Valentina Guarneri, Carlo Alberto Giorgi & Prof. Pierfranco Conte

Authors
  1. Maria Vittoria Dieci
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Valentina Guarneri
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Carlo Alberto Giorgi
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Prof. Pierfranco Conte
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Pierfranco Conte .

Editor information

Editors and Affiliations

  1. Department of Surgical, Oncological and Oral Sciences, University of Palermo, Palermo, Italy

    Antonio Russo

  2. Catalan Institute of Oncology, University Hospital Germans Trias i Pujol, Badalona, Barcelona, Spain

    Rafael Rosell

  3. Oncology Department, Antwerp University Hospital, Edegem, Antwerpen, Belgium

    Christian Rolfo

Rights and permissions

Reprints and permissions

Copyright information

© 2015 Springer Science+Business Media New York

About this chapter

Cite this chapter

Dieci, M., Guarneri, V., Giorgi, C., Conte, P. (2015). Targeted Therapies for HER2-positive Breast Cancer. In: Russo, A., Rosell, R., Rolfo, C. (eds) Targeted Therapies for Solid Tumors. Current Clinical Pathology. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-2047-1_6

Download citation

  • DOI: https://doi.org/10.1007/978-1-4939-2047-1_6

  • Published:

  • Publisher Name: Humana Press, New York, NY

  • Print ISBN: 978-1-4939-2046-4

  • Online ISBN: 978-1-4939-2047-1

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation