Skip to main content
SpringerLink
Log in

Tyrosine Kinase Inhibitors

  • Chapter
  • First Online:
Breast Disease

  • 1629 Accesses

Abstract

Breast cancer is the most common cancer in women worldwide. Although various subgroups are defined according to the expression of hormones and ErbB family receptors, it is well known that this disease is more heterogeneous than its classification system suggests. As new effective therapeutic choices are developed and used clinically, resistance to these new agents is also being observed. The most promising new anti-HER therapies are T-DM1 and pertuzumab, which has been evaluated in trastuzumab-resistant patients and also in a first-line setting with trastuzumab. The dual blockage of HER seems to be a favorable approach for these patients; however, the downstream signaling steps can be activated to overcome the tyrosine kinase inhibition. Because tumor cells can adapt themselves by using alternative pathways to maintain proliferation, providing a sufficient treatment approach also requires the consideration of possible escape mechanisms in tumor cells. By inhibiting tyrosine kinases combined with another agent that affects downstream factors of the PI3K/AKT/mTOR pathway, drug resistance in breast cancer can be overcome or delayed. In this chapter, we discuss the new tyrosine kinase inhibitors that inhibit more than only HER-2 and discuss some ongoing clinical trials in this area. In so doing, we hope to provide information for overcoming tyrosine kinase drug resistance and to identify the ideal settings for these treatment choices according to recent data.

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 219.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Saxena R, Dwivedi A. ErbB family receptor inhibitors as therapeutic agents in breast cancer: current status and future clinical perspective. Med Res Rev. 2012;32(1):166–215. Review.

    Article  CAS  PubMed  Google Scholar 

  2. Broekman F, Giovannetti E, Peters GJ. Tyrosine kinase inhibitors: multi-targeted or single-targeted? World J Clin Oncol. 2011;2(2):80–93.

    Article  PubMed  PubMed Central  Google Scholar 

  3. Konecny GE, Pegram MD, Venkatesan N, Finn R, Yang G, Rahmeh M, et al. Activity of the dual kinase inhibitor lapatinib (GW572016) against HER-2-overexpressing and trastuzumab-treated breast cancer cells. Cancer Res. 2006;66(3):1630–9.

    Article  CAS  PubMed  Google Scholar 

  4. Scaltriti M, Rojo F, Ocana A, Anido J, Guzman M, Cortes J, et al. Expression of p95HER2, a truncated form of the HER2 receptor, and response to anti-HER2 therapies in breast cancer. J Natl Cancer Inst. 2007;99(8):628–38. Research Support, Non-U.S. Gov’t.

    Article  CAS  PubMed  Google Scholar 

  5. Di Leo A, Gomez HL, Aziz Z, Zvirbule Z, Bines J, Arbushites MC, et al. Phase III, double-blind, randomized study comparing lapatinib plus paclitaxel with placebo plus paclitaxel as first-line treatment for metastatic breast cancer. J Clin Oncol Off J Am Soc Clin Oncol. 2008;26(34):5544–52. Clinical Trial, Phase III Multicenter Study Randomized Controlled Trial Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov’t.

    Article  Google Scholar 

  6. 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(3):533–43. Clinical Trial, Phase III Randomized Controlled Trial Research Support, Non-U.S. Gov’t.

    Article  CAS  PubMed  Google Scholar 

  7. Blackwell KL, Burstein HJ, Storniolo AM, Rugo H, Sledge G, Koehler M, et al. Randomized study of Lapatinib alone or in combination with trastuzumab in women with ErbB2-positive, trastuzumab-refractory metastatic breast cancer. J Clin Oncol Off J Am Soc Clin Oncol. 2010;28(7):1124–30. Clinical Trial, Phase III Multicenter Study Randomized Controlled Trial Research Support, Non-U.S. Gov’t.

    Article  CAS  Google Scholar 

  8. 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 Off J Am Soc Clin Oncol. 2012;30(21):2585–92. Clinical Trial, Phase III Multicenter Study Randomized Controlled Trial Research Support, Non-U.S. Gov’t.

    Article  CAS  Google Scholar 

  9. Baselga J, Bradbury I, Eidtmann H, Di Cosimo S, de Azambuja E, Aura C, et al. Lapatinib with trastuzumab for HER2-positive early breast cancer (NeoALTTO): a randomised, open-label, multicentre, phase 3 trial. Lancet. 2012;379(9816):633–40. Clinical Trial, Phase III Multicenter Study Randomized Controlled Trial Research Support, Non-U.S. Gov’t.

    Article  CAS  PubMed  Google Scholar 

  10. 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(2):135–44. Clinical Trial, Phase III Comparative Study Randomized Controlled Trial Research Support, Non-U.S. Gov’t.

    Article  CAS  PubMed  Google Scholar 

  11. Guarneri V, Frassoldati A, Piacentini F, Jovic G, Giovannelli S, Oliva C, et al. Preoperative chemotherapy plus lapatinib or trastuzumab or both in HER2-positive operable breast cancer (CHERLOB Trial). Clin Breast Cancer. April 2008. Vol 8 No. 2 192–194. Clinical Trial, Phase II Randomized Controlled Trial Research Support, Non-U.S. Gov’t.

    Google Scholar 

  12. Xia W, Bacus S, Husain I, Liu L, Zhao S, Liu Z, et al. Resistance to ErbB2 tyrosine kinase inhibitors in breast cancer is mediated by calcium-dependent activation of RelA. Mol Cancer Ther. 2010;9(2):292–9. Research Support, Non-U.S. Gov’t.

    Article  CAS  PubMed  Google Scholar 

  13. Johnston S, Pippen Jr J, Pivot X, Lichinitser M, Sadeghi S, Dieras V, 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 Off J Am Soc Clin Oncol. 2009;27(33):5538–46. Clinical Trial, Phase III Comparative Study Multicenter Study Randomized Controlled Trial Research Support, Non-U.S. Gov’t.

    Article  CAS  Google Scholar 

  14. Kaufman B, Mackey JR, Clemens MR, Bapsy PP, Vaid A, Wardley A, 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 phase III TAnDEM study. J Clin Oncol Off J Am Soc Clin Oncol. 2009;27(33):5529–37. Clinical Trial, Phase III Comparative Study Multicenter Study Randomized Controlled Trial Research Support, Non-U.S. Gov’t.

    Article  CAS  Google Scholar 

  15. Brockhoff G, Heckel B, Schmidt-Bruecken E, Plander M, Hofstaedter F, Vollmann A, et al. Differential impact of cetuximab, pertuzumab and trastuzumab on BT474 and SK-BR-3 breast cancer cell proliferation. Cell Prolif. 2007;40(4):488–507. Research Support, Non-U.S. Gov’t.

    Article  CAS  PubMed  Google Scholar 

  16. 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 Off J Am Soc Clin Oncol. 2010;28(7):1138–44. Clinical Trial, Phase II Multicenter Study Research Support, Non-U.S. Gov’t.

    Article  CAS  Google Scholar 

  17. Baselga J, Cortes 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(2):109–19. Comparative Study Multicenter Study Randomized Controlled Trial Research Support, Non-U.S. Gov’t.

    Article  CAS  PubMed  Google Scholar 

  18. 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(1):25–32. Clinical Trial, Phase II Multicenter Study Randomized Controlled Trial Research Support, Non-U.S. Gov’t.

    Article  CAS  PubMed  Google Scholar 

  19. Schneeweiss A, Chia S, Hickish T, Harvey V, Hegg R, Tausch C, et al. Pertuzumab and trastuzumab in combination with an anthracycline-containing or an anthracycline-free standard chemotherapy in the neoadjuvant treatment of HER2-positive breast cancer (TRYPHAENA). Eur J Cancer. 2012;48:S96–S.

    Article  Google Scholar 

  20. Isakoff SJ, Baselga J. Trastuzumab-DM1: building a chemotherapy-free road in the treatment of human epidermal growth factor receptor 2-positive breast cancer. J Clin Oncol Off J Am Soc Clin Oncol. 2011;29(4):351–4. Comment Editorial.

    Article  CAS  Google Scholar 

  21. Welslau M, Dieras V, Sohn JH, Hurvitz SA, Lalla D, Fang L, et al. Patient-reported outcomes from EMILIA, a randomized phase 3 study of trastuzumab emtansine (T-DM1) versus capecitabine and lapatinib in human epidermal growth factor receptor 2-positive locally advanced or metastatic breast cancer. Cancer. 2014;120(5):642–51. Clinical Trial, Phase III Randomized Controlled Trial Research Support, Non-U.S. Gov’t.

    Article  CAS  PubMed  Google Scholar 

  22. Krop IE, Kim SB, Gonzalez-Martin A, LoRusso PM, Ferrero JM, Smitt M, 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 Oncol. 2014;15(7):689–99. Clinical Trial, Phase III Comparative Study Multicenter Study Randomized Controlled Trial Research Support, Non-U.S. Gov’t.

    Article  CAS  PubMed  Google Scholar 

  23. Hurvitz SA, Dirix L, Kocsis J, Bianchi GV, Lu J, Vinholes J, et al. Phase II randomized study of trastuzumab emtansine versus trastuzumab plus docetaxel in patients with human epidermal growth factor receptor 2-positive metastatic breast cancer. J Clin Oncol Off J Am Soc Clin Oncol. 2013;31(9):1157–63.

    Article  CAS  Google Scholar 

  24. Lopez-Tarruella S, Jerez Y, Marquez-Rodas I, Martin M. Neratinib (HKI-272) in the treatment of breast cancer. Future Oncol. 2012;8(6):671–81. Review.

    Article  CAS  PubMed  Google Scholar 

  25. 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 Off J Am Soc Clin Oncol. 2010;28(8):1301–7. Clinical Trial, Phase II Comparative Study Multicenter Study Research Support, Non-U.S. Gov’t.

    Article  CAS  Google Scholar 

  26. Saura C, Martin M, Moroose R, Harb W, Liem K, Arena F, et al. Safety of neratinib (HKI-272) in combination with capecitabine in patients with solid tumors: a phase 1/2 study. Cancer Res. 2009;69(24):801S–2.

    Google Scholar 

  27. Park J, Liu M, Yee D, et al. Neratinib plus standard neoadjuvant chemotherapy for high-risk breast cancer: efficacy results from the I-SPY trial. 2014 AACR Annual Meeting 2014.

    Google Scholar 

  28. Lin NU, Winer EP, Wheatley D, Carey LA, Houston S, Mendelson D, et al. A phase II study of afatinib (BIBW 2992), an irreversible ErbB family blocker, in patients with HER2-positive metastatic breast cancer progressing after trastuzumab. Breast Cancer Res Treat. 2012;133(3):1057–65. Clinical Trial, Phase II Multicenter Study Research Support, Non-U.S. Gov’t.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Schuler M, Awada A, Harter P, Canon JL, Possinger K, Schmidt M, et al. A phase II trial to assess efficacy and safety of afatinib in extensively pretreated patients with HER2-negative metastatic breast cancer. Breast Cancer Res Treat. 2012;134(3):1149–59. Clinical Trial, Phase II Multicenter Study Research Support, Non-U.S. Gov’t.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Hurvitz SA, Shatsky R, Harbeck N. Afatinib in the treatment of breast cancer. Expert Opin Investig Drugs. 2014;23(7):1039–47.

    Article  CAS  PubMed  Google Scholar 

  31. Tang CK, Gong XQ, Moscatello DK, Wong AJ, Lippman ME. Epidermal growth factor receptor vIII enhances tumorigenicity in human breast cancer. Cancer Res. 2000;60(11):3081–7. Research Support, Non-U.S. Gov’t Research Support, U.S. Gov’t, P.H.S.

    CAS  PubMed  Google Scholar 

  32. Nicholson RI, McClelland RA, Gee JM, Manning DL, Cannon P, Robertson JF, et al. Epidermal growth factor receptor expression in breast cancer: association with response to endocrine therapy. Breast Cancer Res Treat. 1994;29(1):117–25. Clinical Trial Comparative Study Research Support, Non-U.S. Gov’t.

    Article  CAS  PubMed  Google Scholar 

  33. Nielsen TO, Hsu FD, Jensen K, Cheang M, Karaca G, Hu Z, et al. Immunohistochemical and clinical characterization of the basal-like subtype of invasive breast carcinoma. Clin Cancer Res Off J Am Assoc Cancer Res. 2004;10(16):5367–74. Research Support, U.S. Gov’t, P.H.S.

    Article  CAS  Google Scholar 

  34. von Minckwitz G, Jonat W, Fasching P, du Bois A, Kleeberg U, Luck HJ, et al. A multicentre phase II study on gefitinib in taxane- and anthracycline-pretreated metastatic breast cancer. Breast Cancer Res Treat. 2005;89(2):165–72. Clinical Trial Clinical Trial, Phase II Multicenter Study Research Support, Non-U.S. Gov’t.

    Article  CAS  Google Scholar 

  35. Polychronis A, Sinnett HD, Hadjiminas D, Singhal H, Mansi JL, Shivapatham D, et al. Preoperative gefitinib versus gefitinib and anastrozole in postmenopausal patients with oestrogen-receptor positive and epidermal-growth-factor-receptor-positive primary breast cancer: a double-blind placebo-controlled phase II randomised trial. Lancet Oncol. 2005;6(6):383–91. Clinical Trial Clinical Trial, Phase II Multicenter Study Randomized Controlled Trial Research Support, Non-U.S. Gov’t.

    Article  CAS  PubMed  Google Scholar 

  36. Fountzilas G, Pectasides D, Kalogera-Fountzila A, Skarlos D, Kalofonos HP, Papadimitriou C, et al. Paclitaxel and carboplatin as first-line chemotherapy combined with gefitinib (IRESSA) in patients with advanced breast cancer: a phase I/II study conducted by the Hellenic Cooperative Oncology Group. Breast Cancer Res Treat. 2005;92(1):1–9. Clinical Trial Clinical Trial, Phase I Clinical Trial, Phase II Multicenter Study Research Support, Non-U.S. Gov’t.

    Article  CAS  PubMed  Google Scholar 

  37. Ciardiello F, Troiani T, Caputo F, De Laurentiis M, Tortora G, Palmieri G, et al. Phase II study of gefitinib in combination with docetaxel as first-line therapy in metastatic breast cancer. Br J Cancer. 2006;94(11):1604–9. Clinical Trial, Phase II Multicenter Study.

    CAS  PubMed  PubMed Central  Google Scholar 

  38. Dennison SK, Jacobs SA, Wilson JW, Seeger J, Cescon TP, Raymond JM, et al. A phase II clinical trial of ZD1839 (Iressa) in combination with docetaxel as first-line treatment in patients with advanced breast cancer. Investig New Drugs. 2007;25(6):545–51. Clinical Trial, Phase II Multicenter Study Research Support, N.I.H., Intramural Research Support, Non-U.S. Gov’t.

    Article  CAS  Google Scholar 

  39. Arteaga CL, O’Neill A, Moulder SL, Pins M, Sparano JA, Sledge GW, et al. A phase I-II study of combined blockade of the ErbB receptor network with trastuzumab and gefitinib in patients with HER2 (ErbB2)-overexpressing metastatic breast cancer. Clin Cancer Res Off J Am Assoc Cancer Res. 2008;14(19):6277–83. Clinical Trial, Phase I Clinical Trial, Phase II Research Support, N.I.H., Extramural.

    Article  CAS  Google Scholar 

  40. Gioulbasanis I, Saridaki Z, Kalykaki A, Vamvakas L, Kalbakis K, Ignatiadis M, et al. Gefitinib in combination with gemcitabine and vinorelbine in patients with metastatic breast cancer pre-treated with taxane and anthracycline chemotherapy: a phase I/II trial. Anticancer Res. 2008;28(5B):3019–25. Clinical Trial, Phase I Clinical Trial, Phase II Research Support, Non-U.S. Gov’t.

    CAS  PubMed  Google Scholar 

  41. Smith IE, Walsh G, Skene A, Llombart A, Mayordomo JI, Detre S, et al. A phase II placebo-controlled trial of neoadjuvant anastrozole alone or with gefitinib in early breast cancer. J Clin Oncol Off J Am Soc Clin Oncol. 2007;25(25):3816–22. Clinical Trial, Phase II Randomized Controlled Trial Research Support, Non-U.S. Gov’t.

    Article  CAS  Google Scholar 

  42. Cristofanilli M, Valero V, Mangalik A, Royce M, Rabinowitz I, Arena FP, et al. Phase II, randomized trial to compare anastrozole combined with gefitinib or placebo in postmenopausal women with hormone receptor-positive metastatic breast cancer. Clin Cancer Res Off J Am Assoc Cancer Res. 2010;16(6):1904–14. Clinical Trial, Phase II Comparative Study Multicenter Study Randomized Controlled Trial Research Support, N.I.H., Extramural.

    Article  CAS  Google Scholar 

  43. Osborne CK, Neven P, Dirix LY, Mackey JR, Robert J, Underhill C, et al. Gefitinib or placebo in combination with tamoxifen in patients with hormone receptor-positive metastatic breast cancer: a randomized phase II study. Clin Cancer Res Off J Am Assoc Cancer Res. 2011;17(5):1147–59. Clinical Trial, Phase II Randomized Controlled Trial Research Support, Non-U.S. Gov’t.

    Article  CAS  Google Scholar 

  44. O’Shaughnessy J, Weckstein DJ, Vukelja SJ, McIntyre K, Krekow L, Holmes FA, et al. Preliminary results of a randomized phase II study of weekly irinotecan/carboplatin with or without cetuximab in patients with metastatic breast cancer. Breast Cancer Res Treat. 2007;106:S32–3.

    Google Scholar 

  45. Baselga J, Gomez P, Awada A, Greil R, Braga S, Climent MA, et al. The addition of cetuximab to cisplatin ıncreases overall response rate (orr) and progressıon-free survıval (pfs) ın metastatıc trıple-negatıve breast cancer (tnbc): results of a randomızed phase II study (Bali-1). Ann Oncol. 2010;21:96.

    Article  Google Scholar 

  46. Dickler MN, Cobleigh MA, Miller KD, Klein PM, Winer EP. Efficacy and safety of erlotinib in patients with locally advanced or metastatic breast cancer. Breast Cancer Res Treat. 2009;115(1):115–21. Clinical Trial, Phase II Multicenter Study.

    Article  CAS  PubMed  Google Scholar 

  47. Dickler MN, Rugo HS, Eberle CA, Brogi E, Caravelli JF, Panageas KS, et al. A phase II trial of erlotinib in combination with bevacizumab in patients with metastatic breast cancer. Clin Cancer Res Off J Am Assoc Cancer Res. 2008;14(23):7878–83. Clinical Trial, Phase II Multicenter Study Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov’t.

    Article  CAS  Google Scholar 

  48. Britten CD, Finn RS, Bosserman LD, Wong SG, Press MF, Malik M, et al. A phase I/II trial of trastuzumab plus erlotinib in metastatic HER2-positive breast cancer: a dual ErbB targeted approach. Clin Breast Cancer. 2009;9(1):16–22. Clinical Trial, Phase I Clinical Trial, Phase II Research Support, N.I.H., Extramural.

    Article  CAS  PubMed  Google Scholar 

  49. Baselga J. Targeting the phosphoinositide-3 (PI3) kinase pathway in breast cancer. Oncologist. 2011;16 Suppl 1:12–9. Research Support, Non-U.S. Gov’t Review.

    Article  PubMed  Google Scholar 

  50. Ellis MJ, Ding L, Shen D, Luo J, Suman VJ, Wallis JW, et al. Whole-genome analysis informs breast cancer response to aromatase inhibition. Nature. 2012;486(7403):353–60. Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov’t.

    CAS  PubMed  PubMed Central  Google Scholar 

  51. Kalinsky K, Jacks LM, Heguy A, Patil S, Drobnjak M, Bhanot UK, et al. PIK3CA mutation associates with improved outcome in breast cancer. Clin Cancer Res Off J Am Assoc Cancer Res. 2009;15(16):5049–59. Research Support, Non-U.S. Gov’t.

    Article  CAS  Google Scholar 

  52. Eichhorn PJ, Gili M, Scaltriti M, Serra V, Guzman M, Nijkamp W, et al. Phosphatidylinositol 3-kinase hyperactivation results in lapatinib resistance that is reversed by the mTOR/phosphatidylinositol 3-kinase inhibitor NVP-BEZ235. Cancer Res. 2008;68(22):9221–30. Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov’t.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Wang L, Zhang Q, Zhang J, Sun S, Guo H, Jia Z, et al. PI3K pathway activation results in low efficacy of both trastuzumab and lapatinib. BMC Cancer. 2011;11:248. Clinical Trial Research Support, Non-U.S. Gov’t.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Esteva FJ, Guo H, Zhang S, Santa-Maria C, Stone S, Lanchbury JS, et al. PTEN, PIK3CA, p-AKT, and p-p70S6K status: association with trastuzumab response and survival in patients with HER2-positive metastatic breast cancer. Am J Pathol. 2010;177(4):1647–56. Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov’t Research Support, U.S. Gov’t, Non-P.H.S.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Miller TW, Rexer BN, Garrett JT, Arteaga CL. Mutations in the phosphatidylinositol 3-kinase pathway: role in tumor progression and therapeutic implications in breast cancer. Breast Cancer Res BCR. 2011;13(6):224. Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov’t Review.

    Article  CAS  PubMed  Google Scholar 

  56. Ando Y, Inada-Inoue M, Mitsuma A, Yoshino T, Ohtsu A, Suenaga N, et al. Phase I dose-escalation study of buparlisib (BKM120), an oral pan-class I PI3K inhibitor, in Japanese patients with advanced solid tumors. Cancer Sci. 2014;105(3):347–53. Clinical Trial, Phase I Research Support, Non-U.S. Gov’t.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Shapiro GI, Rodon J, Bedell C, Kwak EL, Baselga J, Brana I, et al. Phase I safety, pharmacokinetic, and pharmacodynamic study of SAR245408 (XL147), an oral pan-class I PI3K inhibitor, in patients with advanced solid tumors. Clin Cancer Res Off J Am Assoc Cancer Res. 2014;20(1):233–45. Clinical Trial, Phase I Research Support, Non-U.S. Gov’t.

    Article  CAS  Google Scholar 

  58. Harari D, Yarden Y. Molecular mechanisms underlying ErbB2/HER2 action in breast cancer. Oncogene. 2000;19(53):6102–14. Research Support, Non-U.S. Gov’t Research Support, U.S. Gov’t, Non-P.H.S.Research Support, U.S. Gov’t, P.H.S. Review.

    Article  CAS  PubMed  Google Scholar 

  59. Berns K, Horlings HM, Hennessy BT, Madiredjo M, Hijmans EM, Beelen K, et al. A functional genetic approach identifies the PI3K pathway as a major determinant of trastuzumab resistance in breast cancer. Cancer Cell. 2007;12(4):395–402. Clinical Trial Multicenter Study Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov’t.

    Article  CAS  PubMed  Google Scholar 

  60. Baselga J, Fumoleau P, Gil M, Colomer R, Roche H, Cortes-Funes H, et al. Phase II, 3-arm study of CCI-779 in combination with letrozole in postmenopausal women with locally advanced or metastatic breast cancer: preliminary results. J Clin Oncol. 2004;22(14):13S–S.

    Google Scholar 

  61. Chow LWC, Sun Y, Jassem J, Baselga J, Hayes DF, Wolff AC, et al. Phase 3 study of temsirolimus with letrozole or letrozole alone in postmenopausal women with locally advanced or metastatic breast cancer. Breast Cancer Res Treat. 2006;100:S286–S.

    Google Scholar 

  62. Ellard SL, Clemons M, Gelmon KA, Norris B, Kennecke H, Chia S, et al. Randomized phase II study comparing two schedules of everolimus in patients with recurrent/metastatic breast cancer: NCIC Clinical Trials Group IND.163. J Clin Oncol Off J Am Soc Clin Oncol. 2009;27(27):4536–41. Clinical Trial, Phase II Comparative Study Multicenter Study Randomized Controlled Trial Research Support, Non-U.S. Gov’t.

    Article  CAS  Google Scholar 

  63. 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 Off J Am Soc Clin Oncol. 2010;28(34):5110–5. Clinical Trial, Phase I Multicenter Study Research Support, Non-U.S. Gov’t.

    Article  CAS  Google Scholar 

  64. Jerusalem G, Fasolo A, Dieras V, Cardoso F, Bergh J, Vittori L, et al. Phase I trial of oral mTOR inhibitor everolimus in combination with trastuzumab and vinorelbine in pre-treated patients with HER2-overexpressing metastatic breast cancer. Breast Cancer Res Treat. 2011;125(2):447–55. Clinical Trial, Phase I Multicenter Study Research Support, Non-U.S. Gov’t.

    Article  CAS  PubMed  Google Scholar 

  65. 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 Off J Am Soc Clin Oncol. 2011;29(23):3126–32. Clinical Trial, Phase IClinical Trial, Phase II Multicenter Study Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov’t.

    Article  CAS  Google Scholar 

  66. Beaver JA, Park BH. The BOLERO-2 trial: the addition of everolimus to exemestane in the treatment of postmenopausal hormone receptor-positive advanced breast cancer. Future Oncol. 2012;8(6):651–7. Clinical Trial, Phase III Randomized Controlled Trial.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Yardley DA, Noguchi S, Pritchard KI, Burris 3rd HA, Baselga J, Gnant M, et al. Everolimus plus exemestane in postmenopausal patients with HR(+) breast cancer: BOLERO-2 final progression-free survival analysis. Adv Ther. 2013;30(10):870–84. Clinical Trial, Phase III Multicenter Study Randomized Controlled Trial Research Support, Non-U.S. Gov’t.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Lueftner D, Schuetz F, Grischke EM, Fasching PA. Breast cancer treatment with everolimus and exemestane for ER+ women: results of the first interim analysis of the noninterventional trial BRAWO. Ann Oncol. 2014;25(Supplement 5):v1–41.

    Google Scholar 

  69. Bachelot T, Bourgier C, Cropet C, Ray-Coquard I, Ferrero JM, Freyer G, et al. Randomized phase II trial of everolimus in combination with tamoxifen in patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative metastatic breast cancer with prior exposure to aromatase inhibitors: a GINECO study. J Clin Oncol Off J Am Soc Clin Oncol. 2012;30(22):2718–24. Clinical Trial, Phase II Multicenter Study Randomized Controlled Trial Research Support, Non-U.S. Gov’t.

    Article  CAS  Google Scholar 

  70. Barnett CM. Everolimus: targeted therapy on the horizon for the treatment of breast cancer. Pharmacotherapy. 2012;32(4):383–96. Research Support, Non-U.S. Gov’t Review.

    Article  CAS  PubMed  Google Scholar 

  71. Andre F, Gianni L. BOLERO-3 results: pharmacological activity or pharmacokinetic effect? – authors’ reply. Lancet Oncol. 2014;15(8):e304–5. Comment Letter.

    Article  PubMed  Google Scholar 

  72. Baselga J, Semiglazov V, van Dam P, Manikhas A, Bellet M, Mayordomo J, et al. Phase II randomized study of neoadjuvant everolimus plus letrozole compared with placebo plus letrozole in patients with estrogen receptor-positive breast cancer. J Clin Oncol Off J Am Soc Clin Oncol. 2009;27(16):2630–7. Clinical Trial, Phase II Multicenter Study Randomized Controlled Trial Research Support, Non-U.S. Gov’t.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Medical Oncology, Tulay Aktaş Oncology Hospital, Ege University Medical Faculty, Kazım Dirik Mahallesi, Bornova, Izmir, 35040, Turkey

    Burcu Cakar MD & Erdem Göker MD

  2. Medical Oncology Unit, Yunus Emre State Hospital Tepebasi, Eskisehir, Turkey

    Burcu Cakar MD

Authors
  1. Burcu Cakar MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Erdem Göker MD
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Erdem Göker MD .

Editor information

Editors and Affiliations

  1. Inst of Oncology,Ist Tıp Fak, Istanbul University, Istanbul, Turkey

    Adnan Aydiner

  2. General Surgery, Istanbul Univ Istanbul Fac of Med, Istanbul, Turkey

    Abdullah İgci

  3. Breast Surgery,, Magee-Womens Hospital, Pittsburg, USA

    Atilla Soran

Rights and permissions

Reprints and permissions

Copyright information

© 2016 Springer International Publishing Switzerland

About this chapter

Cite this chapter

Cakar, B., Göker, E. (2016). Tyrosine Kinase Inhibitors. In: Aydiner, A., İgci, A., Soran, A. (eds) Breast Disease. Springer, Cham. https://doi.org/10.1007/978-3-319-26012-9_36

Download citation

  • DOI: https://doi.org/10.1007/978-3-319-26012-9_36

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-319-26010-5

  • Online ISBN: 978-3-319-26012-9

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation