Targeted Therapies

  • Radhakrishna Selvi


The most important advance in targeted therapy for breast cancer is the ability to target the estrogen receptor(ER) and human epidermal growth factor tyrosine kinase receptor 2 (HER-2) changing the outcome of disease drastically. There is a plethora of the targeted agents in breast cancer that have come up one after another in the recent times. It remains critical to choose a targeted agent keeping in mind its efficacy, biology of the disease, side effects, ideal way of using with or without chemotherapy, and guiding treatment decisions with the help of predictive biomarkers.


Breast Cancer TNBC Patient Combination Target Therapy Negative Invasive Breast Cancer Single Agent Lapatinib 
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  1. 1.
    Siegel R, Ma J, Zou Z, Jemal A. Cancer statistics. CA Cancer J Clin. 2014;64(1):9–29.PubMedCrossRefGoogle Scholar
  2. 2.
    Slamon DJ, Clark GM, Wong SG, Levin WJ, Ullrich A, McGuire WL. Human breast cancer: correlation of relapse and survival with amplification of the HER-2/neu oncogene. Science. 1987;235(4785):177–82.PubMedCrossRefGoogle Scholar
  3. 3.
    Pauletti G, Godolphin W, Press MF, Slamon DJ. Detection and quantitation of HER-2/neu gene amplification in human breast cancer archival material using fluorescence in situ hybridization. Oncogene. 1996;13(1):63–72.PubMedGoogle Scholar
  4. 4.
    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(1):16–32.CrossRefGoogle Scholar
  5. 5.
    Hudis CA. Trastuzumab–mechanism of action and use in clinical practice. N Engl J Med. 2007;357(1):39–51.PubMedCrossRefGoogle Scholar
  6. 6.
    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. 2001;344(11):783–92.PubMedCrossRefGoogle Scholar
  7. 7.
    Ignatiadis M, Desmedt C, Sotiriou C, de Azambuja E, Piccart M. HER-2 as a target for breast cancer therapy. Clin Cancer Res. 2009;15(6):1848–52.PubMedCrossRefGoogle Scholar
  8. 8.
    Goldhirsch A, Gelber RD, Piccart-Gebhart MJ, et al. 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.PubMedCrossRefGoogle Scholar
  9. 9.
    Pivot X, Romieu G, Debled M, 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 Oncol. 2013;14(8):741–8.PubMedCrossRefGoogle Scholar
  10. 10.
    Ismael G, Hegg R, Muehlbauer S, et al. Subcutaneous versus intravenous administration of (neo)adjuvant trastuzumab in patients with HER2-positive, clinical stage I-III breast cancer (HannaH study): a phase 3, open-label, multicentre, randomised trial. Lancet Oncol. 2012;13(9):869–78.PubMedCrossRefGoogle Scholar
  11. 11.
    Pivot X, Gligorov J, Muller V, et al. Preference for subcutaneous or intravenous administration of trastuzumab in patients with HER2-positive early breast cancer (PrefHer): an open-label randomised study. Lancet Oncol. 2013;14(10):962–70.PubMedCrossRefGoogle Scholar
  12. 12.
    Ewer MS, Lippman SM. Type II chemotherapy-related cardiac dysfunction: time to recognize a new entity. J Clin Oncol. 2005;23(13):2900–2.PubMedCrossRefGoogle Scholar
  13. 13.
    TYKERB(Lapatinib). package insert. glaxoSmithKline 2012. 2012.Google Scholar
  14. 14.
    Goss PE, Smith IE, O’Shaughnessy J, et al. Adjuvant lapatinib for women with early-stage HER2-positive breast cancer: a randomised, controlled, phase 3 trial. Lancet Oncol. 2013;14(1):88–96.PubMedCrossRefGoogle Scholar
  15. 15.
    E P. HER2-directed therapy 2011 breast cancer symposium. Welcome and general session VII: advances in molecular classification of breast cancer and clinical implications. 2011.Google Scholar
  16. 16.
    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;13(1):228–33.PubMedCrossRefGoogle Scholar
  17. 17.
    Gianni L, Eiermann W, Semiglazov V, 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(9712):377–84.PubMedCrossRefGoogle Scholar
  18. 18.
    Baselga J, Bradbury I, Eidtmann H, 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.PubMedCrossRefGoogle Scholar
  19. 19.
    Robidoux A, Tang G, Rastogi P, et al. Lapatinib as a component of neoadjuvant therapy for HER2-positive operable breast cancer (NSABP protocol B-41): an open-label, randomised phase 3 trial. Lancet Oncol. 2013;14(12):1183–92.PubMedCrossRefGoogle Scholar
  20. 20.
    Carey LA, Berry D, Ollila D, et al. Clinical and translational results of CALGB 40601. 2013 ASCO Annual Meeting. Abstract 500. Presented 2 June 2013.Google Scholar
  21. 21.
    Guarneri V, Frassoldati A, Bottini A, 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(16):1989–95.PubMedCrossRefGoogle Scholar
  22. 22.
    Hurvitz S, et al. Final analysis of a phase II 3-arm randomized trial of neoadjuvant trastuzumab or lapatinib or the combination of trastuzumab and lapatinib, followed by six cycles of docetaxel and carboplatin with trastuzumab and/or lapatinib in patients with HER2+ breast cancer (TRIO-US B07)presentation S1-02, San Antonio breast cancer symposium, San Antonio December 2013.Google Scholar
  23. 23.
    Untch M, Loibl S, Bischoff J, 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.PubMedCrossRefGoogle Scholar
  24. 24.
    Carey LA. Neoadjuvant trials of human epidermal growth factor receptor 2 targeting: how many drugs do we need? J Clin Oncol. 2012;30(16):1909–11.PubMedCrossRefGoogle Scholar
  25. 25.
    Baselga J, Gelmon KA, Verma S, 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(7):1138–44.PubMedCrossRefGoogle Scholar
  26. 26.
    Gianni L, Pienkowski T, Im YH, 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.PubMedCrossRefGoogle Scholar
  27. 27.
    Wagner AD, Thomssen C, Haerting J, Unverzagt S. Vascular-endothelial-growth-factor (VEGF) targeting therapies for endocrine refractory or resistant metastatic breast cancer. Cochrane Database Syst Rev. 2012;(7):CD008941.Google Scholar
  28. 28.
    O’Shaughnessy J, Romieu G, Diéras V, et al. Meta-analysis of patients with triple-negative breast cancer (TNBC) from three randomized trials of first-line bevacizumab (BV) and chemotherapy treatment for metastatic breast cancer (MBC). Proceedings of the 33rd Annual CTRC-AACR San Antonio Breast Cancer Symposium. San Antonio: AACR Philadelphia; 8–12 Dec 2010. Abstr P6-12-03 2010. 2010.Google Scholar
  29. 29.
    Brufsky AM, Hurvitz S, Perez E, et al. RIBBON-2: a randomized, double-blind, placebo-controlled, phase III trial evaluating the efficacy and safety of bevacizumab in combination with chemotherapy for second-line treatment of human epidermal growth factor receptor 2-negative metastatic breast cancer. J Clin Oncol. 2011;29(32):4286–93.PubMedCrossRefGoogle Scholar
  30. 30.
    Cameron D, Brown J, Dent R, et al. Adjuvant bevacizumab-containing therapy in triple-negative breast cancer (BEATRICE): primary results of a randomised, phase 3 trial. Lancet Oncol. 2013;14(10):933–42.PubMedCrossRefGoogle Scholar
  31. 31.
    Gerber B, Loibl S, Eidtmann H, et al. Neoadjuvant bevacizumab and anthracycline-taxane-based chemotherapy in 678 triple-negative primary breast cancers; results from the geparquinto study (GBG 44). Ann Oncol. 2013;24(12):2978–84.PubMedCrossRefGoogle Scholar
  32. 32.
    Bear HD, Tang G, Rastogi P, et al. Bevacizumab added to neoadjuvant chemotherapy for breast cancer. N Engl J Med. 2012;366(4):310–20.PubMedCentralPubMedCrossRefGoogle Scholar
  33. 33.
    Slamon DJ, et al. Primary results from BETH, a phase 3 controlled study of adjuvant chemotherapy and trastuzumab ± bevacizumab in patients with HER2-positive, node-positive or high risk node-negative breast cancer. 36th Annual San Antonio Breast Cancer Symposium (SABCS): Abstract S1-03. Presented 11 Dec 2013.Google Scholar

Copyright information

© Springer India 2015

Authors and Affiliations

  • Radhakrishna Selvi
    • 1
  1. 1.Chennai Breast CentreChennaiIndia

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