Advances in therapy of breast cancer: overexpression and therapeutic implications of targeting human epidermal growth factor receptors
DOI:
https://doi.org/10.18203/2319-2003.ijbcp20191612Keywords:
Breast cancer, Human epidermal growth factor receptor 2 (HER2), Lapatinib, TrastuzumabAbstract
The human epidermal growth factor receptor 2 (HER2) ERbb2 gene is amplified in approximately 25% of breast cancers. Characteristics of HER2-amplified tumors include increased proliferation rates and a propensity for distant metastasis. The discovery of overexpression of HER2 in a subset of breast cancers was an important milestone in our understanding of the biology of the disease. This paved the way for the discovery of trastuzumab, a humanized monoclonal antibody targeting HER2. Trastuzumab is the foundation of treatment of HER2- positive breast cancers, demonstrating dramatic responses in patients with metastatic disease. Recent advances in our understanding of the interaction between HER2 and other members of the epidermal growth factor receptor family have led to the identification of newer agents, resulting in the expansion of the clinical armamentarium of available agents for the treatment of HER2-positive tumors. The biology of the ERbb receptor family, the use of HER2-targeted agents in breast cancer, and the advances in anti-HER2 agents that are currently in clinical development are reviewed here.
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References
Hynes NE, Lane HA. ERBB receptors and cancer; the complexity of targeted inhibitors. Nat Rev Cancer. 2005;5(5):341-54. [PubMed]
Yarden Y, Sliwkowski MX. Untangling the ErbB signalling network. Nat Rev Mol Cell Biol. 2001;2(2):127-37. [PubMed]
Molecular biology of human epidermal receptors, signaling pathways and targeted therapy against cancers: New evidences and old challenges - Scientific Figure on ResearchGate. Available at: https://www.researchgate.net/figure/General-arrangement-of-receptors-HER1-2-3-4-and-their-natural-soluble-ligands-The_fig1_318444447 [accessed 30 Mar, 2019]
Arpino G, Wiechmann L, Osborne CK, Schiff R. Crosstalk between the estrogen receptor and the HER tyrosine kinase receptor family: molecular mechanism and clinical implications for endocrine therapy resistance. Endocr Rev. 2008;29(2):217-33. [PMC free article] [PubMed]
Prat A, Baselga J. The role of hormonal therapy in the management of hormonal-receptor-positive breast cancer with co-expression of HER2. Nat Clin Pract Oncol. 2008;5(9):531-42. [PubMed]
Musgrove EA, Sutherland RL. Biological determinants of endocrine resistance in breast cancer. Nat Rev Cancer. 2009;9(9):631-43. [PubMed]
Romond EH, Perez EA, Bryant J, Suman VJ, Geyer Jr CE, Davidson NE, et al. Trastuzumab plus adjuvant chemotherapy for operable HER2-positive breast cancer. New Engl J Medi. 2005 Oct 20;353(16):1673-84.
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. New Engl J Medi. 2005 Oct 20;353(16):1659-72.
Slamon D, Eiermann W, Robert N, Pienkowski T, Martin M, Rolski J, 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. Breast Cancer Res Treat. 2005;94(1):S1.
Joensuu H, Kellokumpu-Lehtinen PL, Bono P, Alanko T, Kataja V, Asola R, et al. Adjuvant docetaxel or vinorelbine with or without trastuzumab for breast cancer. New Engl J Medi. 2006 Feb 23;354(8):809-20.
Slamon DJ, Leyland-Jones B, Shak S, Fuchs H, Paton V, Bajamonde A, et al. Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2. New Engl J Medi. 2001 Mar 15;344(11):783-92.
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 Apr 20;27(12):1999-2006.
Slamon D, Eiermann W, Robert N, Pienkowski T, Martin M, Press M, et al. Adjuvant trastuzumab in HER2-positive breast cancer. New Engl J Medi. 2011 Oct 6;365(14):1273-83.
Zeglinski M, Ludke A, Jassal DS, Singal PK. Trastuzumab-induced cardiac dysfunction: a ‘dualhit’. Exp Clin Cardiol. 2011; 16(3):70-4.
Perez EA, Suman VJ, Davidson NE, Sledge GW, Kaufman PA, Hudis CA, 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. Journal of clinical oncology: Off J Americ Socie Clin Oncol. 2008 Mar 10;26(8):1231.
Vu T, Claret FX. Trastuzumab: updated mechanisms of action and resistance in breast cancer. Front Oncol. 2012;2:62.
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.
Pivot X, Romieu G, Debled M, Pierga JY, Kerbrat P, Bachelot T. PHARE randomized trial final results comparing 6 to 12 months of trastuzumab in adjuvant early breast cancer. In San Antonio Breast Cancer Symposium 2018 Dec 4.
Geyer CE, Forster J, Lindquist D, Chan S, Romieu CG, Pienkowski T, et al. Lapatinib plus capecitabine for HER2-positive advanced breast cancer. New Engl J Medi. 2006 Dec 28;355(26):2733-43.
Schwartzberg LS, Franco SX, Florance A, O'Rourke L, Maltzman J, Johnston S. Lapatinib plus letrozole as first-line therapy for HER-2+ hormone receptor–positive metastatic breast cancer. The oncologist. 2010 Feb 1;15(2):122-9.
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 May 10;30(14):1594-600.
Molecular Mechanisms of Cardiotoxicity Induced by ErbB Receptor Inhibitor Cancer Therapeutics - Scientific Figure on Research Gate. Available at: https://www.researchgate.net/figure/Mode-action-of-current-ErbB2-inhibitors-Trastuzumab-pertuzumab-and-lapatinib-have-a_fig2_233829203 [Accessed 30 Mar, 2019].
Verma S, Miles D, Gianni L, Krop IE, Welslau M, Baselga J, et al. Trastuzumab emtansine for HER2-positive advanced breast cancer. New Engl J Medi. 2012 Nov 8;367(19):1783-91.
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 Mar 10;28(8):1301-7.
Gnant M, Martin M, Holmes FA, Jackisch C, Chia SK, Iwata H, et al. Abstract P2-13-01: Efficacy of neratinib in hormone receptor-positive patients who initiated treatment within 1 year of completing trastuzumab-based adjuvant therapy in HER2+ early-stage breast cancer: Subgroup analyses from the phase III ExteNET trial.