Journal of Modern OncologyJournal of Modern Oncology1815-14341815-1442LLC Obyedinennaya Redaktsiya27015Research ArticleNeoadjuvant systemic therapy of HER2-positive breast cancerFrolovaM Adrfrolova@yandex.ruN.N.Blokhin Russian Cancer Research Center of the Ministry of Health of the Russian Federation15122015174222509042020Copyright © 2015, Consilium Medicum2015HER2 overexpression is evaluated in 15-20% of breast tumors and associated with aggressive type of the disease. Introduction of trastuzumab in clinical practice significantly improve the prognosis of patients with metastatic and early HER2-positive breast cancer. However, up to 40% of patients have a resistance to trastuzumab therapy (de novo or acquired resistance). Dual anti-HER2 blockade of trastuzumab in combination with other anti-HER2 targeted agents is more effective then trastuzumab monotherapy. Neoadjuvant systemic therapy has become very useful in early breast cancer and serves as a model for research of new antitumor agents, treatment regimens and predictive biomarkers. In current review the most important recent neoadjuvant trials in HER2-positive breast cancer and their impact on clinical practice are being analysed.HER2breast cancerneoadjuvant therapyHER2trastuzumablapatinibpertuzumabрак молочной железынеоадъювантная терапиятрастузумаблапатинибпертузумаб[Cortazar P, Zhang L, Untch M et al. Pathological complete response and long - term clinical benefi t in breast cancer: the CTNeoBC pooled analysis. Lancet 2014; 384: 164-72.][Gianni L, Eiermann W, Semiglazov V et al. Neoadjuvant and adjuvant trastuzumab in patients with HER2-positive locally advanced breast cancer (NOAH): follow - up of a randomised controlled superiority trial with a parallel HER2-negative cohort. Lancet Oncol 2014; 15: 640-7.][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: 633-40.][De Azambuja E, Holmes A.P, Piccart-Gebhart M et al. Lapatinib with trastuzumab for HER2-positive early breast cancer (NeoALTTO): survival outcomes of a randomised, open - label, multicentre, phase 3 trial and their association with pathological complete response. Lancet Oncol 2014; 15: 1137-46.][Piccart-Gebhart M, Holmes E, Baselga J et al. Adjuvant Lapatinib and Trastuzumab for Early Human Epidermal Growth Factor Receptor 2-Positive Breast Cancer: Results From the Randomized Phase III Adjuvant Lapatinib and/or Trastuzumab Treatment Optimization Trial. Published online ahead of print at www.jco.org on November 23, 2015.][De Michele A, Yee D, Berry D.A et al. The neoadjuvant model is still the future for drug development in breast cancer. Clin Cancer Res 2015; 21 (13): 2911-5.][Gianni L, Pienkowski T, Im Y.H et al. Effi cacy and safety of neoadjuvant pertuzumab and trastuzumab in women with locally advanced, infl ammatory, or early HER2-positive breast cancer (NeoSpHERe): a randomised multicentre, open - label, phase 2 trial. Lancet Oncol 2012; 13: 25-32.][Gianni L, Pienkowski T, Im Y.H et al. Five - year analysis of the phase II NeoSpHERe trial evaluating four cycles of neoadjuvant docetaxel (D) and/or trastuzumab (T) and/or pertuzumab (P). JCO May 2015; 33 (15), Suppl. 505.][Schneeweiss A, Chia S, Hickish T et al. Pertuzumab plus trastuzumab in combination with standard neoadjuvant anthracycline - containing and anthracycline - free chemotHERapy regimens in patients with HER2-positive early breast cancer: a randomized phase II cardiac safety study (TRYPHAENA). Ann Oncol 2013; 24: 2278-84.][Rimawi M.F, Niravath P.A, Wang T et al. TBCRC023: A randomized multicenter phase II neoadjuvant trial of lapatinib plus trastuzumab, with endcorine tHERapy and without chemotHERapy, for 12 vs. 24 weeks in patients with HER2 overexpressing breast cancer. SABCS 2014; Abstr S6-02.][Harbeck N, Gluz O, Christgen M et al. Final analysis of WSG-ADAPT HER2+/HR+ phase II trial: Efficacy, safety, and predictive markers for 12-weeks of neoadjuvant TDM1 with or without endocrine tHERapy versus trastuzumab+endocrine tHERapy in HER2-positive hormone - receptor - positive early breast cancer. SABCS 2015; Abstr S5-03.]