open access

Vol 14, No 1 (2018)
Review paper
Published online: 2018-02-28
Get Citation

Dual HER2 blockade in adjuvant and neoadjuvant treatment of HER2-positive breast cancer: the role of pertuzumab

Renata Duchnowska
DOI: 10.5603/OCP.2018.0008
·
Oncol Clin Pract 2018;14(1):43-47.

open access

Vol 14, No 1 (2018)
REVIEW ARTICLES
Published online: 2018-02-28

Abstract

Trastuzumab and pertuzumab belong to the group of humanised IgG1 monoclonal antibodies produced using  recombinant DNA technology. The synergism of action of both antibodies results from their different targets:  trastuzumab binds to the IV subdomain of the HER2 receptor and blocks signals independent of the ligand, while  pertuzumab binds to subdomain II of this receptor and blocks ligand-dependent signals. Adding pertuzumab to  trastuzumab and chemotherapy in pre-operative (neoadjuvant) treatment of HER2-positive breast cancer patients  increases complete pathological response rates without enhancing adverse reactions. It was also shown in patients  with breast cancer that pCR resulting from pre-operative treatment may translate into improved survival parameters 

Abstract

Trastuzumab and pertuzumab belong to the group of humanised IgG1 monoclonal antibodies produced using  recombinant DNA technology. The synergism of action of both antibodies results from their different targets:  trastuzumab binds to the IV subdomain of the HER2 receptor and blocks signals independent of the ligand, while  pertuzumab binds to subdomain II of this receptor and blocks ligand-dependent signals. Adding pertuzumab to  trastuzumab and chemotherapy in pre-operative (neoadjuvant) treatment of HER2-positive breast cancer patients  increases complete pathological response rates without enhancing adverse reactions. It was also shown in patients  with breast cancer that pCR resulting from pre-operative treatment may translate into improved survival parameters 
Get Citation

Keywords

trastuzumab, pertuzumab, perioperative therapy, breast cancer, HER2

About this article
Title

Dual HER2 blockade in adjuvant and neoadjuvant treatment of HER2-positive breast cancer: the role of pertuzumab

Journal

Oncology in Clinical Practice

Issue

Vol 14, No 1 (2018)

Article type

Review paper

Pages

43-47

Published online

2018-02-28

DOI

10.5603/OCP.2018.0008

Bibliographic record

Oncol Clin Pract 2018;14(1):43-47.

Keywords

trastuzumab
pertuzumab
perioperative therapy
breast cancer
HER2

Authors

Renata Duchnowska

References (33)
  1. Tzahar E, Waterman H, Chen X, et al. A hierarchical network of interreceptor interactions determines signal transduction by Neu differentiation factor/neuregulin and epidermal growth factor. Mol Cell Biol. 1996; 16(10): 5276–5287.
  2. Citri A, Skaria KB, Yarden Y. The deaf and the dumb: the biology of ErbB-2 and ErbB-3. Exp Cell Res. 2003; 284(1): 54–65.
  3. Franklin MC, Carey KD, Vajdos FF, et al. Insights into ErbB signaling from the structure of the ErbB2-pertuzumab complex. Cancer Cell. 2004; 5(4): 317–328.
  4. Junttila TT, Parsons K, Olsson C, et al. Superior in vivo efficacy of afucosylated trastuzumab in the treatment of HER2-amplified breast cancer. Cancer Res. 2010; 70(11): 4481–4489.
  5. Nahta R, Hung MC, Esteva FJ. The HER-2-targeting antibodies trastuzumab and pertuzumab synergistically inhibit the survival of breast cancer cells. Cancer Res. 2004; 64(7): 2343–2346.
  6. Scheuer W, Friess T, Burtscher H, et al. Strongly enhanced antitumor activity of trastuzumab and pertuzumab combination treatment on HER2-positive human xenograft tumor models. Cancer Res. 2009; 69(24): 9330–9336.
  7. Cortazar P, Zhang L, Untch M, et al. Pathological complete response and long-term clinical benefit in breast cancer: the CTNeoBC pooled analysis. Lancet. 2014; 384(9938): 164–172.
  8. www.fda.gov.
  9. www.ema.europa.eu.
  10. Curigliano G, Burstein HJ, P Winer E, et al. St. Gallen International Expert Consensus on the Primary Therapy of Early Breast Cancer 2017. De-escalating and escalating treatments for early-stage breast cancer: the St. Gallen International Expert Consensus Conference on the Primary Therapy of Early Breast Cancer 2017. Ann Oncol. 2017; 28(8): 1700–1712.
  11. Carey LA, Metzger R, Dees EC, et al. American Joint Committee on Cancer tumor-node-metastasis stage after neoadjuvant chemotherapy and breast cancer outcome. J Natl Cancer Inst. 2005; 97(15): 1137–1142.
  12. Ogston KN, Miller ID, Payne S, et al. A new histological grading system to assess response of breast cancers to primary chemotherapy: prognostic significance and survival. Breast. 2003; 12(5): 320–327.
  13. 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): 228–233.
  14. 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): 377–384.
  15. Untch M, Rezai M, Loibl S, et al. Neoadjuvant treatment with trastuzumab in HER2-positive breast cancer: results from the GeparQuattro study. J Clin Oncol. 2010; 28(12): 2024–2031.
  16. 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. The Lancet Oncology. 2014; 15(6): 640–647.
  17. 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): 869–878.
  18. Baselga J, Bradbury I, Eidtmann H, et al. NeoALTTO Study Team. Lapatinib with trastuzumab for HER2-positive early breast cancer (NeoALTTO): a randomised, open-label, multicentre, phase 3 trial. Lancet. 2012; 379(9816): 633–640.
  19. Carey LA, Berry DA, Cirrincione CT, et al. Molecular Heterogeneity and Response to Neoadjuvant Human Epidermal Growth Factor Receptor 2 Targeting in CALGB 40601, a Randomized Phase III Trial of Paclitaxel Plus Trastuzumab With or Without Lapatinib. J Clin Oncol. 2016; 34(6): 542–549.
  20. 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): 1183–1192.
  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): 1989–1995.
  22. de Azambuja E, Holmes AP, 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(10): 1137–1146.
  23. 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.
  24. Gianni L, Pienkowski T, Im YH, et al. 5-year analysis of neoadjuvant pertuzumab and trastuzumab in patients with locally advanced, inflammatory, or early-stage HER2-positive breast cancer (NeoSphere): a multicentre, open-label, phase 2 randomised trial. Lancet Oncol. 2016; 17(6): 791–800.
  25. Bianchini G, Kiermaier A, Bianchi GV, et al. Biomarker analysis of the NeoSphere study: pertuzumab, trastuzumab, and docetaxel versus trastuzumab plus docetaxel, pertuzumab plus trastuzumab, or pertuzumab plus docetaxel for the neoadjuvant treatment of HER2-positive breast cancer. Breast Cancer Res. 2017; 19(1): 16.
  26. 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(9): 2278–2284.
  27. Mauri D, Pavlidis N, Ioannidis JPA. Neoadjuvant versus adjuvant systemic treatment in breast cancer: a meta-analysis. J Natl Cancer Inst. 2005; 97(3): 188–194.
  28. Rastogi P, Anderson SJ, Bear HD, et al. Preoperative chemotherapy: updates of National Surgical Adjuvant Breast and Bowel Project Protocols B-18 and B-27. J Clin Oncol. 2008; 26(5): 778–785.
  29. Broglio KR, Quintana M, Foster M, et al. Association of Pathologic Complete Response to Neoadjuvant Therapy in HER2-Positive Breast Cancer With Long-Term Outcomes: A Meta-Analysis. JAMA Oncol. 2016; 2(6): 751–760.
  30. 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. J Clin Oncol. 2016; 34(10): 1034–1042.
  31. von Minckwitz G, Procter M, de Azambuja E, et al. APHINITY Steering Committee and Investigators. Adjuvant Pertuzumab and Trastuzumab in Early HER2-Positive Breast Cancer. N Engl J Med. 2017; 377(2): 122–131.
  32. Coates AS, Winer EP, Goldhirsch A, et al. Panel Members. Tailoring therapies--improving the management of early breast cancer: St Gallen International Expert Consensus on the Primary Therapy of Early Breast Cancer 2015. Ann Oncol. 2015; 26(8): 1533–1546.
  33. www.nice.org.uk.

Important: This website uses cookies. More >>

The cookies allow us to identify your computer and find out details about your last visit. They remembering whether you've visited the site before, so that you remain logged in - or to help us work out how many new website visitors we get each month. Most internet browsers accept cookies automatically, but you can change the settings of your browser to erase cookies or prevent automatic acceptance if you prefer.

Wydawcą serwisu jest  "Via Medica sp. z o.o." sp.k., ul. Świętokrzyska 73, 80–180 Gdańsk

tel.:+48 58 320 94 94, faks:+48 58 320 94 60, e-mail:  viamedica@viamedica.pl