CC BY-NC-ND 4.0 · Indian J Med Paediatr Oncol 2021; 42(04): 370-375
DOI: 10.1055/s-0041-1731861
How I Treat

How We Treat HER2-Positive Metastatic Breast Cancer

Ashok S. Komaranchath
1   Department of Oncology, Aster Medcity, Kochi, Kerala, India
,
Aju Mathew
2   Department of Oncology, MOSC Medical College, Kolenchery, Kerala, India
3   Department of Internal Medicine, Markey Cancer Center, University of Kentucky, Lexington, Kentucky, United States
› Author Affiliations

Introduction

Overexpression of the human epidermal growth factor receptor-2 (HER2), or amplification of the HER2 gene, is seen in approximately 15 to 25% of all breast cancer patients.[1] Real-world data from hospital-based cohorts estimated a prevalence of 23%.[2] Far more patients in India present with advanced disease when compared with high-income countries. In this narrative review, we describe the current landscape of HER2 targeting. We focus on how we treat HER2-positive metastatic breast cancer (MBC).



Publication History

Article published online:
26 November 2021

© 2021. Indian Society of Medical and Paediatric Oncology. This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial-License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).

Thieme Medical and Scientific Publishers Private Ltd.
A-12, Second Floor, Sector -2, NOIDA -201301, India

 
  • References

  • 1 Wolff AC, Hammond MEH, Hicks DG. et al American Society of Clinical Oncology; College of American Pathologists. Recommendations for human epidermal growth factor receptor 2 testing in breast cancer: American Society of Clinical Oncology/College of American Pathologists clinical practice guideline update. J Clin Oncol 2013; 31 (31) 3997-4013
  • 2 Lux MP, Nabieva N, Hartkopf AD. et al Therapy landscape in patients with metastatic HER2-positive breast cancer: data from the PRAEGNANT real-world breast cancer registry. Cancers (Basel) 2018; 11 (01) 10
  • 3 Swain SM, Baselga J, Kim SB. et al CLEOPATRA Study Group. Pertuzumab, trastuzumab, and docetaxel in HER2-positive metastatic breast cancer. N Engl J Med 2015; 372 (08) 724-734
  • 4 Vici P, Pizzuti L, Sperduti I. et al “Triple positive” early breast cancer: an observational multicenter retrospective analysis of outcome. Oncotarget 2016; 7 (14) 17932-17944
  • 5 Iancu G, Vasile D, Iancu RC, DaviŢoiu DV. “Triple positive” breast cancer - a novel category?. Rom J Morphol Embryol 2017; 58 (01) 21-26
  • 6 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 (01) 25-32
  • 7 Geyer CE, Forster J, Lindquist D. et al Lapatinib plus capecitabine for HER2-positive advanced breast cancer. N Engl J Med 2006; 355 (26) 2733-2743
  • 8 Verma S, Miles D, Gianni L. et al EMILIA Study Group. Trastuzumab emtansine for HER2-positive advanced breast cancer. N Engl J Med 2012; 367 (19) 1783-1791
  • 9 von Minckwitz G, Schwedler K, Schmidt M. et al GBG 26/BIG 03-05 study group and participating investigators. Trastuzumab beyond progression: overall survival analysis of the GBG 26/BIG 3-05 phase III study in HER2-positive breast cancer. Eur J Cancer 2011; 47 (15) 2273-2281
  • 10 Blackwell KL, Burstein HJ, Storniolo AM. 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 2012; 30 (21) 2585-2592
  • 11 Saura C, Oliveira M, Feng YH. et al NALA Investigators. Neratinib plus capecitabine versus lapatinib plus capecitabine in HER2-positive metastatic breast cancer previously treated with ≥ 2 HER2-directed regimens: phase III NALA trial. J Clin Oncol 2020; 38 (27) 3138-3149
  • 12 Murthy RK, Loi S, Okines A. et al Tucatinib, trastuzumab, and capecitabine for HER2-positive metastatic breast cancer. N Engl J Med 2020; 382 (07) 597-609
  • 13 Modi S, Saura C, Yamashita T. et al DESTINY-Breast01 Investigators. Trastuzumab deruxtecan in previously treated HER2-positive breast cancer. N Engl J Med 2020; 382 (07) 610-621
  • 14 Earl HM, Hiller L, Vallier AL. et al PERSEPHONE Steering Committee and Trial Investigators. 6 versus 12 months of adjuvant trastuzumab for HER2-positive early breast cancer (PERSEPHONE): 4-year disease-free survival results of a randomised phase 3 non-inferiority trial. Lancet 2019; 393 (10191) 2599-2612
  • 15 Purmonen TT, Pänkäläinen E, Turunen JH, Asseburg C, Martikainen JA. Short-course adjuvant trastuzumab therapy in early stage breast cancer in Finland: cost-effectiveness and value of information analysis based on the 5-year follow-up results of the FinHer Trial. Acta Oncol 2011; 50 (03) 344-352
  • 16 André F, O’Regan R, Ozguroglu M. et al Everolimus for women with trastuzumab-resistant, HER2-positive, advanced breast cancer (BOLERO-3): a randomised, double-blind, placebo-controlled phase 3 trial. Lancet Oncol 2014; 15 (06) 580-591
  • 17 Krop IE, Kim SB, González-Martín A. et al TH3RESA study collaborators. 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 (07) 689-699
  • 18 Johnston SRD, Hegg R, Im SA. et al Phase III, randomized study of dual human epidermal growth factor receptor 2 (HER2) blockade with lapatinib plus trastuzumab in combination with an aromatase inhibitor in postmenopausal women with HER2-positive, hormone receptor-positive metastatic breast cancer: updated results of ALTERNATIVE. J Clin Oncol 2021; 39 (01) 79-89
  • 19 Tolaney SM, Wardley AM, Zambelli S. et al Abemaciclib plus trastuzumab with or without fulvestrant versus trastuzumab plus standard-of-care chemotherapy in women with hormone receptor-positive, HER2-positive advanced breast cancer (monarcHER): a randomised, open-label, phase 2 trial. Lancet Oncol 2020; 21 (06) 763-775
  • 20 Chan A, Delaloge S, Holmes FA. et al ExteNET Study Group. Neratinib after trastuzumab-based adjuvant therapy in patients with HER2-positive breast cancer (ExteNET): a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol 2016; 17 (03) 367-377
  • 21 Kaufman B, Mackey JR, Clemens MR. 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 2009; 27 (33) 5529-5537
  • 22 Huober J, Fasching P, Paepke S. et al Letrozole in combination with trastuzumab is superior to letrozole monotherapy as first line treatment in patients with hormone-receptor-positive, HER2-positive metastatic breast cancer (MBC) – results of the eLEcTRA trial. Cancer Res 2009; 69 (24, suppl) ;doi: DOI: 10.1158/0008-5472.SABCS-09-4094.
  • 23 Johnston S, Pippen J Jr, Pivot X. 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 2009; 27 (33) 5538-5546
  • 24 Musolino A, Naldi N, Bortesi B. et al Immunoglobulin G fragment C receptor polymorphisms and clinical efficacy of trastuzumab-based therapy in patients with HER-2/neu-positive metastatic breast cancer. J Clin Oncol 2008; 26 (11) 1789-1796
  • 25 Perez EA, Thompson EA, Ballman KV. et al Genomic analysis reveals that immune function genes are strongly linked to clinical outcome in the North Central Cancer Treatment Group n9831 Adjuvant Trastuzumab Trial. J Clin Oncol 2015; 33 (07) 701-708
  • 26 Hou Y, Nitta H, Wei L. et al PD-L1 expression and CD8-positive T cells are associated with favorable survival in HER2-positive invasive breast cancer. Breast J 2018; 24 (06) 911-919
  • 27 Salgado R, Denkert C, Campbell C. et al Tumor-infiltrating lymphocytes and associations with pathological complete response and event-free survival in HER2-positive early-stage breast cancer treated with lapatinib and trastuzumab: a secondary analysis of the NeoALTTO trial. JAMA Oncol 2015; 1 (04) 448-454
  • 28 Stanton SE, Disis ML. Clinical significance of tumor-infiltrating lymphocytes in breast cancer. J Immunother Cancer 2016; 4: 59
  • 29 Loi S, Giobbie-Hurder A, Gombos A. et al International Breast Cancer Study Group and the Breast International Group. Pembrolizumab plus trastuzumab in trastuzumab-resistant, advanced, HER2-positive breast cancer (PANACEA): a single-arm, multicentre, phase 1b-2 trial. Lancet Oncol 2019; 20 (03) 371-382
  • 30 Emens LA, Esteva F, Beresford M. et al Results from KATE2, a randomized phase 2 study of atezolizumab (atezo) + trastuzumab emtansine (T-DM1) vs placebo (pbo)+T-DM1 in previously treated HER2+ advanced breast cancer (BC). Cancer Res 2019; 79 (Suppl. 04) PD3-01
  • 31 A randomized, phase ii study comparing trastuzumab and vinorelbine in combination with avelumab or avelumab and utomilumab (41BB/CD137 Agonist), in patients With HER2-positive metastatic breast cancer who have progressed on prior trastuzumab and pertuzumab. https://clinicaltrials.gov/ct2/show/NCT03414658.
  • 32 Jackisch C, Stroyakovskiy D, Pivot X. et al Subcutaneous vs intravenous trastuzumab for patients with ERBB2-positive early breast cancer: final analysis of the HannaH phase 3 randomized clinical trial. JAMA Oncol 2019; 5 (05) e190339
  • 33 Zagouri F, Sergentanis TN, Bartsch R. et al Intrathecal administration of trastuzumab for the treatment of meningeal carcinomatosis in HER2-positive metastatic breast cancer: a systematic review and pooled analysis. Breast Cancer Res Treat 2013; 139 (01) 13-22