Current Updates in Management of HER2-Positive and HER2-Low Breast Cancer

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. https://doi.org/10.1126/science.3798106.

Article  CAS  PubMed  Google Scholar 

Guarneri V, Barbieri E, Dieci MV, Piacentini F, Conte P. Anti-HER2 neoadjuvant and adjuvant therapies in HER2 positive breast cancer. Cancer Treat Rev. 2010;36(Suppl 3):S62–6. https://doi.org/10.1016/S0305-7372(10)70022-0.

Article  CAS  PubMed  Google Scholar 

Klapper LN, Glathe S, Vaisman N, Hynes NE, Andrews GC, Sela M, et al. The ErbB-2/HER2 oncoprotein of human carcinomas may function solely as a shared coreceptor for multiple stroma-derived growth factors. Proc Natl Acad Sci U S A. 1999;96(9):4995–5000. https://doi.org/10.1073/pnas.96.9.4995.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Browne BC, O’Brien N, Duffy MJ, Crown J, O’Donovan N. HER-2 signaling and inhibition in breast cancer. Curr Cancer Drug Targets. 2009;9(3):419–38. https://doi.org/10.2174/156800909788166484.

Article  CAS  PubMed  Google Scholar 

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. N Engl J Med. 2001;344(11):783–92. https://doi.org/10.1056/NEJM200103153441101.

Article  CAS  PubMed  Google Scholar 

Triantafyllidi E, Triantafillidis JK. Systematic review on the use of biosimilars of trastuzumab in HER2+ breast cancer. Biomedicines. 2022;10(8). https://doi.org/10.3390/biomedicines10082045.

Pivot X, Bondarenko I, Nowecki Z, Dvorkin M, Trishkina E, Ahn JH, et al. Phase III, randomized, double-blind study comparing the efficacy, safety, and immunogenicity of SB3 (trastuzumab biosimilar) and reference trastuzumab in patients treated with neoadjuvant therapy for human epidermal growth factor receptor 2-positive early breast cancer. J Clin Oncol. 2018;36(10):968–74. https://doi.org/10.1200/JCO.2017.74.0126.

Article  CAS  PubMed  Google Scholar 

Scheuer W, Friess T, Burtscher H, Bossenmaier B, Endl J, Hasmann M. Strongly enhanced antitumor activity of trastuzumab and pertuzumab combination treatment on HER2-positive human xenograft tumor models. Cancer Res. 2009;69(24):9330–6. https://doi.org/10.1158/0008-5472.CAN-08-4597.

Article  CAS  PubMed  Google Scholar 

Swain SM, Baselga J, Kim SB, Ro J, Semiglazov V, Campone M, et al. Pertuzumab, trastuzumab, and docetaxel in HER2-positive metastatic breast cancer. N Engl J Med. 2015;372(8):724–34. https://doi.org/10.1056/NEJMoa1413513.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Swain SM, Miles D, Kim SB, Im YH, Im SA, Semiglazov V, et al. Pertuzumab, trastuzumab, and docetaxel for HER2-positive metastatic breast cancer (CLEOPATRA): end-of-study results from a double-blind, randomised, placebo-controlled, phase 3 study. Lancet Oncol. 2020;21(4):519–30. https://doi.org/10.1016/S1470-2045(19)30863-0.

Article  CAS  PubMed  Google Scholar 

Baselga J, Swain SM. CLEOPATRA: a phase III evaluation of pertuzumab and trastuzumab for HER2-positive metastatic breast cancer. Clin Breast Cancer. 2010;10(6):489–91. https://doi.org/10.3816/CBC.2010.n.065.

Article  PubMed  Google Scholar 

Martínez-Sáez O, Prat A. Current and future management of HER2-positive metastatic breast cancer. JCO Oncol Pract. 2021;17(10):594–604. https://doi.org/10.1200/OP.21.00172.

Article  PubMed  Google Scholar 

Sapra P, Shor B. Monoclonal antibody-based therapies in cancer: advances and challenges. Pharmacol Ther. 2013;138(3):452–69. https://doi.org/10.1016/j.pharmthera.2013.03.004.

Article  CAS  PubMed  Google Scholar 

Beck A, Goetsch L, Dumontet C, Corvaïa N. Strategies and challenges for the next generation of antibody-drug conjugates. Nat Rev Drug Discov. 2017;16(5):315–37. https://doi.org/10.1038/nrd.2016.268.

Article  CAS  PubMed  Google Scholar 

Diéras V, Miles D, Verma S, Pegram M, Welslau M, Baselga J, et al. Trastuzumab emtansine versus capecitabine plus lapatinib in patients with previously treated HER2-positive advanced breast cancer (EMILIA): a descriptive analysis of final overall survival results from a randomised, open-label, phase 3 trial. Lancet Oncol. 2017;18(6):732–42. https://doi.org/10.1016/S1470-2045(17)30312-1.

Article  PubMed  PubMed Central  Google Scholar 

Verma S, Miles D, Gianni L, Krop IE, Welslau M, Baselga J, et al. Trastuzumab emtansine for HER2-positive advanced breast cancer. N Engl J Med. 2012;367(19):1783–91. https://doi.org/10.1056/NEJMoa1209124.

Article  CAS  PubMed  PubMed Central  Google Scholar 

• Schlam I, Tolaney SM, Tarantino P. How I treat HER2-low advanced breast cancer. Breast. 2023. https://doi.org/10.1016/j.breast.2023.01.005. This is a high yield reference outlining changing landscape of HER2 low disease.

Article  PubMed  PubMed Central  Google Scholar 

Modi S, Saura C, Yamashita T, Park YH, Kim SB, Tamura K, et al. Trastuzumab deruxtecan in previously treated HER2-positive breast cancer. N Engl J Med. 2020;382(7):610–21. https://doi.org/10.1056/NEJMoa1914510.

Article  CAS  PubMed  Google Scholar 

•• Cortés J, Kim SB, Chung WP, Im SA, Park YH, Hegg R, et al. Trastuzumab deruxtecan versus trastuzumab emtansine for breast cancer. N Engl J Med. 2022;386(12):1143–54. https://doi.org/10.1056/NEJMoa2115022.This reference highlights improvement in clinical activity that is noted with fam-trastuzumab deruxtecan versus trastuzumab emtansine. This publication emphasizes how fam-trastuzumab is a preferred second line therapy for metastatic HER2 positive disease.

Article  PubMed  Google Scholar 

• Swain SM, Shastry M, Hamilton E. Targeting HER2-positive breast cancer: advances and future directions. Nat Rev Drug Discov. 2022:1–26. https://doi.org/10.1038/s41573-022-00579-0. This publication by Dr. Swain’s group provides several insights into mechanisms of resistance in HER2-driven disease and what future approaches could be high yield in understanding the pathophysiology of the disease and resistance mechanisms.

Geyer CE, Forster J, Lindquist D, Chan S, Romieu CG, Pienkowski T, et al. Lapatinib plus capecitabine for HER2-positive advanced breast cancer. N Engl J Med. 2006;355(26):2733–43. https://doi.org/10.1056/NEJMoa064320.

Article  CAS  PubMed  Google Scholar 

Gelmon KA, Boyle FM, Kaufman B, Huntsman DG, Manikhas A, Di Leo A et al. Lapatinib or trastuzumab plus taxane therapy for human epidermal growth factor receptor 2-positive advanced breast cancer: final results of NCIC CTG MA.31. J Clin Oncol. 2015;33(14):1574–83. https://doi.org/10.1200/JCO.2014.56.9590.

Murthy RK, Loi S, Okines A, Paplomata E, Hamilton E, Hurvitz SA, et al. Tucatinib, trastuzumab, and capecitabine for HER2-positive metastatic breast cancer. N Engl J Med. 2020;382(7):597–609. https://doi.org/10.1056/NEJMoa1914609.

Article  CAS  PubMed  Google Scholar 

Gianni L, Pienkowski T, Im YH, Roman L, Tseng LM, Liu MC, 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. https://doi.org/10.1016/S1470-2045(11)70336-9.

Article  CAS  PubMed  Google Scholar 

Tolaney SM, Barry WT, Dang CT, Yardley DA, Moy B, Marcom PK, et al. Adjuvant paclitaxel and trastuzumab for node-negative, HER2-positive breast cancer. N Engl J Med. 2015;372(2):134–41. https://doi.org/10.1056/NEJMoa1406281.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Tolaney SM, Guo H, Pernas S, Barry WT, Dillon DA, Ritterhouse L, et al. Seven-year follow-up analysis of adjuvant paclitaxel and trastuzumab trial for node-negative, human epidermal growth factor receptor 2-positive breast cancer. J Clin Oncol. 2019;37(22):1868–75. https://doi.org/10.1200/JCO.19.00066.

Article  CAS  PubMed  PubMed Central  Google Scholar 

von Minckwitz G, Huang CS, Mano MS, Loibl S, Mamounas EP, Untch M, et al. Trastuzumab emtansine for residual invasive HER2-positive breast cancer. N Engl J Med. 2019;380(7):617–28. https://doi.org/10.1056/NEJMoa1814017.

Article  Google Scholar 

Chan A, Moy B, Mansi J, Ejlertsen B, Holmes FA, Chia S, et al. Final efficacy results of neratinib in HER2-positive hormone receptor-positive early-stage breast cancer from the phase III ExteNET trial. Clin Breast Cancer. 2021;21(1):80-91.e7. https://doi.org/10.1016/j.clbc.2020.09.014.

Article  CAS  PubMed  Google Scholar 

Bartsch R, Berghoff AS, Furtner J, Marhold M, Bergen ES, Roider-Schur S, et al. Trastuzumab deruxtecan in HER2-positive breast cancer with brain metastases: a single-arm, phase 2 trial. Nat Med. 2022;28(9):1840–7. https://doi.org/10.1038/s41591-022-01935-8.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Tarantino P, Hamilton E, Tolaney SM, Cortes J, Morganti S, Ferraro E, et al. HER2-low breast cancer: pathological and clinical landscape. J Clin Oncol. 2020;38(17):1951–62. https://doi.org/10.1200/JCO.19.02488.

Article  CAS  PubMed  Google Scholar 

Fehrenbacher L, Cecchini RS, Geyer CE, Rastogi P, Costantino JP, Atkins JN, et al. NSABP B-47/NRG oncology phase III randomized trial comparing adjuvant chemotherapy with or without trastuzumab in high-risk invasive breast cancer negative for HER2 by FISH and with IHC 1+ or 2. J Clin Oncol. 2020;38(5):444–53. https://doi.org/10.1200/JCO.19.01455.

Article  CAS  PubMed  Google Scholar 

Modi S, Jacot W, Yamashita T, Sohn J, Vidal M, Tokunaga E, et al. Trastuzumab deruxtecan in previously treated HER2-low advanced breast cancer. N Engl J Med. 2022;387(1):9–20. https://doi.org/10.1056/NEJMoa2203690.

Article  CAS  PubMed  Google Scholar 

Manich CS, O’Shaughnessy J, Aftimos PG, van den Tweel E, Oesterholt M, Escrivá-de-Romaní SI, Tueux NQ, Tan TJ, Lim JS, Ladoire S, Armstrong A. LBA15 primary outcome of the phase III SYD985 002/TULIP trial comparing [vic-] trastuzumab duocarmazine to physician’s choice treatment in patients with pre-treated HER2-positive locally advanced or metastatic breast cancer. Annals of Oncology. 2021;32:S1288.

Article  Google Scholar 

van Ramshorst MS, van der Voort A, van Werkhoven ED, Mandjes IA, Kemper I, Dezentjé VO, et al. Neoadjuvant chemotherapy with or without anthracyclines in the presence of dual HER2 blockade for HER2-positive breast cancer (TRAIN-2): a multicentre, open-label, randomised, phase 3 trial. Lancet Oncol. 2018;19(12):1630–40. https://doi.org/10.1016/S1470-2045(18)30570-9.

Article  PubMed  Google Scholar 

von Minckwitz G, Procter M, de Azambuja E, Zardavas D, Benyunes M, Viale G, et al. Adjuvant pertuzumab and trastuzumab in early HER2-positive breast cancer. N Engl J Med. 2017;377(2):122–31. https://doi.org/10.1056/NEJMoa1703643.

Article  Google Scholar 

Comments (0)

No login
gif