The emergence of targeted therapy for HER2-low triple-negative breast cancer: a review of fam-trastuzumab deruxtecan

Expert Rev Anticancer Ther. 2023 Jul-Dec;23(10):1061-1069. doi: 10.1080/14737140.2023.2257885. Epub 2023 Oct 26.


Introduction: Metastatic triple-negative breast cancer (TNBC) is an aggressive sub-type of breast cancer. Despite recent advances, metastatic TNBC remains difficult to treat with limited targeted treatment options. Fam-trastuzumab deruxtecan (T-DXd), is a novel antibody-drug conjugate (ADC) targeting human epidermal growth factor receptor 2 (HER2) and is composed of a unique linker bound to the topoisomerase I inhibitor DXd. T-DXd has significant anti-tumor activity in patients with HER2-low TNBC.

Areas covered: This review reports on the mechanism, pre-clinical/clinical studies, efficacy, and tolerability of T-DXd. A literature search was conducted via PubMed using keywords such as 'fam-trastuzumab deruxtecan,' 'Enhertu,' and 'HER2-low cancers.'

Expert opinion: The Phase III Destiny-Breast04 Trial showed benefit in progression-free and overall survival in patients with HER2-low metastatic breast cancers treated with T-DXd compared to treatment of physician's choice chemotherapy. T-DXd is the first pharmaceutical to effectively target a HER2-low population with clinically meaningful efficacy in patients with HER2-low TNBC. Compared to chemotherapy, T-DXd has a similar safety profile, with the additional need for close monitoring for interstitial lung disease. Given the clinical activity of T-DXd in TNBC, it is likely there will be continued efforts to refine HER2-low diagnostics and to develop additional ADCs with other protein targets.

Keywords: Antibody-drug conjugate (ADC); fam-trastuzumab deruxtecan (T-DXd); human epidermal growth factor receptor 2 (HER2)-low; topoisomerase I; triple-negative breast cancer (TNBC).

Publication types

  • Review

MeSH terms

  • Breast Neoplasms* / drug therapy
  • Camptothecin / pharmacology
  • Female
  • Humans
  • Immunoconjugates* / adverse effects
  • Receptor, ErbB-2
  • Trastuzumab
  • Triple Negative Breast Neoplasms* / drug therapy


  • trastuzumab deruxtecan
  • Trastuzumab
  • Immunoconjugates
  • Camptothecin
  • Receptor, ErbB-2