Related Experiment Video
Updated: May 31, 2025
Validated Immunochemical Assay for Comprehensive Determination of the Human Epidermal Growth Factor Receptor 2 Released from and Bound to Cells
Published on: May 9, 2025
Human Epidermal Growth Factor Receptor 2 Loss following Treatment with Trastuzumab Deruxtecan in Patients with
Mohamed A Gouda1, Amrit Gonugunta1,2, Ecaterina E Dumbrava1
1Department of Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Purpose:
Trastuzumab deruxtecan (T-DXd) is currently approved for treating metastatic breast cancer (MBC) that is HER2 positive [immunohistochemistry (IHC) score of 3+ or in situ hybridization (ISH) positivity] or HER2-low (IHC score of 1+ or IHC 2+/ISH negative), as well as for HER2-positive gastric cancer, HER2-mutant lung cancer, and HER2-overexpressing solid tumors. Given the increasing utilization of T-DXd, we sought to determine how HER2 status might change following T-DXd therapy.
Experimental Design:
We retrospectively reviewed patients with MBC who received T-DXd at the University of Texas MD Anderson Cancer Center. We included patients with paired pre- and post-treatment biopsies assessed for HER2 status using IHC.
Results:
We included 41 patients with MBC who received treatment with T-DXd and had paired pre- and post-treatment biopsies assessed for HER2 status using IHC. HER2 loss was observed in 11 patients [32.4% of 34 patients with pre-treatment HER2 expression (1+, 2+, or 3+)] following treatment with T-DXd. In addition to the 11 patients with HER2 loss, another 10 patients (29.4%) had a decrease in HER2 score after treatment with T-DXd.
Conclusions:
HER2 loss and decrease in HER2 expression are common in patients with MBC receiving treatment with T-DXd. Reevaluation of HER2 status following T-DXd treatment should be considered prior to alternate HER2-targeted therapies that require HER2 overexpression for efficacy.
Insights
Trastuzumab deruxtecan (T-DXd) treatment can cause HER2 loss or decreased expression in metastatic breast cancer patients. Reassessing HER2 status after T-DXd is crucial for guiding subsequent HER2-targeted therapies.
Area of Science:
- Oncology
- Medical Genetics
Background:
- Trastuzumab deruxtecan (T-DXd) is approved for HER2-positive and HER2-low metastatic breast cancer (MBC), HER2-positive gastric cancer, HER2-mutant lung cancer, and HER2-overexpressing solid tumors.
- The increasing use of T-DXd necessitates understanding potential changes in HER2 status during treatment.
Purpose of the Study:
- To investigate changes in HER2 expression status in patients with MBC undergoing T-DXd therapy.
- To determine the incidence of HER2 loss or downregulation after T-DXd treatment.
Main Methods:
- Retrospective review of 41 MBC patients treated with T-DXd at a single institution.
- Analysis of paired pre- and post-treatment tumor biopsies for HER2 status using immunohistochemistry (IHC).
Main Results:
- HER2 loss was observed in 11 out of 34 patients (32.4%) with pre-treatment HER2 expression (1+, 2+, or 3+).
- An additional 10 patients (29.4%) showed a decrease in their HER2 IHC score after T-DXd treatment.
- Overall, a significant proportion of patients experienced HER2 downregulation or loss post-T-DXd therapy.
Conclusions:
- HER2 loss and decreased HER2 expression are frequent occurrences in MBC patients treated with T-DXd.
- Re-evaluation of HER2 status after T-DXd therapy is recommended before initiating alternative HER2-targeted treatments that depend on HER2 overexpression.
More Related Videos
08:59Looking for Driver Pathways of Acquired Resistance to Targeted Therapy: Drug Resistant Subclone Generation and Sensitivity Restoring by Gene Knock-down
Published on: December 11, 2017
13:59High-Content Screening Assay for the Identification of Antibody-Dependent Cellular Cytotoxicity Modifying Compounds
Published on: August 18, 2023
Related Concept Videos
02:38Mitogens and the Cell Cycle
02:57Targeted Cancer Therapies
There are several types of targeted therapies against...
02:30Metastasis
Epithelial-to-Mesenchymal Transition
The epithelial-to-mesenchymal transition or EMT is a developmental process commonly observed in wound healing, embryogenesis, and cancer metastasis. EMT is induced by transforming growth factor-beta (TGF-β) or receptor tyrosine kinase (RTK) ligands, which further...
01:00Enzyme-linked Receptors
Neurotrophin (NT) receptors are a family of RTKs, including trkA, trkB, and trkC (tropomyosin-related kinase) receptors. TrkA is specific for nerve growth factor (NGF), neurotrophin-6, and neurotrophin-7. TrkB binds...
02:56Treatment Resistant Cancers
01:15Receptor Downregulation in MVBs
The EGFR can initiate signaling pathways that lead to cell proliferation, migration, and differentiation. Overexpression of EGFR stimulates cells to proliferate. Excessive EGFR...