Related Experiment Video
Updated: Apr 12, 2026
Polymalic Acid-based Nano Biopolymers for Targeting of Multiple Tumor Markers: An Opportunity for Personalized Medicine?
Published on: June 13, 2014
Response to dual HER2 blockade in a patient with HER3-mutant metastatic breast cancer
F-C Bidard1, C K Y Ng2, P Cottu3
1Department of Medical Oncology, Institut Curie, Paris, France Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, USA fcbidard@curie.fr.
Background:
HER3 activating mutations have been shown in preclinical models to be oncogenic and ligand-independent, but to depend on kinase-active HER2.
Patients And Methods:
Whole-exome sequencing of the primary HER2-negative breast cancer and its HER2-negative synchronous liver metastasis from a 46-year-old female revealed the presence of an activating and clonal HER3 G284R mutation.
Results:
HER2 dual blockade with trastuzumab and lapatinib as third-line therapy led to complete metabolic response in 2 weeks and confirmed radiological partial response after 8 weeks. Following the resection of the liver metastasis, the patient remains disease-free 40 weeks after initiation of the HER2 dual blockade therapy. Immunohistochemical analysis demonstrated a substantial reduction of phospho-rpS6 and phospho-AKT in the post-therapy biopsy of the liver metastasis.
Discussion:
This is the first-in-man evidence that anti-HER2 therapies are likely effective in breast cancers harboring HER3 activating mutations.
Insights
This study shows that HER2-targeted therapies can effectively treat HER3-mutated breast cancer. A patient with HER3 G284R mutation achieved a complete response to HER2 dual blockade therapy.
Area of Science:
- Oncology
- Genetics
- Molecular Biology
Background:
- Activating HER3 mutations are oncogenic and ligand-independent, relying on kinase-active HER2.
- HER2-negative breast cancer with HER3 mutations presents a therapeutic challenge.
Observation:
- A 46-year-old female with HER2-negative breast cancer and liver metastasis was found to have an activating HER3 G284R mutation.
- The mutation was identified via whole-exome sequencing of primary and metastatic tumors.
Findings:
- HER2 dual blockade with trastuzumab and lapatinib induced a complete metabolic response in 2 weeks and partial radiological response in 8 weeks.
- The patient remained disease-free for 40 weeks post-metastasis resection.
- Post-therapy biopsy showed reduced phospho-rpS6 and phospho-AKT levels.
Implications:
- This case provides the first in-human evidence of anti-HER2 therapy efficacy in HER3-mutated breast cancer.
- Targeting HER2 may be a viable strategy for HER3-mutated HER2-negative breast cancers.
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
10:27Testing Targeted Therapies in Cancer using Structural DNA Alteration Analysis and Patient-Derived Xenografts
Published on: July 25, 2020
Related Concept Videos
02:57Targeted Cancer Therapies
There are several types of targeted therapies against...
02:38Mitogens and the Cell Cycle