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Updated: Jul 13, 2026
Next Generation Sequencing for the Detection of Actionable Mutations in Solid and Liquid Tumors
Published on: September 20, 2016
Mutational Landscape Assessed in Tumor Tissue and Circulating Tumor DNA During Treatment of Patients with
Kristian Egebjerg1, Iben Spanggaard2, Lise Barlebo Ahlborn3
1Department of Oncology, Copenhagen University Hospital, Rigshospitalet, 9, Blegdamsvej, Copenhagen, 2100, Denmark. kristian.egebjerg.02@regionh.dk.
Background:
Human epidermal growth factor receptor 2 (HER2) aberrations, such as protein overexpression and amplification of the HER2 gene (ERBB2), are well-established in breast and gastroesophageal adenocarcinomas. However, ERBB2 oncogenic variants occur in 3.5% of all solid tumors with possible therapeutic implications. This study investigates the treatment efficacy and mutational landscape of patients with ERBB2-mutated cancers receiving HER2-targeted therapy.
Methods:
Nineteen patients with refractory solid tumors harboring ERBB2 oncogenic variants were enrolled in the Copenhagen Prospective Personalized Oncology trial and received HER2-targeted treatment. Whole-exome sequencing, ctDNA analysis, and imaging were conducted at baseline, during treatment, and upon progression. Descriptive statistics were employed due to the exploratory nature of the study.
Results:
HER2-targeted treatment yielded a 37% overall response rate, a 68% disease control rate, and a median progression-free survival of 4.4 months. A tendency was observed toward higher overall response rate (60%) in patients harboring ERBB2 oncogenic variants located in the tyrosine kinase domain. Clonality of ERBB2 oncogenic variants was linked with treatment efficacy, underscoring the reduced effect when targeting subclonal mutations. Sequential ctDNA analysis of ERBB2 oncogenic variants demonstrated correlation with treatment response.
Conclusion:
In this heterogeneous cohort of patients harboring ERBB2 oncogenic variants, HER2-targeted therapy demonstrated clinical efficacy. Mutational analysis revealed the importance of clonal ERBB2 oncogenic variants and identified factors influencing treatment outcomes. Limitations include a small sample size as well as heterogeneity in treatment regimens and cancer types.
Insights
HER2-targeted therapy shows promise for ERBB2-mutated cancers, with a 37% response rate. Clonal mutations and tyrosine kinase domain variants impact treatment efficacy, highlighting the importance of mutational analysis.
Area of Science:
- Oncology
- Genetics
- Pharmacology
Background:
- HER2 (ERBB2) aberrations are common in breast and gastroesophageal cancers.
- ERBB2 oncogenic variants occur in 3.5% of solid tumors, presenting therapeutic opportunities.
- This study focuses on the efficacy of HER2-targeted therapy in ERBB2-mutated solid tumors.
Purpose of the Study:
- To investigate the treatment efficacy of HER2-targeted therapy in patients with ERBB2-mutated cancers.
- To analyze the mutational landscape of ERBB2 oncogenic variants in relation to treatment response.
- To identify factors influencing outcomes in patients receiving HER2-targeted treatment.
Main Methods:
- Nineteen patients with refractory solid tumors and ERBB2 variants were treated with HER2-targeted therapy.
- Whole-exome sequencing, ctDNA analysis, and imaging were performed at multiple time points.
- Descriptive statistics were used due to the exploratory nature of the study.
Main Results:
- HER2-targeted therapy achieved a 37% overall response rate and 68% disease control rate.
- Median progression-free survival was 4.4 months.
- Clonality of ERBB2 variants and location in the tyrosine kinase domain influenced treatment efficacy; ctDNA analysis correlated with response.
Conclusions:
- HER2-targeted therapy demonstrated clinical efficacy in a heterogeneous group of patients with ERBB2 oncogenic variants.
- Mutational analysis highlighted the significance of clonal ERBB2 variants for treatment outcomes.
- Small sample size and heterogeneity in treatments and cancer types are limitations.
