Circulating HER2 DNA after trastuzumab treatment predicts survival and response in breast cancer
Boe S Sorensen1, Lise S Mortensen, Jørn Andersen
1Department of Clinical Biochemistry, Aarhus University Hospital, Norrebrogade 44, DK 8000 Aarhus C, Denmark. boesoere@rm.dk
Background:
Only a subset of breast cancer patients responds to the HER2 inhibitor trastuzumab, and methods to identify responders are needed.
Patients And Methods:
We studied 28 patients with metastatic breast cancer that had amplified human epidermal growth factor receptor 2 (HER2) genes in their primary tumour and were treated with a combination of trastuzumab and chemotherapy. Plasma was collected and amplification of the HER2 gene in circulating DNA and the amounts of the extracellular domain (ECD) of HER2 were measured just before first treatment (n=28) and just before second treatment three weeks later (HER2 DNA (n=22), HER2 ECD (n=23)).
Results:
Pre-treatment levels of HER2 gene amplification and HER2 ECD did not correlate to clinical parameters. However, 9 out of 22 patients had a more than a 14% (2 x SD) reduction in HER2 gene amplification following treatment and showed improved response (p=0.02), and overall survival (p=0.05). HER2 ECD kinetics did not correlate to clinical data.
Conclusion:
We suggest that a decrease in HER2 gene amplification in the plasma predicts a more favourable response to trastuzumab.
Insights
A decrease in plasma HER2 gene amplification predicts better response to trastuzumab in breast cancer patients. This finding aids in identifying patients likely to benefit from HER2-targeted therapy.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Identifying responders to trastuzumab therapy is crucial for HER2-positive breast cancer treatment.
- Current methods for predicting trastuzumab response are limited.
Purpose of the Study:
- To investigate the utility of circulating tumor DNA (ctDNA) HER2 gene amplification and HER2 extracellular domain (ECD) as predictive biomarkers for trastuzumab response.
- To correlate pre-treatment and on-treatment levels of these markers with clinical outcomes.
Main Methods:
- Studied 28 patients with metastatic breast cancer and HER2 gene amplification.
- Measured plasma HER2 DNA amplification and HER2 ECD before and during trastuzumab plus chemotherapy treatment.
- Analyzed correlation between marker levels and clinical response, including overall survival.
Main Results:
- Pre-treatment HER2 DNA amplification and HER2 ECD did not correlate with clinical parameters.
- A reduction of over 14% in plasma HER2 gene amplification after treatment predicted improved response (p=0.02) and overall survival (p=0.05).
- HER2 ECD kinetics did not correlate with clinical data.
Conclusions:
- A decrease in plasma HER2 gene amplification is a promising predictive biomarker for trastuzumab efficacy in HER2-positive breast cancer.
- This finding may help personalize treatment strategies for breast cancer patients receiving HER2-targeted therapy.
