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Updated: Aug 31, 2026
Serum and Plasma Copy Number Detection Using Real-time PCR
Published on: December 15, 2017
CfDNA-based copy-number dynamics during anti-PD1 treatment in metastatic triple negative breast cancer
Aaron Y Lin1, Olga I Isaeva1, Teoman Deger2
1Division of Tumor Biology & Immunology, Netherlands Cancer Institute, Amsterdam, the Netherlands.
Abstract:
Cell-free DNA (cfDNA) is an emerging technology to predict and monitor response to cancer treatment, including immune checkpoint blockade (ICB). However, data on cfDNA dynamics during ICB in metastatic triple negative breast cancer (mTNBC) are limited. While most applications of cfDNA involve assays that focus on mutation detection, mTNBC and multiple other cancer types are driven by copy-number alterations (CNAs). We evaluate cfDNA-based copy-number profile abnormality (CPA) score as a potential biomarker for monitoring ICB response in mTNBC, analyzing data from 87 patients enrolled in stage 1 and stage 2 of the TONIC trial. We find significant concordance between cfDNA-based and tissue-based CNA profiles. Additionally, responders show a decrease in CPA scores upon ICB at week 6 (three cycles of nivolumab). These findings underscore the potential of cfDNA-based CNA dynamics as a non-invasive biomarker for ICB early response assessment in patients with mTNBC. The TONIC trial is registered at ClinicalTrial.gov (NCT02499367).
Insights
Cell-free DNA copy-number profile abnormality scores can non-invasively monitor immune checkpoint blockade response in metastatic triple-negative breast cancer. A decrease in these scores indicates treatment effectiveness.
Area of Science:
- Oncology
- Genomics
- Biomarkers
Background:
- Cell-free DNA (cfDNA) shows promise for monitoring cancer treatment response, particularly immune checkpoint blockade (ICB).
- Limited data exist on cfDNA dynamics during ICB in metastatic triple-negative breast cancer (mTNBC).
- Copy-number alterations (CNAs) drive mTNBC and other cancers, yet cfDNA mutation assays are more common.
Purpose of the Study:
- To evaluate cfDNA-based copy-number profile abnormality (CPA) scores as a biomarker for monitoring ICB response in mTNBC.
- To assess the concordance between cfDNA-based and tissue-based CNA profiles.
- To analyze cfDNA CPA score dynamics in relation to ICB treatment response.
Main Methods:
- Analysis of cfDNA samples from 87 patients with mTNBC in the TONIC trial (Stages 1 & 2).
- Evaluation of cfDNA-based CPA scores.
- Comparison of cfDNA CNA profiles with tissue-based CNA profiles.
- Monitoring CPA score changes at week 6 (three cycles of nivolumab).
Main Results:
- Significant concordance was observed between cfDNA-based and tissue-based CNA profiles.
- Patients responding to ICB showed a decrease in cfDNA CPA scores at week 6.
- cfDNA CPA score dynamics correlate with ICB response in mTNBC.
Conclusions:
- cfDNA-based CNA dynamics, specifically CPA scores, show potential as a non-invasive biomarker.
- This approach can aid in early response assessment for ICB in mTNBC patients.
- Further validation of cfDNA CPA scores for ICB monitoring is warranted.
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