CfDNA-based copy-number dynamics during anti-PD1 treatment in metastatic triple negative breast cancer.

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).