Oncology Today with Dr Neil Love Breast Cancer — 5-Minute Journal Club Issue 2 with Dr Lajos Pusztai: Current and Future Role of Tumor-Informed Circulating Tumor DNA Assays
Mar 18, 2026
Dr Lajos Pusztai, a Yale medical oncologist specializing in breast cancer and ctDNA research, walks through trials and technologies shaping tumor-informed circulating tumor DNA testing. He covers the DARE randomized trial and real-world adoption, ctDNA-guided de-escalation strategies, Signatera whole-genome updates, stage/subtype differences in detection, and uses in neoadjuvant and metastatic monitoring.
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Baseline ctDNA Varies By Stage And Subtype
- Baseline ctDNA positivity correlates with stage and subtype: highest in triple-negative, then HER2-positive, lowest in ER-positive.
- Triple-negative stage 2/3 tumors show baseline ctDNA positivity around 80–90%, often clearing during neoadjuvant therapy.
Solid Tumor MRD Requires Multiplex Personalization
- Solid tumor ctDNA assays use multiplexed personalized targets unlike hematologic MRD which often tracks a single pathognomonic lesion.
- Multiplexing lets Signatera monitor multiple tumor-specific variants because breast cancer lacks one universal marker.
Clear Definitions For MRD Molecular Relapse And Progression
- Define terminology: MRD is tumor DNA after curative therapy; molecular relapse is ctDNA positivity during follow-up; molecular progression refers to acquired resistance markers like ESR1 before imaging progression.
- Serena-6 assessed molecular progression via ESR1 mutation emergence rather than classic MRD.