Will Minimal Residual Disease Monitoring Be Part of Routine Surveillance?

Background: Current breast cancer (BC) surveillance is limited to the detection of local, locoregional, or contralateral recurrence. This is based on two outdated studies from the 1990s and ignores current evidence on liquid biopsies, particularly circulating tumor DNA (ctDNA).

Summary: ctDNA has been shown to be a reliable prognostic biomarker in early BC surveillance. It can be detected using a tumor-informed or tumor-agnostic approach. However, conclusive evidence for a survival benefit from ctDNA-guided follow-up, as needed for a paradigm shift in BC surveillance, is still lacking. According to current studies, the lead time, i.e., the time from biomarker detection to clinically overt relapse, can be up to several months. This stage of MRD (minimal or molecular residual disease) offers a new therapeutic window, and currently, several studies are evaluating the efficacy of treatments initiated within this therapeutic window, based on a positive biomarker finding. Liquid biopsy might also open up the possibility of de-escalating therapy in patients with a negative biomarker result.

Key messages: ctDNA detection predicts clinical breast cancer recurrence with high sensitivity and specificity. The interval between ctDNA detection and clinical recurrence is defined as lead time and represents a stage of molecular residual disease (MRD). ctDNA-based surveillance and adjuvant therapies have the potential to improve patient outcomes and are currently being evaluated in clinical trials.