Minimal residue disease detection in early-stage breast cancer: a review

Over the past five years, circulating tumor DNA (ctDNA) testing has emerged as a game-changer in cancer research, serving as a less invasive and highly sensitive method to monitor tumor dynamics. CtDNA testing has a wide range of potential applications in breast cancer (BC) management, including diagnosis, monitoring treatment responses, identifying resistance mutations, predicting prognosis, and detecting future relapses. In this review, we focus on the prognostic and predictive value of ctDNA testing for BC in both neoadjuvant and adjuvant settings. We also examine the rationale behind mainstream minimal residue disease (MRD) tracking methods and highlight key considerations for successful MRD testing. Clinical evidence has shown that ctDNA-based MRD testing can accurately detect molecular relapse 8-12 months before clinical relapse in early-stage BC. Compared to advanced-stage BC, detecting ctDNA in early-stage BC is more challenging and requires ultra-sensitive testing methods due to the low levels of ctDNA released into the bloodstream, particularly in post-surgical settings, after effective neoadjuvant chemotherapy, and in late adjuvant settings that require longer follow-up. Therefore, future efforts are needed to generate additional clinical evidence in these settings to support the clinical utility and widespread adoption of ctDNA-based MRD testing.