Dynamic ctDNA tracking stratifies relapse risk for triple negative breast cancer patients receiving neoadjuvant chemotherapy

Early Triple negative breast cancer (eTNBC) is the subtype with the worst outcome. Circulating tumor DNA (ctDNA) is shown to predict the prognosis of breast cancer, but its utility in eTNBC remains unclear. 130 stage II-III female eTNBC patients receiving neoadjuvant chemotherapy (NAC) have been enrolled prospectively and subjected to ctDNA analysis. ctDNA at post-NAC (pre-surgery) and post-surgery, but not at baseline, is associated with worse prognosis. A threshold of 1.1% maximum variant allele frequency at baseline stratifies patients with different relapse risk, which is validated internally and externally. A systemic tumor burden model integrating baseline and post-surgery ctDNA is independently prognostic (p = 0.022). Combining systemic tumor burden with pathologic response identifies a highly curable subgroup and a subgroup of high-risk eTNBC patients. ctDNA surveillance during follow-up identifies patients with high relapse risk. In conclusion, systemic ctDNA analysis demonstrates the utility of a systemic tumor burden model of ctDNA in risk stratification of eTNBC patients, which may guide future treatment escalation or de-escalation trials.