Ultrasensitive circulating tumor DNA detection improves prognostication in triple-negative breast cancer postneoadjuvant therapy

BACKGROUND: Current treatment guidelines for patients diagnosed with stage II to III triple-negative breast cancer (TNBC) rely on the use of neoadjuvant therapy (NAT). A critical unmet need is a sensitive test that can inform the presence of distant micrometastases to help personalize postneoadjuvant systemic therapy beyond pathological complete response (pCR). PATIENTS AND METHODS: In this study, 286 plasma samples from 86 patients from the SCANDARE study were retrospectively analyzed for circulating tumor DNA (ctDNA) at three presurgical timepoints: baseline, during and post-NAT, and during postsurgical follow-up, when available, using an ultrasensitive, tumor-informed, whole-genome-based assay. RESULTS: After a median follow-up of 5.1 years, 15 patients (17.4%) had developed distant metastases, and 19 patients (22.1%) died; 100% of pretreatment baseline plasma samples were positive for detected ctDNA, and the majority of ctDNA detections during and post-NAT, presurgery, were at ultrasensitive (