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 (<100 parts per million) levels. Ultrasensitive ctDNA detection post-NAT, presurgery was highly prognostic of distant recurrence-free interval, disease-free survival, and overall survival. Notably, ultrasensitive ctDNA detection status improved the prognostication of patients without pCR at surgery, with 94% of non-pCR patients with undetectable ctDNA post-NAT, presurgery remaining distant recurrence-free.

CONCLUSIONS

These findings highlight the potential of ctDNA to refine risk assessment in patients with early-stage TNBC and support its investigation in interventional settings to guide systemic treatment decisions.