Clinical Validation of Digital PCR–Based ctDNA Detection for Risk Stratification in Residual Triple-Negative Breast Cancer: TRICIA Trial Results

PURPOSE: Patients with triple-negative breast cancer (TNBC) who have residual tumor at surgery [nonpathologic complete response or (non-pCR)] after neoadjuvant chemotherapy (NAC) have a poor prognosis. In these cases, adjuvant chemotherapy with capecitabine improves disease-free survival in ∼15% of patients. Identifying those who would benefit from such additional therapy remains a critical need. EXPERIMENTAL DESIGN: In the TRICIA trial, 92 patients with non-pCR provided plasma before surgery and after NAC (T1), after surgery (T2), during adjuvant capecitabine therapy (T3), and late after surgery following completion of adjuvant treatment (T4). The sensitivity, specificity, and predictive values of a tumor-informed digital droplet-based ctDNA detection assay were measured with a median follow-up of 38 months. RESULTS: ctDNA was detected in 97% of patients before clinical relapse. We confirmed that the lack of detection of ctDNA at the post-NAC/preoperative (T1) time point is highly prognostic, with 95% distant-disease relapse-free survival. The detection of ctDNA in patients with significant residual tumor (Residual Cancer Burden 2/3) was also highly prognostic and our test performed with 100% sensitivity and 100% specificity in RCB 3 patients. We measured three time points before, during, and after capecitabine treatment and found that capecitabine treatment was associated with clearance of ctDNA in 41% of cases, and clearance was associated with good prognosis. CONCLUSIONS: These findings suggest that ctDNA testing using digital droplet PCR assays in an academic hospital-based context can reliably identify a very low-risk group of patients with non-pCR TNBC.