Clinical Validation of Digital PCR-based ctDNA detection for risk stratification in residual triple negative breast cancer: TRICIA trial results

Abstract Purpose: Triple-negative breast cancer (TNBC) patients who have residual tumor at surgery (non-pathological 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 or not 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/pre-operative (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 3 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 ddPCR assays in an academic hospital-based context can reliably identify a very low-risk group of non-pCR TNBC patients.