Analysis of Circulating Tumor DNA to Monitor Metastatic Breast Cancer Patients Treated with First-Line Chemotherapy (CAMELLIA Study).

e14568 Background: Our precious study indicated that the dynamic changes in circulating tumor DNA (ctDNA) could reflect changes in tumor burden. We conduct this study to validate the role of ctDNA as a therapeutic response biomarker in a larger cohort prospective phase III randomized multicenter study. Methods: In this study, we collected 292 serial ctDNA samples from 125 metastatic breast cancer patients treated with first line chemotherapy. Target-capture deep sequencing of 1021 genes was performed to detect somatic variants in ctDNA. Results: 81.4% patients had detectable ctDNA at baseline. An undetectable ctDNA at baseline was associated with a lower disease volume (p < 0.05). The commonly mutated genes were PIK3CA (35.0%), TP53 (34.2%), MLL3 (9.4%) and ESR1 (9.4%). Kaplan–Meier analysis showed that TP53 gene mutations and remaining C2 (detected at base line and remaining at the second cycle of chemotherapy) were significantly associated with poor PFS. Longitudinal monitoring of 27 patients during treatment showed that the molecular tumor burden index ([mTBI] a measure of the percentage of ctDNA in samples) was positively correlated with tumor size as evaluated by computed tomography (P < 0.05). The evaluations based on mTBI values were consistent with those based on CT scans in 87.5% of cases at the endpoint of clinical observation. Conclusions: ctDNA could be used to predict treatment outcomes and the mTBI is a potential method to assess therapeutic response in metastatic breast cancer. Clinical trial information: NCT01917279.