19. Personalized ctDNA micro-panels monitor and predict clinical outcomes for patients with triple-negative breast cancer

Abstract

Circulating tumor DNA (ctDNA) in peripheral blood can predict prognosis and therapeutic response for triple-negative breast cancer (TNBC) patients. However, most approaches use large comprehensive panels of commonly mutated genes. This study assessed the use of custom micro-panels for tracking disease and predicting clinical outcomes for patients with TNBC. Paired tumor-normal samples were obtained at diagnosis and whole exome sequencing identified somatic variants. Custom micro-panels of 4-6 variants were created for each individual. Peripheral blood was obtained at baseline, during cycle1/day3, at time of surgery, and in 3-6 month intervals post-surgery. Variant allele fraction (VAF) at various time points were compared to clinical outcomes. A cohort of 50 individuals were evaluated for up to 48 months post-diagnosis. In total, 33 patients did not achieve pathological complete response (pCR) and seven patients developed clinical relapse. For all relapse patients with peripheral blood obtained <6 months prior to relapse (n = 4), the custom ctDNA micro-panels identified molecular relapse at an average of 4.3 months prior to clinical relapse. During disease monitoring, only 11% of patients with pCR had a molecular relapse, whereas 47% of patients without pCR had a molecular relapse (Chi-Square; p-value = 0.10). In conclusion, custom micro-panel can be effectively used to predict outcomes and monitor remission for patients with TNBC. These custom micro-panels show high sensitivity for detecting molecular relapse in advance of clinical relapse. The use of these panels could improve patient outcomes through early detection of relapse with preemptive intervention prior to symptom onset.