Dynamics of circulating tumor DNA during postoperative radiotherapy in patients with residual triple-negative breast cancer following neoadjuvant chemotherapy: a prospective observational study.

Abstract

This study was performed to evaluate circulating tumor DNA (ctDNA) kinetics during postoperative radiotherapy (PORT) in patients with residual triple-negative breast cancer (TNBC) at surgery following neoadjuvant chemotherapy (NAC). Stage II/III patients with post-NAC residual TNBC who required PORT were prospectively included in this study between March 2019 and July 2020. For 11 TNBC patients, next-generation sequencing targeting 38 genes was conducted in 55 samples, including tumor tissue, three plasma samples, and leukocytes from each patient. The plasma samples were collected at three-time points; pre-PORT (T0), after 3weeks of PORT (T1), and 1month after PORT (T2). Serial changes in ctDNA variant allele frequency (VAF) were analyzed. Somatic variants were found in the tumor specimens in 9 out of 11 (81.8%) patients. Mutated genes included TP53 (n = 7); PIK3CA (n = 2); and AKT1, APC, CSMD3, MYC, PTEN, and RB1 (n = 1). These tumor mutations were not found in plasma samples. Plasma ctDNA variants were detected in three (27.3%) patients at T0. Mutations in EGFR (n = 1), CTNNB1 (n = 1), and MAP2K (n = 1) was identified with ctDNA analysis. In two (18.2%) patients, the ctDNA VAF decreased through T1 and T2 while increasing at T2 in one (9.1%) patient. After a median follow-up of 22months, no patient showed cancer recurrence. Among patients with post-NAC residual TNBC, more than a quarter exhibited a detectable amount of ctDNA after curative surgery. The ctDNA VAF changed variably during the course of PORT. Therefore, ctDNA kinetics can serve as a biomarker for optimizing adjuvant treatment.