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Abstract
Background: 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).

Methods: 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 3 weeks of PORT (T1), and 1 month after PORT (T2). Serial changes in ctDNA variant allele frequency (VAF) were analyzed.

Results: 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 22 months, no patient showed cancer recurrence.

Conclusion: 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.

Affiliations

Haeyoung Kim #  1 , Yeon Jeong Kim #  2 , Donghyun Park  2   3 , Woong-Yang Park  2   4 , Doo Ho Choi  5 , Won Park  5 , Won Kyung Cho  5 , Nalee Kim  5
1 Department of Radiation Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-Ro, Gangnam-gu, Seoul, 06351, Republic of Korea. haeyoung0131.kim@samsung.com.
2 Samsung Genome Institute, Samsung Medical Center, Seoul, South Korea.
3 GENINUS Inc, Seoul, South Korea.
4 Department of Molecular Cell Biology, Sungkyunkwan University School of Medicine, Suwon, South Korea.
5 Department of Radiation Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-Ro, Gangnam-gu, Seoul, 06351, Republic of Korea.
# Contributed equally.