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



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 3 weeks of PORT (T1), and 1 month 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 22 months, 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.

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Availability of data and materials

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.



Neoadjuvant chemotherapy


Breast-conserving surgery


Axillary lymph node


Triple-negative breast cancer


Postoperative radiotherapy


Human epidermal growth factor receptor 2






Complete pathologic response


Minimal residual disease


Cell-free DNA


Circulating tumor DNA


Circulating tumor cells


Disseminated tumor cells


Next-generation sequencing




Magnetic resonance imaging


Computed tomography


Internal mammary lymph node


Supraclavicular lymph node


Chest wall


Peripheral blood leukocytes


Genomic DNA


Variant allele frequency


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This study was supported by grants from the Ministry of Science and ICT, Republic of Korea (NRF-2019R1F1A1062069) and Samsung Medical Center (SMO 1200821 and SMO 1200391). The funding sources had no involvement in the study design, data collection, data analysis, data interpretation, writing of this report, or the decision to submit this article for publication.

Author information




HK designed and directed the study. YJK, DP, and WYP analyzed and interpreted the mutational data. HK and YJK wrote the manuscript. DHC, WP, WKC, and NK aided in interpreting the results. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Haeyoung Kim.

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The authors declare that they have no competing interests.

Ethics approval and consent to participate

All patients provided consents to participate. This study was approved by the institutional review board of the Samsung Medical Center (approval number, SMC 2018-10-137-009).

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This study was presented as a poster at the 17th St. Gallen International Breast Cancer Conference on March 17, 2021.

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Kim, H., Kim, Y.J., Park, D. et al. Dynamics of circulating tumor DNA during postoperative radiotherapy in patients with residual triple-negative breast cancer following neoadjuvant chemotherapy: a prospective observational study. Breast Cancer Res Treat 189, 167–175 (2021). https://doi.org/10.1007/s10549-021-06296-3

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  • Circulating tumor DNA
  • Breast neoplasms
  • Triple Negative Breast Neoplasms
  • Radiotherapy