Dynamic Analysis of Circulating Tumor DNA to Predict the Prognosis and Monitor the Treatment Response of Patients with Metastatic Triple-negative Breast Cancer: a prospective study

  1. Yajing Chi
  2. Mu Su
  3. Dongdong Zhou
  4. Fangchao Zheng
  5. Baoxuan Zhang
  6. Ling Qiang
  7. Guohua Ren
  8. Lihua Song
  9. Bing Bu
  10. Shu Fang
  11. Bo Yu
  12. Jinxing Zhou
  13. Jinming Yu
  14. Huihui Li
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Abstract

Background

Limited data are available on the application of circulating tumor DNA (ctDNA) in metastatic triple-negative breast cancer (mTNBC) patients. Here, we investigated the value of ctDNA for predicting the prognosis and monitoring the treatment response in mTNBC patients.

Methods

We prospectively enrolled 70 Chinese patients with mTNBC who had progressed after ≤ 2 lines of chemotherapy and collected blood samples to extract ctDNA for 457-gene targeted panel sequencing.

Results

Patients with ctDNA+, defined by 12 prognosis-relevant mutated genes, had a shorter progression-free survival (PFS) than ctDNA− patients (5.16 monthsvs.9.05 months,P= 0.001) and ctDNA+ was independently associated with a shorter PFS (HR, 95%CI: 2.67, 1.2–5.96;P= 0.016) by multivariable analyses. Patients with a higher mutant-allele tumor heterogeneity (MATH) score (≥ 6.316) or a higher ctDNA fraction (ctDNA% ≥ 0.05) had a significantly shorter PFS than patients with a lower MATH score (5.67 monthsvs.11.27 months,P= 0.007) and patients with a lower ctDNA% (5.45 monthsvs.12.17 months,P< 0.001), respectively. Positive correlations with treatment response were observed for MATH score (R = 0.24,P= 0.014) and ctDNA% (R = 0.3,P= 0.002), but not the CEA, CA125, or CA153. Moreover, patients who remained ctDNA+ during dynamic monitoring tended to have a shorter PFS than those who did not (3.90 monthsvs.6.10 months,P= 0.135).

Conclusions

ctDNA profiling provides insight into the mutational landscape of mTNBC and may reliably predict the prognosis and treatment response of mTNBC patients.

Funding

This work was supported by the National Natural Science Foundation of China (Grant No. 81902713), Natural Science Foundation of Shandong Province (Grant No. ZR2019LZL018), Breast Disease Research Fund of Shandong Provincial Medical Association (Grant No. YXH2020ZX066), the Start-up Fund of Shandong Cancer Hospital (Grant No. 2020-PYB10), Beijing Science and Technology Innovation Fund (Grant No. KC2021-ZZ-0010-1).

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