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

Overview

Journal Elife

Specialty Biology

Date 2023 Nov 6

PMID 37929934

Authors

Yajing Chi

Mu Su

Dongdong Zhou

Fangchao Zheng

Baoxuan Zhang

Ling Qiang

Guohua Ren

Lihua Song

Bing Bu

Shu Fang

Bo Yu

Jinxing Zhou

Jinming Yu

Huihui Li

Affiliations

Soon will be listed here.

Abstract

Background: Limited data are available on applying 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 months . 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 months .11.27 months, p=0.007) and patients with a lower ctDNA% (5.45 months . 12.17 months, p<0.001), respectively. Positive correlations with treatment response were observed for MATH score (=0.24, p=0.014) and ctDNA% (=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 months . 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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