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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

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 enro...

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Autores principales: Chi, Yajing, Su, Mu, Zhou, Dongdong, Zheng, Fangchao, Zhang, Baoxuan, Qiang, Ling, Ren, Guohua, Song, Lihua, Bu, Bing, Fang, Shu, Yu, Bo, Zhou, Jinxing, Yu, Jinming, Li, Huihui
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10627511/
https://www.ncbi.nlm.nih.gov/pubmed/37929934
http://dx.doi.org/10.7554/eLife.90198
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author Chi, Yajing
Su, Mu
Zhou, Dongdong
Zheng, Fangchao
Zhang, Baoxuan
Qiang, Ling
Ren, Guohua
Song, Lihua
Bu, Bing
Fang, Shu
Yu, Bo
Zhou, Jinxing
Yu, Jinming
Li, Huihui
author_facet Chi, Yajing
Su, Mu
Zhou, Dongdong
Zheng, Fangchao
Zhang, Baoxuan
Qiang, Ling
Ren, Guohua
Song, Lihua
Bu, Bing
Fang, Shu
Yu, Bo
Zhou, Jinxing
Yu, Jinming
Li, Huihui
author_sort Chi, Yajing
collection PubMed
description 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 vs. 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 vs.11.27 months, p=0.007) and patients with a lower ctDNA% (5.45 months vs. 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 months vs. 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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spelling pubmed-106275112023-11-07 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 Chi, Yajing Su, Mu Zhou, Dongdong Zheng, Fangchao Zhang, Baoxuan Qiang, Ling Ren, Guohua Song, Lihua Bu, Bing Fang, Shu Yu, Bo Zhou, Jinxing Yu, Jinming Li, Huihui eLife Medicine 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 vs. 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 vs.11.27 months, p=0.007) and patients with a lower ctDNA% (5.45 months vs. 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 months vs. 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). eLife Sciences Publications, Ltd 2023-11-06 /pmc/articles/PMC10627511/ /pubmed/37929934 http://dx.doi.org/10.7554/eLife.90198 Text en © 2023, Chi et al https://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Medicine
Chi, Yajing
Su, Mu
Zhou, Dongdong
Zheng, Fangchao
Zhang, Baoxuan
Qiang, Ling
Ren, Guohua
Song, Lihua
Bu, Bing
Fang, Shu
Yu, Bo
Zhou, Jinxing
Yu, Jinming
Li, Huihui
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
title 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
title_full 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
title_fullStr 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
title_full_unstemmed 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
title_short 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
title_sort 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
topic Medicine
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10627511/
https://www.ncbi.nlm.nih.gov/pubmed/37929934
http://dx.doi.org/10.7554/eLife.90198
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