Liquid biopsy prediction of axillary lymph node metastasis, cancer recurrence, and patient survival in breast cancer: A meta-analysis

Ju-Han Lee, Hoiseon Jeong, Jung-Woo Choi, Hwa Eun Oh, Young Sik Kim

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

BACKGROUND: Liquid biopsies using circulating tumor DNA (ctDNA) and cell-free DNA (cfDNA) have been developed for early cancer detection and patient monitoring. To investigate the clinical usefulness of ctDNA aberrations and cfDNA levels in patients with breast cancer (BC), we conducted a meta-analysis of 69 published studies on 5736 patients with BC. METHODS: The relevant publications were identified by searching PubMed and Embase databases. The effect sizes of outcome parameters were pooled using a random-effects model. RESULTS: The ctDNA mutation rates of TP53, PIK3CA, and ESR1 were approximately 38%, 27%, and 32%, respectively. High levels of cfDNA were associated with BCs rather than with healthy controls. However, these detection rates were not satisfactory for BC screening. Although the precise mechanisms have been unknown, high cfDNA levels were significantly associated with axillary lymph node metastasis (odds ratio [OR] = 2.148, P = .030). The ctDNA mutations were significantly associated with cancer recurrence (OR = 3.793, P < .001), short disease-free survival (univariate hazard ratio [HR] = 5.180, P = .026; multivariate HR = 3.605, P = .001), and progression-free survival (HR = 1.311, P = .013) rates, and poor overall survival outcomes (HR = 2.425, P = .007). CONCLUSION: This meta-analysis demonstrates that ctDNA mutation status predicts disease recurrence and unfavorable survival outcomes, while cfDNA levels can be predictive of axillary lymph node metastasis in patients with BC.

Original languageEnglish
Pages (from-to)e12862
JournalMedicine
Volume97
Issue number42
DOIs
Publication statusPublished - 2018 Oct 1

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Meta-Analysis
Lymph Nodes
Breast Neoplasms
Neoplasm Metastasis
Biopsy
Recurrence
Survival
DNA
Neoplasms
Early Detection of Cancer
Disease-Free Survival
Odds Ratio
Circulating Neoplastic Cells
Mutation
Physiologic Monitoring
Mutation Rate
PubMed
Publications
Databases

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Liquid biopsy prediction of axillary lymph node metastasis, cancer recurrence, and patient survival in breast cancer : A meta-analysis. / Lee, Ju-Han; Jeong, Hoiseon; Choi, Jung-Woo; Oh, Hwa Eun; Kim, Young Sik.

In: Medicine, Vol. 97, No. 42, 01.10.2018, p. e12862.

Research output: Contribution to journalArticle

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abstract = "BACKGROUND: Liquid biopsies using circulating tumor DNA (ctDNA) and cell-free DNA (cfDNA) have been developed for early cancer detection and patient monitoring. To investigate the clinical usefulness of ctDNA aberrations and cfDNA levels in patients with breast cancer (BC), we conducted a meta-analysis of 69 published studies on 5736 patients with BC. METHODS: The relevant publications were identified by searching PubMed and Embase databases. The effect sizes of outcome parameters were pooled using a random-effects model. RESULTS: The ctDNA mutation rates of TP53, PIK3CA, and ESR1 were approximately 38{\%}, 27{\%}, and 32{\%}, respectively. High levels of cfDNA were associated with BCs rather than with healthy controls. However, these detection rates were not satisfactory for BC screening. Although the precise mechanisms have been unknown, high cfDNA levels were significantly associated with axillary lymph node metastasis (odds ratio [OR] = 2.148, P = .030). The ctDNA mutations were significantly associated with cancer recurrence (OR = 3.793, P < .001), short disease-free survival (univariate hazard ratio [HR] = 5.180, P = .026; multivariate HR = 3.605, P = .001), and progression-free survival (HR = 1.311, P = .013) rates, and poor overall survival outcomes (HR = 2.425, P = .007). CONCLUSION: This meta-analysis demonstrates that ctDNA mutation status predicts disease recurrence and unfavorable survival outcomes, while cfDNA levels can be predictive of axillary lymph node metastasis in patients with BC.",
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N2 - BACKGROUND: Liquid biopsies using circulating tumor DNA (ctDNA) and cell-free DNA (cfDNA) have been developed for early cancer detection and patient monitoring. To investigate the clinical usefulness of ctDNA aberrations and cfDNA levels in patients with breast cancer (BC), we conducted a meta-analysis of 69 published studies on 5736 patients with BC. METHODS: The relevant publications were identified by searching PubMed and Embase databases. The effect sizes of outcome parameters were pooled using a random-effects model. RESULTS: The ctDNA mutation rates of TP53, PIK3CA, and ESR1 were approximately 38%, 27%, and 32%, respectively. High levels of cfDNA were associated with BCs rather than with healthy controls. However, these detection rates were not satisfactory for BC screening. Although the precise mechanisms have been unknown, high cfDNA levels were significantly associated with axillary lymph node metastasis (odds ratio [OR] = 2.148, P = .030). The ctDNA mutations were significantly associated with cancer recurrence (OR = 3.793, P < .001), short disease-free survival (univariate hazard ratio [HR] = 5.180, P = .026; multivariate HR = 3.605, P = .001), and progression-free survival (HR = 1.311, P = .013) rates, and poor overall survival outcomes (HR = 2.425, P = .007). CONCLUSION: This meta-analysis demonstrates that ctDNA mutation status predicts disease recurrence and unfavorable survival outcomes, while cfDNA levels can be predictive of axillary lymph node metastasis in patients with BC.

AB - BACKGROUND: Liquid biopsies using circulating tumor DNA (ctDNA) and cell-free DNA (cfDNA) have been developed for early cancer detection and patient monitoring. To investigate the clinical usefulness of ctDNA aberrations and cfDNA levels in patients with breast cancer (BC), we conducted a meta-analysis of 69 published studies on 5736 patients with BC. METHODS: The relevant publications were identified by searching PubMed and Embase databases. The effect sizes of outcome parameters were pooled using a random-effects model. RESULTS: The ctDNA mutation rates of TP53, PIK3CA, and ESR1 were approximately 38%, 27%, and 32%, respectively. High levels of cfDNA were associated with BCs rather than with healthy controls. However, these detection rates were not satisfactory for BC screening. Although the precise mechanisms have been unknown, high cfDNA levels were significantly associated with axillary lymph node metastasis (odds ratio [OR] = 2.148, P = .030). The ctDNA mutations were significantly associated with cancer recurrence (OR = 3.793, P < .001), short disease-free survival (univariate hazard ratio [HR] = 5.180, P = .026; multivariate HR = 3.605, P = .001), and progression-free survival (HR = 1.311, P = .013) rates, and poor overall survival outcomes (HR = 2.425, P = .007). CONCLUSION: This meta-analysis demonstrates that ctDNA mutation status predicts disease recurrence and unfavorable survival outcomes, while cfDNA levels can be predictive of axillary lymph node metastasis in patients with BC.

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