Subtyping of metastatic breast cancer based on plasma circulating tumor DNA alterations : An observational, multicentre platform study
© 2022 The Authors..
Background: After multiple lines of therapies, no guideline or consensus is currently available for the treatment of patients with metastatic breast cancer. This study aims to evaluate the efficacy of a novel re-subtyping and treatment strategy based on ctDNA alterations.
Methods: This observational, multicentre study recruited 223 patients with metastatic breast cancer intending to receive late-line therapy from Dec 1, 2016, to June 31, 2019. This study took place in Hunan Cancer Hospital, the Forth Hospital of Changsha and Zhuzhou Central Hospital in China. ctDNA alterations were assessed by next-generation sequencing (NGS). Patients with druggable ctDNA alterations were treated with corresponding targeted drugs which are clinically available. Other patients received physician-chosen treatment. This study was registered with ClinicalTrials.gov, NCT05079074.
Findings: The progression-free survival (hazard ratio: 0.45, 95% Confidence Interval (CI): 0.33-0.62, P < 0.0001) and disease control rate (89.4% vs. 65.9%, P < 0.0001) were significantly improved in patients who received druggable ctDNA alteration-guided therapy compared with those of patients who received physician-chosen treatment. ctDNA alterations with top rank and high clustering scores were classified into four subtypes based on their functions as follows: 1) extracellular function (ECF), 2) cell proliferation (CP), 3) nuclear function (NF), and 4) cascade signaling pathway (CSP). A significant benefit from ctDNA alteration-guided treatment was observed in patients with NF and CSP ctDNA alterations, with hazard ratios of 0.39 (95% CI: 0.24-0.65, P = 0.0003) and 0.14 (95% CI: 0.04-0.46, P < 0.0001), respectively.
Interpretation: After multiline traditional pathological HR/HER2 subtype-guided therapies, ctDNA testing could identify druggable ctDNA alterations to guide late-line therapy for patients with metastatic breast cancer.
Funding: This work was supported by Key Grants of Research and Development in Hunan Province (2018SK2124, 2018SK2120), Natural Science Foundation of Hunan (2019JJ50360), Hunan Provincial Health Commission Project (B2019085, B2019089 and C2019070), and Changsha Science and Technology Project (kq2004125 and kq2004137).
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2022 |
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| Erschienen: |
2022 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:51 |
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| Enthalten in: |
EClinicalMedicine - 51(2022) vom: 15. Sept., Seite 101567 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Hu, Zhe-Yu [VerfasserIn] |
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| Links: |
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| Themen: |
Disease control rate (DCR) |
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| Anmerkungen: |
Date Revised 26.07.2022 published: Electronic-eCollection ClinicalTrials.gov: NCT05079074 Citation Status PubMed-not-MEDLINE |
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| doi: |
10.1016/j.eclinm.2022.101567 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM343957205 |
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| 100 | 1 | |a Hu, Zhe-Yu |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Subtyping of metastatic breast cancer based on plasma circulating tumor DNA alterations |b An observational, multicentre platform study |
| 264 | 1 | |c 2022 | |
| 336 | |a Text |b txt |2 rdacontent | ||
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| 500 | |a Date Revised 26.07.2022 | ||
| 500 | |a published: Electronic-eCollection | ||
| 500 | |a ClinicalTrials.gov: NCT05079074 | ||
| 500 | |a Citation Status PubMed-not-MEDLINE | ||
| 520 | |a © 2022 The Authors. | ||
| 520 | |a Background: After multiple lines of therapies, no guideline or consensus is currently available for the treatment of patients with metastatic breast cancer. This study aims to evaluate the efficacy of a novel re-subtyping and treatment strategy based on ctDNA alterations | ||
| 520 | |a Methods: This observational, multicentre study recruited 223 patients with metastatic breast cancer intending to receive late-line therapy from Dec 1, 2016, to June 31, 2019. This study took place in Hunan Cancer Hospital, the Forth Hospital of Changsha and Zhuzhou Central Hospital in China. ctDNA alterations were assessed by next-generation sequencing (NGS). Patients with druggable ctDNA alterations were treated with corresponding targeted drugs which are clinically available. Other patients received physician-chosen treatment. This study was registered with ClinicalTrials.gov, NCT05079074 | ||
| 520 | |a Findings: The progression-free survival (hazard ratio: 0.45, 95% Confidence Interval (CI): 0.33-0.62, P < 0.0001) and disease control rate (89.4% vs. 65.9%, P < 0.0001) were significantly improved in patients who received druggable ctDNA alteration-guided therapy compared with those of patients who received physician-chosen treatment. ctDNA alterations with top rank and high clustering scores were classified into four subtypes based on their functions as follows: 1) extracellular function (ECF), 2) cell proliferation (CP), 3) nuclear function (NF), and 4) cascade signaling pathway (CSP). A significant benefit from ctDNA alteration-guided treatment was observed in patients with NF and CSP ctDNA alterations, with hazard ratios of 0.39 (95% CI: 0.24-0.65, P = 0.0003) and 0.14 (95% CI: 0.04-0.46, P < 0.0001), respectively | ||
| 520 | |a Interpretation: After multiline traditional pathological HR/HER2 subtype-guided therapies, ctDNA testing could identify druggable ctDNA alterations to guide late-line therapy for patients with metastatic breast cancer | ||
| 520 | |a Funding: This work was supported by Key Grants of Research and Development in Hunan Province (2018SK2124, 2018SK2120), Natural Science Foundation of Hunan (2019JJ50360), Hunan Provincial Health Commission Project (B2019085, B2019089 and C2019070), and Changsha Science and Technology Project (kq2004125 and kq2004137) | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Disease control rate (DCR) | |
| 650 | 4 | |a Druggable circulating tumor DNA alterations | |
| 650 | 4 | |a Genetic alterations of functional pathways | |
| 650 | 4 | |a Late-line therapy | |
| 650 | 4 | |a Progression-free survival (PFS) | |
| 700 | 1 | |a Tang, Yu |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Liping |e verfasserin |4 aut | |
| 700 | 1 | |a Xie, Ning |e verfasserin |4 aut | |
| 700 | 1 | |a Tian, Can |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Binliang |e verfasserin |4 aut | |
| 700 | 1 | |a Zou, Lixin |e verfasserin |4 aut | |
| 700 | 1 | |a Zhou, Wei |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Yikai |e verfasserin |4 aut | |
| 700 | 1 | |a Xia, Xuefeng |e verfasserin |4 aut | |
| 700 | 1 | |a Ouyang, Quchang |e verfasserin |4 aut | |
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