Longitudinal HER2 amplification tracked in circulating tumor DNA for therapeutic effect monitoring and prognostic evaluation in patients with breast cancer
Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved..
BACKGROUND: Human epidermal growth factor receptor 2(HER2) status is a crucial predictive factor for prognostic assessment and targeted therapy selection, which may be influenced by intratumor heterogeneity and molecular divergence between the primary site and different metastases. Therefore, we performed a prospective study to confirm the concordance of HER2 amplification in circulating tumor DNA(ctDNA) with primary tumor tissue and verified its clinical implications.
METHODS: A total of 105 breast cancer patients were enrolled, and dynamic monitoring of HER2 copy numbers in ctDNA was conducted in 31 participants during the treatment. Totally 186 plasma samples were prospectively obtained and blinded to test HER2 copy numbers in ctDNA based on low-coverage whole genome sequencing(WGS) by next-generation sequencing(NGS).
RESULTS: Comparing HER2 copy numbers in ctDNA collected before the initiation of next line of anticancer treatment with primary tumor tissue, the concordant rate of HER2 amplification was 86.5%(χ2 = 52.901, p < 0.001), with a positive and negative predictive value of 94.9% and 80.7%, respectively. Histopathologically positive, high-level amplification of HER2 copy numbers in the baseline was significantly correlated with best objective response during the anticancer therapy(p = 0.010). Moreover, HER2 copy numbers fluctuated with HER2-targeted therapeutic response, and the patients with a constantly positive level after 6 weeks of treatment appeared to suffer from significantly reduced progression free survival(p < 0.001).
CONCLUSIONS: HER2 amplification in ctDNA, with a concordance rate of over 80% with primary tumors, may be a predictive index for prognostic evaluation and therapeutic response monitoring in a noninvasive, repeatable and practical method for breast cancer patients.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2020 |
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| Erschienen: |
2020 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:49 |
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| Enthalten in: |
Breast (Edinburgh, Scotland) - 49(2020) vom: 20. Feb., Seite 261-266 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Guan, Xiuwen [VerfasserIn] |
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| Links: |
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| Themen: |
Biomarkers, Tumor |
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| Anmerkungen: |
Date Completed 23.11.2020 Date Revised 23.11.2020 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.breast.2019.12.010 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM30526026X |
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| 245 | 1 | 0 | |a Longitudinal HER2 amplification tracked in circulating tumor DNA for therapeutic effect monitoring and prognostic evaluation in patients with breast cancer |
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| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved. | ||
| 520 | |a BACKGROUND: Human epidermal growth factor receptor 2(HER2) status is a crucial predictive factor for prognostic assessment and targeted therapy selection, which may be influenced by intratumor heterogeneity and molecular divergence between the primary site and different metastases. Therefore, we performed a prospective study to confirm the concordance of HER2 amplification in circulating tumor DNA(ctDNA) with primary tumor tissue and verified its clinical implications | ||
| 520 | |a METHODS: A total of 105 breast cancer patients were enrolled, and dynamic monitoring of HER2 copy numbers in ctDNA was conducted in 31 participants during the treatment. Totally 186 plasma samples were prospectively obtained and blinded to test HER2 copy numbers in ctDNA based on low-coverage whole genome sequencing(WGS) by next-generation sequencing(NGS) | ||
| 520 | |a RESULTS: Comparing HER2 copy numbers in ctDNA collected before the initiation of next line of anticancer treatment with primary tumor tissue, the concordant rate of HER2 amplification was 86.5%(χ2 = 52.901, p < 0.001), with a positive and negative predictive value of 94.9% and 80.7%, respectively. Histopathologically positive, high-level amplification of HER2 copy numbers in the baseline was significantly correlated with best objective response during the anticancer therapy(p = 0.010). Moreover, HER2 copy numbers fluctuated with HER2-targeted therapeutic response, and the patients with a constantly positive level after 6 weeks of treatment appeared to suffer from significantly reduced progression free survival(p < 0.001) | ||
| 520 | |a CONCLUSIONS: HER2 amplification in ctDNA, with a concordance rate of over 80% with primary tumors, may be a predictive index for prognostic evaluation and therapeutic response monitoring in a noninvasive, repeatable and practical method for breast cancer patients | ||
| 650 | 4 | |a Clinical Trial | |
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Breast cancer | |
| 650 | 4 | |a HER2 amplification | |
| 650 | 4 | |a HER2 copy numbers | |
| 650 | 4 | |a ctDNA | |
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| 700 | 1 | |a Liu, Binliang |e verfasserin |4 aut | |
| 700 | 1 | |a Niu, Yunyun |e verfasserin |4 aut | |
| 700 | 1 | |a Dong, Xin |e verfasserin |4 aut | |
| 700 | 1 | |a Zhu, Xia |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Chunxiao |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Lixi |e verfasserin |4 aut | |
| 700 | 1 | |a Yi, Zongbi |e verfasserin |4 aut | |
| 700 | 1 | |a Sun, Xiaoying |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Hongyan |e verfasserin |4 aut | |
| 700 | 1 | |a Lu, Sijia |e verfasserin |4 aut | |
| 700 | 1 | |a Ma, Fei |e verfasserin |4 aut | |
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