Phylogenetic reconstruction of breast cancer reveals two routes of metastatic dissemination associated with distinct clinical outcome
Copyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved..
BACKGROUND: In breast cancer (BC), axillary lymph node (ALN) involvement is one of the strongest adverse prognostic factors. However, it is unclear whether loco-regional lymph node deposits are effectively the root of secondary metastases or only an indicator of competence of the primary tumour to spread to distant organs.
METHODS: Here, we investigated the evolutionary trajectories of primary tumour, ALN and distant metastasis samples from 16 estrogen-receptor (ER)-positive lymph node-positive BC patients. Low-pass whole genome sequencing was performed to infer somatic copy number aberrations and the phylogenetic profiles for all patients were obtained.
FINDINGS: We show that lymph nodes and distant metastases shared a common origin in only 25% of the cases highlighting that the predominant route of metastatic dissemination is the direct seeding of tumour cells from the primary tumour to distant organs, independently of lymph node metastasis. Noticeably, patients sharing a common origin significantly have worse prognosis.
INTERPRETATION: Our results shed light on the routes on which tumour cells metastasize and their role in disease progression in ER-positive BC.
FUNDING: This work has received financial support from Les Amis de l'Institut Bordet, MEDIC, the Breast Cancer Research Foundation (BCRF), the Belgian Fonds National de la Recherche Scientifique (F.R.S-FNRS) and from a grant of the Région Wallonne.
| Errataetall: |
CommentIn: EBioMedicine. 2020 Jul;57:102852. - PMID 32574957 |
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| Medienart: |
E-Artikel |
| Erscheinungsjahr: |
2020 |
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| Erschienen: |
2020 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:56 |
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| Enthalten in: |
EBioMedicine - 56(2020) vom: 25. Juni, Seite 102793 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Venet, David [VerfasserIn] |
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| Links: |
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| Themen: |
Axillary lymph node |
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| Anmerkungen: |
Date Completed 12.04.2021 Date Revised 25.05.2021 published: Print-Electronic CommentIn: EBioMedicine. 2020 Jul;57:102852. - PMID 32574957 Citation Status MEDLINE |
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| doi: |
10.1016/j.ebiom.2020.102793 |
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| PPN (Katalog-ID): |
NLM310919754 |
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| 100 | 1 | |a Venet, David |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Phylogenetic reconstruction of breast cancer reveals two routes of metastatic dissemination associated with distinct clinical outcome |
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| 500 | |a published: Print-Electronic | ||
| 500 | |a CommentIn: EBioMedicine. 2020 Jul;57:102852. - PMID 32574957 | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved. | ||
| 520 | |a BACKGROUND: In breast cancer (BC), axillary lymph node (ALN) involvement is one of the strongest adverse prognostic factors. However, it is unclear whether loco-regional lymph node deposits are effectively the root of secondary metastases or only an indicator of competence of the primary tumour to spread to distant organs | ||
| 520 | |a METHODS: Here, we investigated the evolutionary trajectories of primary tumour, ALN and distant metastasis samples from 16 estrogen-receptor (ER)-positive lymph node-positive BC patients. Low-pass whole genome sequencing was performed to infer somatic copy number aberrations and the phylogenetic profiles for all patients were obtained | ||
| 520 | |a FINDINGS: We show that lymph nodes and distant metastases shared a common origin in only 25% of the cases highlighting that the predominant route of metastatic dissemination is the direct seeding of tumour cells from the primary tumour to distant organs, independently of lymph node metastasis. Noticeably, patients sharing a common origin significantly have worse prognosis | ||
| 520 | |a INTERPRETATION: Our results shed light on the routes on which tumour cells metastasize and their role in disease progression in ER-positive BC | ||
| 520 | |a FUNDING: This work has received financial support from Les Amis de l'Institut Bordet, MEDIC, the Breast Cancer Research Foundation (BCRF), the Belgian Fonds National de la Recherche Scientifique (F.R.S-FNRS) and from a grant of the Région Wallonne | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Axillary lymph node | |
| 650 | 4 | |a Breast cancer | |
| 650 | 4 | |a Distant metastasis | |
| 650 | 4 | |a Metastatic dissemination | |
| 650 | 7 | |a Receptors, Estrogen |2 NLM | |
| 700 | 1 | |a Fimereli, Danai |e verfasserin |4 aut | |
| 700 | 1 | |a Rothé, Françoise |e verfasserin |4 aut | |
| 700 | 1 | |a Boeckx, Bram |e verfasserin |4 aut | |
| 700 | 1 | |a Maetens, Marion |e verfasserin |4 aut | |
| 700 | 1 | |a Majjaj, Samira |e verfasserin |4 aut | |
| 700 | 1 | |a Rouas, Ghizlane |e verfasserin |4 aut | |
| 700 | 1 | |a Capra, Maria |e verfasserin |4 aut | |
| 700 | 1 | |a Bonizzi, Giuseppina |e verfasserin |4 aut | |
| 700 | 1 | |a Contaldo, Federica |e verfasserin |4 aut | |
| 700 | 1 | |a Galant, Christine |e verfasserin |4 aut | |
| 700 | 1 | |a Piccart, Martine |e verfasserin |4 aut | |
| 700 | 1 | |a Pruneri, Giancarlo |e verfasserin |4 aut | |
| 700 | 1 | |a Larsimont, Denis |e verfasserin |4 aut | |
| 700 | 1 | |a Lambrechts, Diether |e verfasserin |4 aut | |
| 700 | 1 | |a Desmedt, Christine |e verfasserin |4 aut | |
| 700 | 1 | |a Sotiriou, Christos |e verfasserin |4 aut | |
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