Phylogenetic reconstruction of breast cancer reveals two routes of metastatic dissemination associated with distinct clinical outcome.
Aged, 80 and over
Axilla
Breast Neoplasms
/ genetics
Evolution, Molecular
Female
High-Throughput Nucleotide Sequencing
Humans
Lymphatic Metastasis
/ genetics
Middle Aged
Neoplasm Metastasis
/ genetics
Neoplasm Seeding
Phylogeny
Prognosis
Receptors, Estrogen
/ metabolism
Whole Genome Sequencing
/ methods
Axillary lymph node
Breast cancer
Distant metastasis
Metastatic dissemination
Journal
EBioMedicine
ISSN: 2352-3964
Titre abrégé: EBioMedicine
Pays: Netherlands
ID NLM: 101647039
Informations de publication
Date de publication:
Jun 2020
Jun 2020
Historique:
received:
16
12
2019
revised:
24
04
2020
accepted:
27
04
2020
pubmed:
9
6
2020
medline:
13
4
2021
entrez:
9
6
2020
Statut:
ppublish
Résumé
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. 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. 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. Our results shed light on the routes on which tumour cells metastasize and their role in disease progression in ER-positive BC. 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.
Sections du résumé
BACKGROUND
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
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
RESULTS
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
CONCLUSIONS
Our results shed light on the routes on which tumour cells metastasize and their role in disease progression in ER-positive BC.
FUNDING
BACKGROUND
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.
Identifiants
pubmed: 32512508
pii: S2352-3964(20)30168-7
doi: 10.1016/j.ebiom.2020.102793
pmc: PMC7281848
pii:
doi:
Substances chimiques
Receptors, Estrogen
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
102793Commentaires et corrections
Type : CommentIn
Informations de copyright
Copyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of Competing Interest The authors declare no competing interests.
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