Timing evolution of lobular breast cancer through phylogenetic analysis.
Breast cancer
Distant metastasis
Heterogeneity
Metastatic dissemination
Tumour progression
Journal
EBioMedicine
ISSN: 2352-3964
Titre abrégé: EBioMedicine
Pays: Netherlands
ID NLM: 101647039
Informations de publication
Date de publication:
Aug 2022
Aug 2022
Historique:
received:
31
01
2022
revised:
22
06
2022
accepted:
30
06
2022
pubmed:
27
7
2022
medline:
17
8
2022
entrez:
26
7
2022
Statut:
ppublish
Résumé
Late distant recurrence is a challenge for the treatment of invasive lobular carcinoma (ILC) of the breast. Despite in-depth characterisation of primary ILC, the molecular landscape of metastatic ILC is still only partially understood. We retrospectively identified 38 ILC patients from the tissue banks of six European institutions. DNA extracted from patient matched primary and metastatic FFPE tissue blocks was whole genome sequenced to compute somatic copy number aberrations. This, in turn, was used to infer the evolutionary history of these patients. The data show different metastatic seeding patterns, with both an early and late divergence of the metastatic lineage observed in ILC. Additionally, cascading dissemination from a metastatic precursor was a dominant rule. Alterations in key cancer driver genes, such as TP53 or CCND1, were acquired early while additional aberrations were present only in the metastatic branch. In about 30% of the patients, the metastatic lineage harboured less aberrations than the primary tumour suggesting a period of tumour dormancy or prolonged adaptation at the distant site. This phenomenon was mostly observed in tumours from de novo metastatic patients. Our results provide insights into ILC evolution and offer potential paths for optimised ILC care. This work has received financial support from Les Amis de l'Institut Bordet, MEDIC, the Breast Cancer Research Foundation (BCRF) and the Belgian Fonds National de la Recherche Scientifique (F.R.S-FNRS).
Sections du résumé
BACKGROUND
BACKGROUND
Late distant recurrence is a challenge for the treatment of invasive lobular carcinoma (ILC) of the breast. Despite in-depth characterisation of primary ILC, the molecular landscape of metastatic ILC is still only partially understood.
METHODS
METHODS
We retrospectively identified 38 ILC patients from the tissue banks of six European institutions. DNA extracted from patient matched primary and metastatic FFPE tissue blocks was whole genome sequenced to compute somatic copy number aberrations. This, in turn, was used to infer the evolutionary history of these patients.
FINDINGS
RESULTS
The data show different metastatic seeding patterns, with both an early and late divergence of the metastatic lineage observed in ILC. Additionally, cascading dissemination from a metastatic precursor was a dominant rule. Alterations in key cancer driver genes, such as TP53 or CCND1, were acquired early while additional aberrations were present only in the metastatic branch. In about 30% of the patients, the metastatic lineage harboured less aberrations than the primary tumour suggesting a period of tumour dormancy or prolonged adaptation at the distant site. This phenomenon was mostly observed in tumours from de novo metastatic patients.
INTERPRETATION
CONCLUSIONS
Our results provide insights into ILC evolution and offer potential paths for optimised ILC care.
FUNDING
BACKGROUND
This work has received financial support from Les Amis de l'Institut Bordet, MEDIC, the Breast Cancer Research Foundation (BCRF) and the Belgian Fonds National de la Recherche Scientifique (F.R.S-FNRS).
Identifiants
pubmed: 35882101
pii: S2352-3964(22)00350-4
doi: 10.1016/j.ebiom.2022.104169
pmc: PMC9309404
pii:
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
104169Subventions
Organisme : NCI NIH HHS
ID : P30 CA008748
Pays : United States
Informations de copyright
Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of interests C.S.: advisory board (receipt of honoraria or consultations fees): Astellas, Cepheid, Vertex, Seattle genetics, Puma, Amgen. Participation in company sponsored speaker's bureau: Eisai, Prime Oncology, Teva, Foundation Medicine. Other support (travel, accommodation expenses): Roche, Genentech, Pfizer (outside the submitted work). C.M. has received personal consultancy fees from Bayer, Roche, AstraZeneca, Daiichi Sankyo outside the scope of the submitted work; Grants from Italian Association for Cancer Research (AIRC); honoraria for lectures, presentations from Novartis. R.S. reports funding for research not related to the current manuscript from Breast Cancer Research Foundation; honoraria for lectures unrelated to the current manuscript from Bristol Myers Squibb; congress registration and travel not related to the current manuscript from Merck and Bristol Myers Squibb; participation on advisory boards unrelated to the current manuscript from Roche and Bristol Myers Squibb. R.S. has no conflicts of interests related to this project. G.E. reports consulting fees as general medical affairs consultancy from Thermofisher; role as secretary on the board of the scientific working group of the Belgian Society of Pathology and board member of the Belgian Society of Pathology not reimbursed. All other authors have no conflicts of interest.