Timing evolution of lobular breast cancer through phylogenetic analysis Journal Article


Authors: Fimereli, D.; Venet, D.; Rediti, M.; Boeckx, B.; Maetens, M.; Majjaj, S.; Rouas, G.; Marchio, C.; Bertucci, F.; Mariani, O.; Capra, M.; Bonizzi, G.; Contaldo, F.; Galant, C.; Van den Eynden, G.; Salgado, R.; Biganzoli, E.; Vincent-Salomon, A.; Pruneri, G.; Larsimont, D.; Lambrechts, D.; Desmedt, C.; Brown, D. N.; Rothé, F.; Sotiriou, C.
Article Title: Timing evolution of lobular breast cancer through phylogenetic analysis
Abstract: 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: 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: 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: Our results provide insights into ILC evolution and offer potential paths for optimised ILC care. Funding: 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). © 2022 The Authors
Keywords: breast cancer; distant metastasis; heterogeneity; metastatic dissemination; tumour progression
Journal Title: EBioMedicine
Volume: 82
ISSN: 2352-3964
Publisher: Elsevier Inc.  
Date Published: 2022-08-01
Start Page: 104169
Language: English
DOI: 10.1016/j.ebiom.2022.104169
PROVIDER: scopus
PMCID: PMC9309404
PUBMED: 35882101
DOI/URL:
Notes: Article -- Export Date: 1 August 2022 -- Source: Scopus
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  1. David Norman Brown
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