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.
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BibTeX
@article{fimereli2026timing,
title = {{Timing evolution of lobular breast cancer through phylogenetic analysis}},
author = {Danai Fimereli and David Venet and Mattia Rediti and Bram Boeckx and Marion Maetens and Samira Majjaj and Ghizlane Rouas and Caterina Marchio and François Bertucci and Odette Mariani and Maria Capra and Giuseppina Bonizzi and Federica Contaldo and Christine Galant and Gert van Den Eynden and Roberto Salgado and Elia Biganzoli and Anne Vincent-Salomon and Giancarlo Pruneri and Denis Larsimont and Diether Lambrechts and Christine Desmedt and David N. Brown and Francoise Rothe and Christos Sotiriou},
journal = {EBioMedicine},
year = {2026},
month = nov,
doi = {10.1016/j.ebiom.2022.104169},
url = {https://amu.hal.science/hal-04084988v1},
note = {CC BY-NC-ND 4.0},
}
RIS
TY - JOUR
TI - Timing evolution of lobular breast cancer through phylogenetic analysis
AU - Danai Fimereli
AU - David Venet
AU - Mattia Rediti
AU - Bram Boeckx
AU - Marion Maetens
AU - Samira Majjaj
AU - Ghizlane Rouas
AU - Caterina Marchio
AU - François Bertucci
AU - Odette Mariani
AU - Maria Capra
AU - Giuseppina Bonizzi
AU - Federica Contaldo
AU - Christine Galant
AU - Gert van Den Eynden
AU - Roberto Salgado
AU - Elia Biganzoli
AU - Anne Vincent-Salomon
AU - Giancarlo Pruneri
AU - Denis Larsimont
AU - Diether Lambrechts
AU - Christine Desmedt
AU - David N. Brown
AU - Francoise Rothe
AU - Christos Sotiriou
PY - 2026
DA - 2026/11/03
JO - EBioMedicine
DO - 10.1016/j.ebiom.2022.104169
UR - https://amu.hal.science/hal-04084988v1
AB - 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.
SN - 2352-3964
ER -