Copy number alterations in metastatic and early breast tumours: prognostic and acquired biomarkers of resistance to CDK4/6 inhibitors

Marie Paule Sablin, Pierre Gestraud, Sarah Flora Jonas, Constance Lamy, Magali Lacroix-Triki, Thomas Bachelot, Thomas Filleron, Ludovic Lacroix, Alicia Tran-Dien, Pascal Jézéquel, Marjorie Mauduit, Janice Barros Monteiro, Marta Jimenez, Stefan Michiels, Valery Attignon, Isabelle Soubeyran, Keltouma Driouch, Nicolas Servant, Christophe Le Tourneau, Maud KamalFabrice André, Ivan Bièche

    Résultats de recherche: Contribution à un journalArticleRevue par des pairs

    Résumé

    Background: Copy number alterations (CNA) are acquired during the evolution of cancers from their early stage to metastatic stage. This study aims at analysing the clinical value of the identified metastasis-associated CNAs both in metastatic breast cancers (mBCs) and early breast cancers (eBCs). Methods: Single-nucleotide polymorphism (SNP)-array was performed on 926 biopsies from mBC patients, enrolled in SAFIR02-BREAST prospective trial. CNA profiles of eBCs from The Cancer Genome Atlas Breast Invasive Carcinoma (n = 770), Molecular Taxonomy of Breast Cancer International Consortium (n = 1620) and PACS04 trial (n = 243) cohorts were used as references for comparing mBCs and eBCs CNA profiles. Overall survival was the considered survival endpoint. Results: Among the twenty-one genes frequently altered in ER + /HER2− mBCs: focal amplification of TERT was associated with poor outcome in the ER + /HER2− mBC population. Among the ER + /HER2− mBCs patients for whom CDK4/6 inhibitors information before biopsies collection was available: we identified seven genes on post-treatment biopsies, including the cyclin-dependent kinase 4 (CDK4), which was amplified in 9.8% of the ER + /HER2− mBCs pretreated population, as compared to 1.5% in the ER + /HER2− mBCs unpretreated population (P = 2.82E-04) as well as the 3 eBC populations. CDK4 amplification was associated with poor outcome in the ER + /HER2− eBCs. Conclusions: This study provides insights into the biology of mBCs and identifies clinically useful genomic features for future improvement of breast cancer patient management.

    langue originaleAnglais
    Pages (de - à)1060-1067
    Nombre de pages8
    journalBritish Journal of Cancer
    Volume131
    Numéro de publication6
    Les DOIs
    étatPublié - 5 oct. 2024

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