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- Title
Copy number alterations in metastatic and early breast tumours: prognostic and acquired biomarkers of resistance to CDK4/6 inhibitors.
- Authors
Sablin, Marie-Paule; Gestraud, Pierre; Jonas, Sarah Flora; Lamy, Constance; Lacroix-Triki, Magali; Bachelot, Thomas; Filleron, Thomas; Lacroix, Ludovic; Tran-Dien, Alicia; Jézéquel, Pascal; Mauduit, Marjorie; Barros Monteiro, Janice; Jimenez, Marta; Michiels, Stefan; Attignon, Valery; Soubeyran, Isabelle; Driouch, Keltouma; Servant, Nicolas; Le Tourneau, Christophe; Kamal, Maud
- Abstract
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.
- Publication
British Journal of Cancer, 2024, Vol 131, Issue 6, p1060
- ISSN
0007-0920
- Publication type
Article
- DOI
10.1038/s41416-024-02804-6