Copy number alterations in metastatic and early breast tumours: prognostic and acquired biomarkers of resistance to CDK4/6 inhibitors
Menée à l'aide de données portant sur 2 633 patientes atteintes d'un cancer du sein triple négatif ou ER+/HER2- de stade précoce et menée à partir de l'analyse de 926 échantillons biopsiques prélevés sur des patientes atteintes d'un cancer métastatique du sein triple négatif ou ER+/HER2-, cette étude identifie des amplifications géniques associées au pronostic
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.
British Journal of Cancer , article en libre accès, 2024