转移性和早期乳腺肿瘤的拷贝数变化：CDK4/6 抑制剂耐药性的预后和获得性生物标志物。
Copy number alterations in metastatic and early breast tumours: prognostic and acquired biomarkers of resistance to CDK4/6 inhibitors.
发表日期：2024 Aug 02
作者：
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 Kamal, Fabrice André, Ivan Bièche
来源：
BRITISH JOURNAL OF CANCER
摘要：
拷贝数改变（CNA）是在癌症从早期阶段到转移阶段的演变过程中获得的。本研究旨在分析已确定的转移相关 CNA 在转移性乳腺癌 (mBC) 和早期乳腺癌 (eBC) 中的临床价值。对 926 名 mBC 患者的活检进行了单核苷酸多态性 (SNP) 阵列分析SAFIR02-BREAST 前瞻性试验中。来自癌症基因组图谱乳腺癌浸润性癌 (n = 770)、乳腺癌国际联盟分子分类学 (n = 1620) 和 PACS04 试验 (n = 243) 队列的 eBC CNA 图谱用作比较 mBC 和 eBC CNA 图谱的参考。总生存期是所考虑的生存终点。在 ER /HER2- mBC 中经常改变的 21 个基因中：TERT 的局部扩增与 ER /HER2- mBC 群体的不良预后相关。在活检收集前可获得 CDK4/6 抑制剂信息的 ER /HER2- mBC 患者中：我们在治疗后活检中发现了 7 个基因，包括细胞周期蛋白依赖性激酶 4 (CDK4)，该基因在 9.8% 的患者中扩增。 ER /HER2- mBCs 预处理群体，相比之下，ER /HER2- mBCs 未预处理群体为 1.5% (P = 2.82E-04) 以及 3 个 eBC 群体。 CDK4 扩增与 ER /HER2- eBC 的不良结果相关。这项研究提供了对 mBC 生物学的见解，并确定了临床上有用的基因组特征，以促进未来改善乳腺癌患者管理。© 2024。作者。
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).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.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.This study provides insights into the biology of mBCs and identifies clinically useful genomic features for future improvement of breast cancer patient management.© 2024. The Author(s).