Giannoudis A, Sokol E S, Bhogal T, Ramkissoon S H, Razis E D, Bartsch R, Shaw J A, McGregor K, Clark Alison, Huang R S P, Palmieri C
Institute of Systems, Molecular and Integrative Biology, Molecular and Clinical Cancer Medicine, University of Liverpool, Liverpool, UK.
Foundation Medicine, Inc., Boston, MA, USA.
NPJ Precis Oncol. 2024 Dec 20;8(1):282. doi: 10.1038/s41698-024-00761-0.
Understanding the genomic landscape of breast cancer brain metastases (BCBMs) is key to developing targeted treatments. In this study, targetable genomic profiling was performed on 822 BCBMs, 11,988 local breast cancer (BC) biopsies and 15,516 non-central nervous system (N-CNS) metastases (all unpaired samples) collected during the course of routine clinical care by Foundation Medicine Inc (Boston, MA). Clinically relevant genomic alterations were significantly enriched in BCBMs compared to local BCs and N-CNS metastases. Homologous recombination deficiency as measured by BRCA1/2 alteration prevalence and loss-of-heterozygosity and immune checkpoint inhibitor (ICI) biomarkers [Tumor mutation burden (TMB)-High, Microsatellite instability (MSI)-High, PD-L1/L2)] were significantly more prevalent in BCBM than local BC and N-CNS. High PD-L1 protein expression was observed in ER-negative/HER2-negative BCBMs (48.3% vs 50.0% in local BCs, 21.4% in N-CNS). Our data highlights that a high proportion of BCBMs are potentially amenable to treatment with targeted therapeutic agents including PARP inhibitors and ICIs.
了解乳腺癌脑转移（BCBM）的基因组格局是开发靶向治疗方法的关键。在本研究中，对Foundation Medicine公司（马萨诸塞州波士顿）在常规临床护理过程中收集的822例BCBM、11988例局部乳腺癌（BC）活检样本和15516例非中枢神经系统（N-CNS）转移样本（均为非配对样本）进行了可靶向基因组分析。与局部BC和N-CNS转移相比，临床相关的基因组改变在BCBM中显著富集。通过BRCA1/2改变患病率、杂合性缺失和免疫检查点抑制剂（ICI）生物标志物[肿瘤突变负荷（TMB）高、微卫星不稳定性（MSI）高、PD-L1/L2]测量的同源重组缺陷在BCBM中比局部BC和N-CNS更普遍。在雌激素受体阴性/人表皮生长因子受体2阴性的BCBM中观察到高PD-L1蛋白表达（局部BC中为48.3%对50.0%，N-CNS中为21.4%）。我们的数据突出表明，很大一部分BCBM可能适合用包括聚（ADP-核糖）聚合酶（PARP）抑制剂和ICI在内的靶向治疗药物进行治疗。
