Giannoudis, A 
ORCID: 0000-0002-7200-1497, Sokol, ES, Bhogal, T ORCID: 0000-0003-3297-9957, Ramkissoon, SH, Razis, ED ORCID: 0000-0003-3873-2947, Bartsch, R, Shaw, JA, McGregor, K, Clark, Alison, Huang, RSP ORCID: 0000-0001-8395-5168 et al (show 1 more authors)
(2024)
Breast cancer brain metastases genomic profiling identifies alterations targetable by immune-checkpoint and PARP inhibitors.
NPJ precision oncology, 8 (1).
282-.
ISSN 2397-768X, 2397-768X
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PDF
Breast cancer brain metastases genomic profiling identifies alterations targetable by immune-checkpoint and PARP inhibitors.pdf - Open Access published version Available under License Creative Commons Attribution. Download (1MB) | Preview |
Abstract
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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | 32 Biomedical and Clinical Sciences, 3211 Oncology and Carcinogenesis, 3204 Immunology, Breast Cancer, Human Genome, Cancer Genomics, Immunotherapy, Cancer, Rare Diseases, Precision Medicine, Genetics, Women's Health, Neurosciences, Biotechnology, 5.1 Pharmaceuticals, Cancer, 3 Good Health and Well Being |
| Divisions: | Faculty of Health and Life Sciences Faculty of Health and Life Sciences > Institute of Life Courses and Medical Sciences Faculty of Health and Life Sciences > Institute of Life Courses and Medical Sciences > School of Dentistry Faculty of Health and Life Sciences > Institute of Systems, Molecular and Integrative Biology |
| Depositing User: | Symplectic Admin |
| Date Deposited: | 31 Jan 2025 15:52 |
| Last Modified: | 28 Aug 2025 05:35 |
| DOI: | 10.1038/s41698-024-00761-0 |
| Related Websites: | |
| URI: | https://livrepository.liverpool.ac.uk/id/eprint/3190045 |
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