Abstract PD4-09: Comprehensive assessment of the genomic landscape of breast cancer brain metastases reveals targetable alterations and genomic signatures relevant to immune-checkpoint and PARP inhibitors

Autor: Athina Giannoudis, Ethan Sokol, Shakti H Ramkissoon, Talvinder Bhogal, Kimberly McGregor, Allison Clark, Evangelia D Razis, Rupert Bartsch, Richard SP Huang, Carlo Palmieri
Rok vydání: 2022
Předmět:
Zdroj: Cancer Research. 82:PD4-09
ISSN: 1538-7445
0008-5472
DOI: 10.1158/1538-7445.sabcs21-pd4-09
Popis: Background: Central nervous system (CNS) disease secondary to breast cancer (BC) is a growing clinical problem and a cause of significant morbidity and mortality. A better understanding of the genomic landscape is key to understanding its cause and to developing novel treatments. In this study, we examined the genomic landscape of a large cohort of breast cancer brain metastases (BMs) and compared them to a cohort of local breast cancers (BCs) and non-CNS metastases (N-CNS). Material and Methods: We analyzed 822 BMs and compared them to 11,988 local, breast-biopsied BCs and 15,516 N-CNS (unpaired samples) with comprehensive genomic profiling (CGP) for all classes of alterations in at least 324 genes (Foundation Medicine, Cambridge, MA, USA). Homologous recombination deficiency detected by genome-wide loss of heterozygosity (HRD-gLOH; cutoff 16%), tumour mutation burden (TMB; cutoff 10 mutations/Mb), microsatellite instability (MSI) and PD-L1 prevalence and expression by VENTANA SP142 immune cell immunohistochemistry (IHC; cutoff 1%) was also investigated within and across the cohorts. Results: As compared to local BCs, 31 genes were significantly enriched for genomic alterations in BMs with BM prevalence >3% and false-discovery rate (FDR) Table 1.Prevalence (%) of the genomic signatures HRD-gLOH, TMB, MSI and PD-L1+ expression.Site% HRD-gLOH% TMB-H% MSI-H% PDL1+ALLlocal BC33.70%. (2573/7636)5.04%. (527/10464)0.37%. (39/10464)54.25%. (1092/2013)BM52.01%. (362/696)15.51%. (116/748)2.01%. (15/748)38.73%. (55/142)N-CNS31.55%. (3237/10260)9.82%. (1395/14210)0.23%. (32/14210)26.21%. (615/2346)ER+/HER2-local BC31.48%. (119/378)3.41%. (19/557)0.36%. (2/557)40.00%. (14/35)BM43.17%. (79/183)11.40%. (22/193)1.04%. (2/193)23.08%. (9/39)N-CNS29.65%. (126/425)8.92%. (51/572)0.17%. (1/572)12.99%. (10/77)ER+/HER2+local BC19.57%. (9/46)2.78%. (2/72)0.00%. (0/72)42.86%. (3/7)BM26.67%. (16/60)9.68%. (6/62)0.00%. (0/62)27.27%. (3/11)N-CNS47.37%. (18/38)19.57%. (9/46)0.00%. (0/46)14.29%. (1/7)ER-/HER2+local BC32.26%. (10/31)8.70%. (4/46)0.00%. (0/46)100.00%. (5/5)BM33.33%. (23/69)21.33%. (16/75)2.67%. (2/75)57.14%. (4/7)N-CNS34.38%. (11/32)4.26%. (2/47)0.00%. (0/47)42.86%. (3/7)ER-/HER2-local BC52.25%. (186/356)2.70%. (14/518)0.19%. (1/518)50.00%. (30/60)BM70.45%. (174/247)17.41%. (47/270)2.59%. (7/270)48.33%. (29/60)N-CNS43.52%. (84/193)10.04%. (27/269)0.74%. (2/269)21.43%. (6/28) Citation Format: Athina Giannoudis, Ethan Sokol, Shakti H Ramkissoon, Talvinder Bhogal, Kimberly McGregor, Allison Clark, Evangelia D Razis, Rupert Bartsch, Richard SP Huang, Carlo Palmieri. Comprehensive assessment of the genomic landscape of breast cancer brain metastases reveals targetable alterations and genomic signatures relevant to immune-checkpoint and PARP inhibitors [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr PD4-09.
Databáze: OpenAIRE
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