1710P Genomic landscape (GL) with potential of methylthioadenosine phosphorylase (MTAP) loss in clinically advanced breast cancer (CABC)

Homozygous deletion of MTAP causes intracellular arginine accumulation enabling anti-tumor effects MTA2/PRMT5 inhibitors via a synthetic lethality mechanism. 7,301 cases MBC underwent hybrid-capture based comprehensive genomic profiling (CGP). Tumor mutational burden (TMB) was determined on up to 1.1 Mb sequenced DNA and MSI status 114 loci. cell PD-L1 expression by IHC (Dako 22C3). 208 (2.84%) CABC featured loss. loss patients were younger (p=.002) more frequently ER- (30% v 50%; p<.0001), triple negative (TNBC) (47% 27%; p<.0001) less HER2+ (2% 8%; p=.0001) than intact MBC. Lobular histology CDH1 mutations frequent in (14%) (p<.0001). CDKN2A (100%) CDKN2B (97%) (9p21 co-deletion) significantly associated with Likely the increased TNBC cases, BRCA1 mutation also (10% 4%; p<.0001). There no clear pattern for predictive Immuno-Oncology (IO) drug biomarkers higher TMB > 20 mut/Mb levels found (p<.0001) low (1-49%% TPS) cases.Table: 1710PCases intactCases lossNumber7093208Mean age*57.854.5ER+/PR+ Status IHC**70.0%/ 49.0%50.00%/29.90%HER2+ Amplification CGP*7.80%1.92%TNBC Status*27.00%47.28%TP53*51.7061.30CDKN2A**3.10100.00CDKN2B**1.3096.70CDH1*14.300.90PTEN*13.1021.70PIK3CA**36.823.60BRCA1**3.709.90ERBB2 amplification*7.801.92ERBB2 sequence mutation*11.206.60EGFR *2.605.20MSI HighFrequency0.03%0.05%cases tested7077205TMB 10%/>20%7.84%/7.40%5.32%/0.96%PD-L1 Positive IC 22C3)Low (1-49%)*11.45%42.90%High (> 50%)2.86%0.00%*Significant (P<0.05), **(P<0.0001). Open table new tab *Significant is ER-, HER2- status, features distinctive GL potential impact both targeted immunotherapies enables emerging clinical trials testing MTA2 PRMT5 CABC.