55P Landscape of PIK3CA, PTEN, and AKT1 alterations in advanced breast cancer (ABC) using circulating tumor DNA (ctDNA): Next generation sequencing (NGS) in Asia and the Middle East (AME)

The phosphatidylinositol 3-kinase-AKT kinasesignaling pathway regulates cell survival, proliferation, and metabolism. Mutations (m) in PIK3CA, PTEN, and AKT1 frequently occur in ABC. The prevalence of m in these genes and associated co-alterations using ctDNA NGS in ABC from AME is unknown. We retrospectively reviewed results of Guardant360 (Guardant Health, Inc.) ordered for patients with ABC from AME as part of routine clinical practice through Jan 2024. Plasma samples were analyzed by NGS at a CLIA-certified, CAP-accredited central laboratory. Prescribing physicians did not routinely provide tumor hormone receptor status or line of testing. Findings were compared to 2 publicly available databases, Memorial Sloan Kettering (MSK)-MET and MSK-HR (https://www.cbioportal.org/). The median age of 1,081 ABC patients tested was 57 years (range 26-101). The median mutation count was 3 (range 1-91), and median variant allelic frequency was 1.4% (range 0.04-83.6%). Prevalence of PIK3CAm was 36%, 35%, and 39% in AME, MSK-MET, and MSK-HR databases, respectively. Types of m were similar across databases, most being H1047X and E545X. TP53, ESR1, and NF1 had the most common co-mutations in all databases. In all databases, microsatellite-high (MSI-H) was observed at a similar rate (around 1%) in PIK3CAm patients. Prevalence of PTENm was 7.6%, 6.9%, and 6.1%, respectively. Across databases, PTEN R130X and T319X were the most common mutations. Most frequent co-mutations in all databases were in TP53, PIK3CA, and ESR1. 1.3% of patients with PTENm had MSI-H in the AME database only. AKT1m occurred in 5.9%, 5.1%, and 7.6% of patients. The distribution of specific AKT1m was similar among databases, with E17K being the most frequent. Most frequent co-mutations were in TP53, ESR1, and GATA1 in all databases. 1.5% of patients with AKT1m had MSI-H in the AME database only. To our knowledge, this is the first AME-specific dataset illustrating that ctDNA NGS can identify PIK3CAm, PTENm, AKT1m, and co-alterations that may inform therapeutic decisions for patients with ABC. Our results indicate a similar prevalence of these mutations in AME and other regions.