54P Comparison of ctDNA profiles in lobular vs NST hormone receptor-positive metastatic breast cancer patients in early lines of treatment

As the most common special subtype of breast cancer (BC), invasive lobular carcinoma (ILC) displays different clinical and histological features, especially in the metastatic setting. As ILC is frequently hormone receptor-positive (HR+), HER2 negative (HER2-), we compared ctDNA in patients with stage IV ILC to patients with stage IV HR+, HER2- BC with non-special type (NST). From an initial cohort of 84 HR+/HER2- patients with metastatic breast cancer we selected 77 patients diagnosed with NST, N=61, or ILC, N=16. We analyzed circulating tumor DNA (ctDNA) from plasma samples before initiating first or second-line endocrine-based therapy. Tumor fractions were estimated using mFAST-SeqS, an untargeted aneuploidy detection method, and presented as z-scores. Additionally, the AVENIO ctDNA Expanded 77-gene panel was used to characterize the mutational landscape of ctDNA across histologies. For this analysis, we included single nucleotide variants (SNVs) classified as pathogenic, likely pathogenic, or of unknown significance. Analysis revealed that84% (65/77) of patients had detectable ctDNA alterations. The percentage did not significantly differ between patients with NST vs ILC (94% for ILC and 82% for NST, p=0.441). Although ctDNA from patients with ILC demonstrated a higher median z-score than that from patients with NST, the difference did not reach statistical significance (median 3.32 vs. 1.85, p=0.112). Patients with ILC had a significantly higher number of SNVs than those with NST (median 4.0 vs. 2.5; p=0.042). No differences in mutant allele frequency were noted. Among metastatic NST cases, the most prevalent alterations were in PIK3CA (38%), TP53 (26%), ESR1 (20%), PTEN (11%), and BRCA1 (10%). For ILC, the predominant alterations were in PIK3CA (56%), AR (19%), EGFR (19%), ESR1 (19%), and KDR (19%). Although PIK3CA, AR, and EGFR alterations were more common in ILC than in NST, these differences were not statistically significant (all p>0.05). In ILC, PIK3CA, AR, and EGFR alterations and higher z-scores were more common but did not reach statistical significance. The numbers of SNV were significantly higher in patients with ILC.