52P Comparing the genomic landscape of de novo vs recurrent metastatic breast cancer by ctDNA and tissue profiling

We aimed to describe the molecular landscape of de novo versus recurrent metastatic breast cancer (dnMBC and rMBC). Clinical and molecular data from patients with MBC were collected from the molecular tumour board at Gustave Roussy. Genomic analyses were carried out by liquid or solid biopsies (FoundationOne® Liquid CDx assay and FoundationOne® Tissue CDx, respectively; both covering 324 genes), performed during disease evolution as per investigator choice. Descriptive statistics were performed using R studio version 4.1.1. We identified 668 patients with genomic data, from whom 564 had available clinical data: 464 patients with liquid biopsy (141 dnMBC; 323 rMBC) and 100 (21 dnMBC; 79 rMBC) patients with a tissue-based assay. Overall, there was no significant difference in the median number of mutations (Mut), copy number variants (CNV), rearrangements (Rearrang) or Tumour Mutational Burden (TMB) detected between dnMBC and rMBC. A higher median number of mutations were noted on ctDNA-based assays compared to tissue-based assays (12 versus 9, p-value <0.05). On ctDNA-based assays, 85-100% of patients had at least one alteration detected in both dnMBC and rMBC, regardless of BC subtype. The table summarizes percentage of patients having at least one alteration in breast cancer subtypes. The most frequently altered genes in dnMBC were ATM, ESR1, PIK3CA and TP53on ctDNA; ATM, BRCA2, LTK, PIK3CA and TP53 on tissue. In rMBC, the most frequently altered genes were ATM, CHEK2, ESR1, PIK3CA and TP53on ctDNA; ARID1A, BRCA2, MAP3K1, PIK3CA and TP53 on tissue. Differences in genomic landscape between dnMBC and rMBC for each specific subtype will be presented at the congress.Table: 52PdnMBC liquid (%)rMBC liquid (%)dnMBC tissue (%)rMBC tissue (%)TNRearrang4545835CNV26263362Mut89854276Median TMB (mut/Mb)443.783.78HR+/HER2+Rearrang50271000CNV036050Mut1009110050Median TMB (mut/Mb)103.787.57HR-/HER2+Rearrang443300CNV223300Mut8910000Median TMB (mut/Mb)4100HR+/HER2-Rearrang19241517CNV23214554Mut86924564Median TMB (mut/Mb)332.523.78 Open table in a new tab The most commonly altered genes are similar between dnMBC and rMBC. We observed substantial differences in mutational profile assessed by ctDNA vs tissue-based assay.