Abstract GS3-07: The genomic landscape of breast cancer based on ctDNA analysis: Data from the plasmaMATCH trial

Background: Circulating tumor DNA (ctDNA) is found in the plasma of over 90% of patients with advanced breast cancer (BC). ctDNA analysis can establish the current genomic profile of an individual’s cancer and identify potentially targetable mutations. The genomic landscape of advanced BC and clinical associations has yet to be fully defined. This analysis describes the genomic landscape of ctDNA in patients screened for the UK plasmaMATCH study. Methods: The plasmaMATCH trial was an open-label, multi-centre, multi-cohort platform trial, consisting of ctDNA testing in ~1000 patients with advanced BC. The trial consists of parallel treatment cohorts (Cohorts A-E) with therapies matched to mutations identified in ctDNA testing. The genomic landscape of ctDNA in advanced BC was prospectively analysed for hotspot PIK3CA,AKT1, HER2 and ESR1 mutations using digital droplet PCR (ddPCR, Bio-Rad), and using an error-corrected 73-gene targeted panel (Guardant360, Guardant Health) prospectively from part-way through the trial, and retrospectively for the remaining patients. Results: Entry into ctDNA testing for Cohorts A-D was closed on 26/Apr/2019, at which time 1044 patients had been registered and 1025 tested with ddPCR. 800 patients had targeted panel ctDNA sequencing (364 prospective, 436 retrospective) (Table 1). Targeted sequencing identified a somatic alteration in 92.9% of patients (743/800). The most frequent mutations were TP53 (44.1%), PIK3CA (34.9%), ESR1 (33.1%), GATA3 (11.0%) and ARID1A (7.8%). ESR1 (33.1%) and KRAS (4.1%) alterations occurred at higher frequency in ctDNA compared to a metastatic tissue sequencing series (q Genomic AlterationddPCR*Targeted Panel**All % n = 1025HR+ HER2-% n = 658HR+ HER2+ % n = 62HR- HER2+ % n = 36TNBC % n = 172All % n = 800HR+ HER2- % n = 515HR+ HER2+ % n = 48HR- HER2+ % n = 26TNBC % n = 136PIK3CA mutation25.829.933.919.49.334.939.041.734.614.7ESR1 mutation27.737.819.40033.143.522.900.7AKT1 mutation4.24.01.604.75.05.22.104.4ERBB2 mutation2.73.208.31.26.46.612.515.42.2PTEN mutationNANANANANA6.98.54.23.84.4ERBB2 amplificationNANANANANA5.81.931.357.71.5MSI highNANANANANA1.10.42.101.5* Phenotype data based on 928 patients with known phenotype tested by ddPCR for targetable hotspot mutations.** Phenotype data based on 725 patients with known phenotype sequenced by targeted panel. All pathogenic mutations are shown, including mutations not tested by ddPCR. Citation Format: Belinda Kingston, Hannah Bye, Michael Hubank, Giselle Walsh, Claire Swift, Matthew Beaney, Lucy Kilburn, Sarah Kernaghan, Andrew M Wardley, Iain Macpherson, Richard D Baird, Rebecca Roylance, Katie Wilkinson, Isaac Garcia-Murillas, Judith M Bliss, Nicholas Turner, Alistair Ring, on behalf of the plasmaMATCH Trial Management Group. The genomic landscape of breast cancer based on ctDNA analysis: Data from the plasmaMATCH trial [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr GS3-07.