Abstract PS1-10-16: Longitudinal genomic profiling of circulating tumor DNA in metastatic invasive lobular (ILC) and no special type (NST) breast cancer

Abstract Background Liquid biopsy enables minimally invasive cancer monitoring through blood circulating tumor DNA (ctDNA) sequencing. We analyzed ctDNA sequencing data of 127 blood samples from 27 patients with hormone receptor positive (HR+) metastatic invasive lobular breast carcinoma (ILC) and 10 patients with HR+ no special type/invasive ductal carcinoma (NST/IDC) from the UPMC Hillman Cancer Center APOLLO biobank collection. In APOLLO collection, patients’ blood is collected at each disease progression, enabling longitudinal analysis of ctDNA dynamics. In this study, we focused on longitudinal analysis of ctDNA dynamics in patients with ILC. Methods We analyzed 31 longitudinal NST samples (2-6 per patient, median 3) and 96 ILC samples (2-7 per patient, median 3). DNA was extracted from plasma and sequenced using shallow whole genome sequencing, with a mean coverage of 0.21x. We used ichorCNA to determine the tumor fraction (TFx) of samples, and used CNVkit to annotate gene level copy number variation (CNV) and filtered with a list of genes that have most frequent copy number aberration in breast cancer. GISTIC2.0 was applied to compare chromosomal segment aberration of ILC and NST cases. Gene level CNVs were collapsed to each patient, and continuity index (1 - [number of transition/maximum possible transitions]) was applied to measure the longitudinal consistency of gene CNVs. Results Patients with ILC had a median overall survival of 43 months (range 6-124 months) with a median of 5 treatment lines (range 2-11). IchorCNA analysis showed 85 samples (91.4%) had TFx >3% (mean TFx 12.5%). Tumor fraction fluctuates across time, and shows correlation with the patient treatment scheme. Patient-level analysis demonstrated predominant copy number gains (copy number ≥3) versus losses (copy number