Background: Circulating tumor DNA (ctDNA) can be used as a non-invasive method to detect and quantify genomic alterations (GA) in blood. We evaluated the relationship between ctDNA features, radiographic disease progression (RDP) and progression-free survival (PFS) in patients (pts) with metastatic breast cancer (MBC). Methods: A retrospective analysis of 32 female MBC pts with plasma ctDNA tested prior to a radiology scan was performed. Plasma ctDNA tests were run by Inivata using a 36-gene panel for detecting point mutations, short insertions/deletions, and copy number variations. ctDNA features were tabulated for each pt and included number of genomic alterations (numGA), maximum mutant allele frequency (maxMAF), and sum of mutant allele frequency (sumMAF). Univariate and multivariable logistic regression (LR) models were used to explore ctDNA features associated with RDP. Univariate and multivariable Cox proportional hazards models were used to identify ctDNA features that were associated with PFS. All models included ctDNA features as continuous variables. Results: Frequency of subtypes were 38% HR+HER2-, 28% HR+HER2+, 28% triple-negative, and 6% HR-HER2+. 97% had prior chemotherapy; 92% of HR+HER2-negative pts had prior endocrine therapy. 20 of 32 samples (69%) had GAs. The most common GAs were TP53 (50%), ESR1 (25%), PIK3CA (19%), and GATA3 (9.4%). Median numGA was 1 (0-12); median maxMAF was 1.9 (0-65.5); median sumMAF was 2.2 (0-157.2). Univariate LR analysis identified numGA (p=0.025), maxMAF (p=0.034), and sumMAF (p=0.049) to be significantly associated with RDP; numGA (p=0.056) and maxMAF (p=0.109) were retained in the final multivariable LR model. Univariate Cox regression analysis showed that numGA (HR=1.32, p Conclusions: Blood ctDNA profiling contributes to the prediction of RDP and PFS in MBC pts. High number of alterations and high allele fraction of these alterations were associated with worse clinical outcomes. These data provide an overview of the ctDNA dynamics in treated MBC pts. Citation Format: Tan AR, Symanowski J, Kim EN, Hosking M, Morris CD, Plagnol V, Farhangfar CJ, Ersek JL. Association of circulating tumor DNA with clinical outcomes in metastatic breast cancer patients [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P1-20-06.