Abstract Background: Bone metastases (mets) develop in 50-70% of patients with metastatic breast cancer (MBC) and are associated with significant morbidity due to skeletal-related events (SREs), associated with significant decline in quality of life. Of the 180, 000 patients living with MBC in the United States, 30-45% have bone mets as their only site of disease (‘bone-only’/BO-MBC). Patients with BO-MBC are frequently excluded from clinical trials because bone mets are not ‘measurable. ’ In a large nationwide cohort, using the FoundationOne®Liquid CDx circulating tumor DNA (ctDNA) assay we previously demonstrated that ctDNA was just as likely to be detected and ctDNA tumor fraction (TF) remained prognostic in patients with BO-MBC. We hypothesize that ctDNA TF in combination with PET-CT will provide superior monitoring of bone mets. Methods: In this contemporaneously enrolled, retrospectively analyzed study, patients with any hormone receptor subtype receiving any line of systemic therapy undergoing standard-of-care PET-CT were identified for blood collection within 37 days of each PET-CT for ctDNA analyses. Patients were categorized as BO or bone-lymph node (BO/L-MBC) versus bone mets + visceral mets (BV-MBC) based on disease status. Plasma was banked from 20mL of blood collected at the time of clinical blood draws and underwent analysis by the laboratory developed test FoundationOneMonitor ctDNA assay for research assessment of ctDNA TF (accounting for aneuploidy, variant allele frequency, fragment length, clonal hematopoiesis CH and genomic alterations for 324 genes at each timepoint). PET-CT scans were deidentified and reviewed by a study radiologist on VISAGE PACS to determine SUVmax (PET Maximum Standardized Uptake Value) plus number of skeletal/non-skeletal lesions. Outcome measures included progression-free survival (PFS) and time to next therapy (TTNT). Results: A total of 42 patients (21 BO/L-MBC, 21 BV-MBC) completed a total 160 PET-CT SUVmax change: ANOVA p=0. 002). When evaluating TF change from T1: T2, patients whose TF remained increased (relative to stable or declined) had significantly shorter PFS (hazard ratio HR 3. 7, 95% confidence interval CI 1. 7-7. 8, log-rank p0. 001) and TTNT (log-rank p0. 001). When evaluating BO/L-MBC cohort whose first PET-CT imaging was ‘stable’, patients whose TF increased (relative to stable or declined) had significantly shorter PFS (HR 8. 6, 95% CI 1. 6-47, log-rank p=0. 008). Detailed evaluation of specific genomic alterations revealed expansion of known resistance mutations (including ESR1, ERBB2, and PTEN) in advance of imaging and clinical progression. Conclusion: In patients with BO/L-MBC, ctDNA TF change was significantly associated with PFS and TTNT, even in the setting of PET-CT imaging interpreted as ‘stable. ’ ctDNA sequencing offers a clinically useful adjunct to clinical imaging for bone-metastatic MBC, with the potential to expand the definition of measurability to include those with BO-/L-MBC. Citation Format: D. Veney, H. LeFebvre, L. Wei, G. Bader, M. Cherian, A. Davenport, M. Gatti-Mays, K. Johnson, S. Sardesai, R. Wesolowski, N. Williams, K. Shanahan, V. Prasath, B. To, K. Hoskova, M. Childress, J. C. F. Quintanilha, R. P. Graf, M. Levy, L. W. Pasquina, E. Kubi-Appiah, D. G. Stover. P-climb: pet-ct and liquid biopsy for monitoring breast cancer bone metastasis abstract. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32 (4 Suppl): Abstract nr PS4-03-02.
Veney et al. (Tue,) studied this question.