Utility of plasma circulating DNA tumor fraction in bone-only metastatic breast cancer: a real-world outcomes study.

Purpose: Bone metastases develop in 50-70% of patients with metastatic breast cancer (MBC), with around one-third having bone as only site of distant disease (bone-only [BO]). Standard imaging is frequently insufficient to track bone metastases. Evidence suggests that circulating tumor DNA (ctDNA) tumor fraction (TF) is prognostic in MBC. We hypothesized that TF would be detectable and prognostic for BO-MBC.

Methods: MBC patients who underwent FoundationOne LiquidCDX comprehensive genomic profiling within 60 days before starting therapy were included. Clinical data was obtained from the nationwide deidentified Flatiron Health/Foundation Medicine Clinico-Genomic Database between 01/2011 and 12/2023.

Results: We identified 778 patients for inclusion: 299 TF < 1% (TF-low), 175 TF 1-10% (TF-intermediate [int]), 304 TF > 10% (TF-high). Of these, 155 had BO-MBC, 622 had non-BO MBC (1 missing metastasis data). Among samples collected prior to first-line therapy (n = 256), there was no significant difference in the proportion of patients with detectable ctDNA comparing BO-MBC to non-BO MBC patients (P = 1.0). TF was prognostic among patients with BO-MBC: TF-low demonstrated more favorable real-world overall survival (rwOS) relative to TF-int (hazard ratio [HR] 2.19, 95% confidence interval [CI] 1.1-4.35) and TF-high (HR 2.07, 95% CI 1.12-3.82; log-rank P = 0.027). Multivariable analyses confirmed the independent and additive association of TF and less favorable rwOS. In multivariable analyses evaluating clinicopathologic factors associated with TF, non-BO metastases were not associated with higher ctDNA TF.

Conclusion: BO-MBC patients are as likely as non-BO-MBC to have detectable ctDNA and TF remains prognostic among BO-MBC patients, with TF < 1% associated with significantly better prognosis.