Subcutaneous Adipose Tissue FDG Uptake is Associated with Systemic Inflammatory Indices Independent of Primary-Tumor...

Adipose tissue may contribute to systemic inflammation in breast cancer. This study evaluated whether visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) [18F]fluorodeoxyglucose ([18F]FDG) uptakes on positron emission tomography/computed tomography (PET/CT) are associated with inflammatory indices after adjustment for PET-derived tumor metabolic burden and whether metastatic status modifies these associations.

In this retrospective single-center cohort (n = 358) undergoing baseline [18F]FDG PET/CT, metastatic status was defined using an internal three-level clinical stage grouping: early-stage or locally advanced disease was classified as M0 and metastatic disease was classified as MET. VAT and SAT FDG uptakes were quantified as z-scored mean standardized uptake values normalized to lean body mass (SULmean) using the James lean body mass equation. Inflammatory indices from complete blood counts were log-transformed. Prespecified linear regression models with heteroskedasticity-consistent type 3 (HC3) robust standard errors were adjusted for age, body mass index (BMI), fasting glucose, stage, molecular subtype, and PET-derived primary-tumor metabolic burden metrics. Effect modification was tested via exposure × MET interaction. Sensitivity analyses used total-body tumor burden metrics in MET and recalculated SUL using the Janmahasatian lean body mass equation; overall survival (OS) was explored with Cox models.

Of 358 patients, 284 (79.3%) were M0 and 74 (20.7%) were MET. In M0 (complete-case n = 267), higher SAT uptake was independently associated with higher log-transformed neutrophil-to-lymphocyte ratio (log(NLR)) (β = 0.0798; 95% confidence interval (CI) 0.0130-0.1466; p = 0.019). In pooled interaction models (n = 323), SAT remained associated with log(NLR) (β = 0.0892; 95% CI 0.0196-0.1588; p = 0.012; ≈9% higher NLR per 1-standard deviation (SD)), with no evidence of effect modification by metastatic status (SAT × MET interaction p = 0.594). Results were consistent after total-body tumor-burden adjustment in MET and after recalculation of SUL using the Janmahasatian lean body mass equation. SAT was not significantly associated with OS (adjusted hazard ratio (HR) = 1.086; 95% CI 0.864-1.364; p = 0.481; n = 346).

Higher SAT FDG uptake was modestly associated with higher NLR independent of tumor metabolic burden, with no evidence of heterogeneity by metastatic status. These findings suggest a potential tissue-specific imaging correlate of host inflammatory phenotype rather than a stand-alone clinical biomarker. Sensitivity and survival analyses remain hypothesis-generating and require external validation.