Obesity-associated host factors and intracranial disease phenotype in breast cancer brain metastases.

Abstract

e14030 Background: Obesity is characterized by chronic low-grade systemic inflammation and altered metabolic signaling, which may disrupt periphery-to-brain communication and compromise central nervous system interfaces. These obesity-associated inflammatory perturbations may influence tumor seeding and the phenotypic presentation of brain metastases (BrM). However, the relationship between body mass index (BMI) and intracranial disease phenotype and outcomes in patients with BrM remains poorly defined. Methods: We conducted a retrospective cohort study of patients with breast cancer and BrM with BMI recorded within one year prior to or ≤1 month after BrM diagnosis. The primary endpoint was overall survival (OS) from BrM diagnosis. BMI was analyzed as a continuous variable (per 5 kg/m² increase) and categorically (BMI ≥30 vs <30 kg/m²). Multivariable Cox regression models for OS and intracranial progression-free survival (iPFS) were adjusted for age at BrM diagnosis, receptor-defined subtype (hormone receptor (HR)+/HER2−, HER2+, triple negative breast cancer (TNBC)), Karnofsky performance status, leptomeningeal disease (LMD), intracranial disease burden, local brain-directed therapy, and systemic therapy at BrM diagnosis. Logistic regression evaluated associations between BMI and disease characteristics. In exploratory analyses patients with BMI documented within one year of early breast cancer, time to BrM was evaluated using an accelerated failure time model adjusted for age and subtype. Results: Among 277 patients with BMI at BrM diagnosis, median age was 54.3 years; 109 (41.9%) had HR+/HER2− disease, 84 (32.3%) HER2+, and 67 (25.8%) TNBC. Sixty-four patients (23.3%) were obese (BMI ≥30 kg/m²). Higher BMI was associated with numerically higher intracranial disease burden (adjusted OR per 5 kg/m²: 1.09, 95% CI 0.81–1.78, p=0.677) and lower odds of LMD at presentation (adjusted OR per 5 kg/m²: 0.85, 95% CI 0.56–1.11, p=0.356), although these associations were not statistically significant. BMI was not associated with OS (adjusted HR per 5 kg/m²: 0.99, 95% CI 0.80–1.22, p=0.909) or iPFS (adjusted HR: 0.88, 95% CI 0.70–1.11, p=0.292). When BMI was categorized, moderate and high BMI groups showed numerically shorter OS compared with BMI <25 kg/m², not statistically significant. In exploratory analyses of 142 patients, BMI was not associated with time to BrM among patients with early-stage breast cancer (adjusted time ratio per 5 kg/m²: 1.02, 95% CI 0.91–1.15). Conclusions: Higher BMI at the time of BrM diagnosis was associated with a distinct intracranial disease phenotype, including non-significant differences in disease burden and leptomeningeal involvement, but was not significantly associated with intracranial progression or OS. These findings suggest that host metabolic status may contribute to heterogeneity in BrM and warrants further investigation.