Food Insecurity and Overall Survival in Locally Advanced Breast Cancer Patients Receiving Comprehensive Nodal Irradiation: The Food Insecurity–Obesity Paradox

Residents of food-insecure areas (FIAs) experience worse cancer outcomes, but underlying mechanisms remain poorly understood. Prior studies have not determined whether inequalities result from differences in cancer characteristics, treatment delivery, adherence, or food insecurity (FI) itself. We hypothesized that patients with locally advanced breast cancer (LABC) residing in FIAs would demonstrate worse overall survival (OS) despite receiving similar cancer treatments with comparable treatment adherence. This retrospective study analyzed 943 patients with LABC treated with comprehensive nodal irradiation from 2016 to 2023. χ2 and Mann-Whitney U tests assessed differences in demographic, clinical, and treatment variables. Kaplan-Meier analysis and multivariable Cox regression models evaluated OS. Median follow-up was 25.0 months for non-FIA and 28.8 months for FIA residents. FIA residents (n = 60; 6.4%) were more likely to identify as Black (P < .001), and have comorbidities including hypertension (P < .001), diabetes mellitus (DM; P < .001), and higher ECOG PS (P <.001). Although categorical obesity rates did not differ between groups at consultation (57.4% vs 42.3%; P = .153), they diverged significantly by follow-up (65.5% vs 40.9%; P < .001). Cancer and treatment characteristics did not differ between groups. Multivariable analysis identified FI (HR, 5.52; 95% CI, 1.76-17.27; P = .003), diabetes mellitus (HR, 2.96; 95% CI, 1.13-7.76; P = .027), and new pulmonary conditions at follow-up (HR, 9.57; 95% CI, 3.46-26.49; P < .001) as independent predictors of mortality. Hormone therapy delivery (HR, 0.12; 95% CI, 0.02-0.95; P = .045) and duration (HR, 0.96; 95% CI, 0.94-0.98; P < .001) were protective. Five-year OS was 74.9% for FIA versus 90.2% for non-FIA residents (P = .005). Patients with LABC residing in FIAs had a 5.5 times higher mortality risk despite similar cancer characteristics, treatments, and adherence. Higher obesity rates among FIA residents that increased following treatment represent a novel characterization of the FI-obesity paradox in patients with breast cancer. These findings support residence in an FIA as an independent predictor of mortality and suggest that interventions must address nutritional quality and access.