Prognostic Nutritional Index as a Predictor of Mortality Risk in Breast Cancer Survivors: A Population-Based Study

Background: The Prognostic Nutritional Index (PNI) is widely utilized to evaluate nutritional and inflammatory status in predicting cancer prognosis, yet its impact on mortality among breast cancer patients remains incompletely understood. This study aimed to assess the association between PNI and all-cause as well as cancer-specific mortality in breast cancer survivors. Material and methods: Data were retrieved from the National Health and Nutrition Examination Survey (NHANES) covering the period 2005 to 2018. A cross-sectional study design was employed to examine the association between PNI and breast cancer prevalence, with a cohort design utilized for mortality follow-up. Moreover, weighted logistic regression was applied to quantify the relationship between PNI and breast cancer survivor status. Multivariate Cox proportional hazards models, restricted cubic spline (RCS) analysis, and two-piecewise Cox proportional hazards models were used to evaluate the correlations of PNI with all-cause mortality and cancer-specific mortality. Finally, subgroup analyses were performed to validate the robustness. Results: A total of 16,688 participants were ultimately enrolled. Among 479 female breast cancer survivors, 122 all-cause deaths occurred during follow-up, including 43 cancer deaths (median 6.21 years). After multivariate adjustment, RCS analysis revealed non-linear relationships, with inflection points: 46 for all-cause and cancer-specific mortality. When PNI < 46, higher PNI significantly reduced all-cause mortality (HR = 0.74, 95% CI: 0.64 - 0.86, P < 0.001) and cancer-specific (HR = 0.34, 95% CI: 0.20 - 0.58, P < 0.001). When PNI ≥ 46, the association between elevated PNI and the risk of all-cause mortality (HR = 0.97, 95% CI: 0.89 - 1.06, P = 0.489) as well as cancer-specific mortality (HR = 1.04, 95% CI: 0.84 - 1.28, P = 0.741) was no longer statistically significant. The final subgroup analysis further supported the robustness of the results. Conclusions: PNI was nonlinearly associated with mortality in breast cancer survivors. Its threshold facilitates risk stratification, and a PNI below this threshold increases the risk of both all-cause and cancer-specific mortality. However, this specific finding requires validation in larger cohorts due to substantial statistical uncertainty.