Association of Systemic Inflammatory Indices With Breast Cancer: A Cross-Sectional Analysis of National Health and Nutrition Examination Survey (NHANES) Data

Background: Breast cancer remains one of the leading causes of cancer-related morbidity and mortality among women worldwide. Systemic inflammatory indices derived from routine hematological parameters, including NLR, PLR, and SII, have recently gained attention as potential biomarkers associated with breast cancer risk and progression. However, population-based evidence evaluating these inflammatory markers after adjustment for demographic, socioeconomic, and lifestyle-related confounders remains limited. Aim: We evaluated the association of systemic inflammatory indices, including NLR, PLR, and SII, with self-reported history of breast cancer in a nationally representative cross-sectional population sample after adjustment for demographic, socioeconomic, and lifestyle-related factors. Methods: This cross-sectional analytical study utilized data from the NHANES 2021-2023 cycle. Female participants aged ≥18 years with available complete blood count parameters and breast cancer status information were included. Breast cancer status was defined using self-reported physician diagnosis. NLR, PLR, and SII were calculated from hematological parameters obtained through standardized laboratory assessment. Demographic, socioeconomic, and lifestyle variables included age, body mass index (BMI), race/ethnicity, poverty-income ratio (PIR), smoking history, and alcohol intake. Due to non-normal distribution, continuous variables were summarized as median (interquartile range) and compared using Mann-Whitney U tests. Categorical variables were analyzed using Rao-Scott adjusted chi-square tests accounting for the NHANES complex survey design. Multivariable survey-weighted logistic regression models were constructed separately for NLR, PLR, and SII, adjusting for potential confounders. Adjusted odds ratios (aORs) with 95% confidence intervals (CIs) were reported, and p < 0.05 was considered statistically significant. Results: A total of 5,298 women were included, of whom 150 (weighted prevalence ~1.9%) reported a history of breast cancer. Women with breast cancer were older than those without breast cancer. Exploratory unweighted descriptive comparisons showed higher median NLR, PLR, and SII values among participants with breast cancer compared with controls. However, after adjustment for demographic, socioeconomic, and lifestyle factors in survey-weighted multivariable models, none of the inflammatory indices demonstrated an independent association with breast cancer. Age consistently remained the strongest independent predictor of breast cancer across all models (p < 0.001). Conclusion: Although exploratory unweighted analyses demonstrated higher inflammatory index values among women with breast cancer, these associations were not independently significant in survey-weighted multivariable models.