Objective:

To examine the association between the Framingham Steatosis Index (FSI) and prevalent breast cancer in women using NHANES data.

Approach:

• Study Design: Cross-sectional analysis of female participants in NHANES 1999–2018.
• Statistical Analysis: Multivariable logistic regression models evaluated the association between FSI and prevalent breast cancer, with additional analyses for non-linearity and threshold effects.
• Exploratory Dataset: An exploratory hospital-based dataset was analyzed to assess the association in a different clinical setting.

Key Findings:

• Among 21,042 women, 531 (2.5%) reported a history of breast cancer.
• Each 1-unit increase in FSI was associated with higher odds of prevalent breast cancer (OR 1.10, 95% CI 1.05–1.16), but this association was attenuated after adjusting for age (OR 1.02, 95% CI 0.96–1.07).
• Higher FSI quartiles were associated with greater odds of prevalent breast cancer.
• Restricted cubic spline analysis suggested a non-linear association.
• In the exploratory dataset, FSI was positively associated with breast cancer case status when modeled continuously.

Interpretation:

Higher FSI was associated with prevalent breast cancer status in women, but the association diminished after adjusting for age, indicating that FSI reflects metabolic-hepatic burden rather than serving as an age-independent marker.

Limitations:

• Cross-sectional design precludes causal inference.
• The association may be influenced by confounding factors not accounted for in the analysis.

Conclusion:

FSI should be interpreted as a composite marker of metabolic-hepatic burden rather than as a direct causal biomarker for breast cancer.