Fatty liver index and breast cancer risk: age-stratified findings from a prospective electronic health record–based cohort

Background The fatty liver index(FLI) is a validated noninvasive marker derived from routinely collected clinical parameters. It is widely used to assess hepatic steatosis and metabolic dysfunction. These conditions have been linked to cancer development. The association between the FLI and breast cancer risk remains limited. Methods We conducted a prospective analysis of a population based cohort with linked electronic health records. We classified participants into low, intermediate, and high FLI groups. We used modified Poisson regression with robust variance to estimate relative risks of incident breast cancer across index categories. We applied Cox proportional hazards models to estimate hazard ratios while adjusting for demographic, metabolic, lifestyle, and reproductive factors. Lifestyle factors were measured using electronic biosensing devices. We used restricted cubic spline models to evaluate non linear dose response relationships. We also performed analyses stratified by age and menopausal status. Multiple sensitivity analyses assessed the stability of the results. Results During follow-up, higher FLI levels were consistently associated with an increased incidence of breast cancer. Compared with women in the low FLI group, those in the intermediate FLI group had an adjusted RR of 1.09 (95% CI, 1.02–1.16) and an HR of 1.08 (95% CI, 1.01–1.15), while those in the high FLI group had an adjusted RR of 1.11 (95% CI, 1.01–1.21) and an HR of 1.11 (95% CI, 1.02–1.21). Restricted cubic spline analyses demonstrated a non-linear association, with a steeper increase in breast cancer risk at higher FLI values. Associations were more pronounced among older and postmenopausal women. Conclusions An elevated FLI derived from routinely available electronic health record data is independently associated with a modest increase in breast cancer risk. This association is more evident among older and postmenopausal women. The FLI may serve as a practical marker for breast cancer risk stratification in population health settings. Further research is needed to clarify underlying mechanisms and to evaluate prevention strategies informed by the FLI.