Pre-frailty and frailty as independent predictors of mortality in U.S. breast cancer survivors: Evidence from the national health interview survey, 1997 to 2018

Frailty is increasingly recognized as a determinant of poor outcomes in cancer survivorship, yet its prognostic value among breast cancer survivors remains unclear, particularly for pre-frailty. We analyzed data from 22 waves of the national health interview survey (1997–2018), linked to the national death index, encompassing 625,128 adults, including 9941 breast cancer survivors and 615,187 cancer-free participants. Frailty was assessed using a modified fatigue, resistance, ambulation, illness, and loss of weight scale and categorized as robust (score 0), pre-frail (score 1–2), or frail (score 3–5). Kaplan–Meier methods and log-rank tests evaluated survival differences, and Cox proportional hazards models estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for all-cause mortality, adjusting for sociodemographic, clinical, and cancer-related covariates. Among breast cancer survivors, 78.3% were robust, 13.1% pre-frail, and 8.6% frail, compared with 88.7%, 6.3%, and 5.0% among cancer-free participants. Kaplan–Meier analyses revealed significant survival differences across frailty categories (log-rank P < .001). In fully adjusted models, pre-frailty (HR, 1.44; 95% CI, 1.39–1.51) and frailty (HR, 1.70; 95% CI, 1.49–1.94) were both independently associated with increased mortality relative to robust survivors. Associations were consistent in women and in survivors aged ≥60 years. Among survivors younger than 60 years, frailty remained a strong predictor of mortality (HR, 2.46; 95% CI, 1.52–4.00), whereas pre-frailty did not reach statistical significance. In the small subgroup of male survivors, frailty was not significantly associated with mortality, likely due to limited sample size. Both pre-frailty and frailty independently predict mortality in breast cancer survivors. Systematic frailty screening and targeted interventions may improve survivorship outcomes.