Guodong Chen, Wei Lin, Xueliang Cheng, Xin Chang
Accelerated biological ageing is an independent predictor of mortality in breast cancer patients. The distinct time-specific utilities of HD and PA suggest that biological age indicators may guide personalized risk stratification and clinical management.
BACKGROUND AND AIMS: Breast cancer is the most common malignancy in women, and advanced biological ageing correlates with increased incidence. However, the prognostic value of comprehensive biological age biomarkers remains unclear. This study aimed to investigate the association between composite biological age indices and mortality in breast cancer patients.
METHODS: We analyzed data from 399 breast cancer participants in the National Health and Nutrition Examination Survey (1999-2020). Three biological age indicators were calculated using 12 blood-based biomarkers: Phenotypic Age (PA), Homeostatic Dysregulation (HD), and the Klemera-Doubal Method (KDM). Survey-weighted Cox models estimated hazard ratios (HR) for all-cause mortality. Restricted cubic splines assessed linearity, and time-dependent receiver operating characteristic curves evaluated predictive performance.
RESULTS: During a median follow-up of 6.67 years, 144 deaths occurred. In fully adjusted models, higher indices were associated with increased mortality risk: HD (HR = 1.465, 95% CI: 1.169-1.836), KDM (HR = 1.017, 95% CI: 1.004-1.030), and PA (HR = 1.080, 95% CI: 1.023-1.140). Spline analyses confirmed linear associations. ROC analyses revealed a time-stratified predictive capacity, finding that HD performed best for short-term prediction, whereas PA showed superior efficacy for mid- to long-term prognosis.
CONCLUSION: Accelerated biological ageing is an independent predictor of mortality in breast cancer patients. The distinct time-specific utilities of HD and PA suggest that biological age indicators may guide personalized risk stratification and clinical management.