Refining breast cancer prognosis by incorporating age at diagnosis into clinical prognostic staging: introduction of a novel online calculator

Purpose American Joint Committee on Cancer (AJCC) clinical staging is used to estimate breast cancer prognosis, but individual patient survival within each stage varies considerably by age at diagnosis. We hypothesized that the addition of age at diagnosis to the staging schema will enable more refined risk stratification. Methods We performed a retrospective population analysis of adult women diagnosed with invasive breast cancer between 2010 and 2015 registered in SEER. Multivariable Cox hazards models were used to evaluate the association of AJCC 8th edition clinical prognostic stage (CPS) and age with risk of overall mortality. Separate hierarchical models were fit to the data: Model 1: CPS alone; Model 2: CPS + age + age 2 ; and Model 3: CPS + age + age 2 + CPS x age + CPS x age 2 . Models were compared by the Akaike information criterion (AIC), the c-statistic for time-dependent receiver operator characteristic curves, and category-free net reclassification improvement (NRI). Internal validation was performed using bootstrapping samples. Results Among 86,637 women, the median follow-up was 36 months and 3-year overall survival was 91.9% ± 0.1%. Age significantly modified the effect of CPS on survival (p