A novel staging system for disease-specific survival in patients with breast cancer treated with surgery as the first intervention.

Abstract

92 Background: American Joint Committee on Cancer (AJCC) staging of breast cancer is used to determine prognosis, yet survival of patients within each stage shows wide variation and remains unpredictable. We hypothesized that differences in underlying biology might influence some of this variation and that the addition of biologic markers to current AJCC staging parameters would improve predictions of prognosis. Methods: We identified an initial cohort of 3,728 patients at our center who underwent surgery as the first intervention between 1997 and 2006. We used a Cox proportional hazards model, with backward stepwise exclusion of factors and stratified on pathologic stage (PS), to test the added significance of modified Black’s nuclear grade (G), the presence of lymphovascular invasion (L), estrogen receptor status (E), progesterone receptor status (P), or combined ER and PR status (EP), or combined receptor subtype (ER+PR+HER2 [M]). We assigned values 0-2 to these disease-specific survival (DSS)–associated factors and then used different combinations to assess different staging systems. Surveillance Epidemiology and End Results (SEER) data was used as the external cohort (n=26,711) to validate the scoring system. Results: Median follow-up time for the initial cohort was 6.5 years, and the 5-year DSS rate was 97.4%. Six different staging systems were used to predict 5-year patient outcomes: PS, PS+G, PS+GL, PS+EG, PS+GEP, and PS+GM. We compared 5-year DSS rates, Akaike’s information criterion (AIC) and Harrell’s concordance index (C-index) for each staging system. We found that the PS+GEP staging system was most precise with lowest AIC (1927.3) and had the highest C-index (0.80). The ability of the PS+GEP system to stratify outcomes was confirmed in the internal bootstrapping samples and the external validation cohort. Conclusions: Our results validate a new staging system that incorporates tumor grade, ER and PR status into current AJCC staging for breast cancer. We recommend that biologic markers be incorporated into revised versions of the AJCC staging system for patients undergoing surgery as their first intervention.