Validation of a Risk Score Incorporating Tumor Characteristics into the American Joint Committee on Cancer Anatomic Stage for Breast Cancer

PURPOSE: The American Joint Committee on Cancer 8th edition (AJCC8) prognostic stage (PS) was implemented January 1, 2018, but it is complex due to multiple permutations. A North American group proposed a simpler system using the anatomic stage with a risk score system (RSS) of 1 point each for grade 3 tumor and human epithelial growth factor receptor 2 (HER2) and estrogen receptor (ER) negativity. Here we aimed to evaluate this risk score system with our database of Asian breast cancer patients and compare it against the AJCC8 PS. METHODS: Patients diagnosed with breast cancer stage I–IV in 2006–2012 were identified in the SingHealth Joint Breast Cancer Registry. Five-year breast cancer-specific survival (CSS) and overall survival (OS) were calculated for each anatomic stage according to the risk score and compared with the AJCC8 PS. RESULTS: A total of 6,656 patients were analyzed. The median follow-up was 61 (interquartile range, 37–90) months. There was a high receipt of endocrine therapy (84.6% of ER+ patients), chemotherapy (84.3% of node-positive patients), and trastuzumab (86.0% of HER2+ patients). Within each anatomic stage, there were significant differences in survival in all sub-stages except IIIB. On multivariate analysis, the hazard ratio for negative ER was 1.74 (1.48–2.06), for negative HER2 was 1.49 (1.26–1.74), and for grade 3 was 1.84 (1.55–2.19). On multivariate analysis controlled for age, ethnicity, and receipt of chemotherapy, the RSS (Akaike information criterion [AIC] = 10,649.45; Harrell's Concordance Index [C] = 0.85) was not inferior to the AJCC8 PS (AIC = 10,726.65; C = 0.84) for CSS, nor was the RSS (AIC = 14,714.4; C = 0.82) inferior to the AJCC8 PS (AIC = 14,784.69; C = 0.81) for OS. CONCLUSION: The RSS is comparable to the AJCC8 PS for a patient population receiving chemotherapy as well as endocrine- and HER2-targeted therapy and further stratifies stage IV patients.