The combined pN stage and breast cancer subtypes in breast cancer: a better discriminator of outcome can be used to refine the 8th AJCC staging manual.

BACKGROUND: pN stage and breast cancer subtypes (BCS) are both well-recognized prognostic indicators. Our previous work has highlighted that patients even with the same pN stage exhibited a significant survival difference in different BCS. Given this achievement, we hypothesized that a statistical interaction might exist between pN stage and BCS. The aim of this retrospective cohort study was to compare the prognostic value of the combined pN stage and BCS (pNnew stage) with either pN stage or BCS alone, and to determine if this combined new stage could serve as an alternative discriminator of outcome. METHODS: We combined pN stage and BCS to create a new variable named pNnew stage and then divided it into four groups: pN0new, pN1new, pN2new, and pN3new. Survival analysis was performed with the use of the Kaplan-Meier method and the log-rank test was used for univariate analysis. For multivariate analysis, cox proportional hazard models were applied, allowing for the estimation of disease-free survival (DFS). To assess discriminatory accuracy of the models, we compared the area under the receiver-operating characteristic curve (AUROC), the Akaike information criterion (AIC), and the Bayesian information criterion (BIC) values. Then, we used this pNnew stage to generate a TNnewM staging system according to the 7th AJCC staging system. RESULTS: A statistical interaction between pN stage and BCS was found. In multivariate survival analysis, the pNnew stage has been confirmed as an independent prognostic variable of 5-year DFS. The pNnew stage, with a smaller AIC or BIC value and larger AUROC, was a more powerful predictor of DFS than either pN stage or BCS alone. Results were validated in a separate cohort of patients. The TNnewM stage proposed in our present study was found comparable to the new 8th AJCC edition which includes anatomic T, N, and M plus tumor grade and the status of the biomarkers Her-2, ER, and PR with respect to prognostic value for breast cancer patients. CONCLUSIONS: The pNnew stage (combined pN stage and BCS) appears to be a more powerful predictor and discriminator for the outcome of breast cancer, as compared to pN stage or BCS alone, and the TNnewM stage may serve as a simple, easy-to-use alternative to the 8th AJCC edition staging manual.