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 (pN_new 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 pN_new stage and then divided it into four groups: pN0_new, pN1_new, pN2_new, and pN3_new. 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 pN_new stage to generate a TN_newM 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 pN_new stage has been confirmed as an independent prognostic variable of 5-year DFS. The pN_new 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 TN_newM 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 pN_new 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 TN_newM stage may serve as a simple, easy-to-use alternative to the 8th AJCC edition staging manual. [ABSTRACT FROM AUTHOR]