Breast Cancer Prognostication by Pathologic Node Staging (pN-staging) System Versus Lymph Node Ratio (LNR): A Critical Review of Conflicts With Number of Nodes, Z-0011 Trial , Staging Cut-points, Neo-adjuvant Therapy, and Survival Estimation

Background: The AJCC pN-staging system is the current risk stratification strategy for axillary nodal staging in most cancer centers. Recently, another staging system named "Lymph Node Ratio" or LNR has been developed and also postulated to have prognostic value. Precise prognostication of breast cancer by these two systems has multiple methodological dilemmas which are overlooked in the literature and still remain matters of debate. Methods: These two issues are categorized into seven queries, including: the number of nodes considered adequate for proper axillary staging; attitude toward Z-0011 trial; impacts of neo-adjuvant therapies; the origin and evolution of stratification cutoffs; the position where patients without axillary involvement should be placed; role of diverse endpoints in survival definition, outcome analyses and prognosis prediction; and ultimately the current opinion regarding the superiority between the two systems. This review sought to explore these topics through analysis of 58 recently published articles found by MEDLINE search. Results: The analysis revealed that precise prognostication by pN-staging system requires at least 10 excised-nodes, but LNR system minimally depends on the quantity of excised-nodes. Adhering to Z-0011 trial findings obstructs the provision of sufficient nodes for pN-staging. Neo-adjuvant chemotherapy alters the axillary nodal climate and therefore disrupts proper axillary staging. Cutoffs of LNR system have a more clear history of formation than the pN-staging's. Breast cancer-specific survival is the type of survival better portraying cancer-related events. Conclusions: LNR system seems at least as accurate as pN-staging in prognostication of breast cancer patients.