Histologic Grade Remains a Prognostic Factor for Breast Cancer Regardless of the Number of Positive Lymph Nodes and Tumor Size: A Study of 161 708 Cases of Breast Cancer From the SEER Program

Context.— The appropriate staging of breast cancers includes an evaluation of tumor size and nodal status. Histologic grade in breast cancer, though important and assessed for all tumors, is not integrated within tumor staging. Objective.— To determine whether the histologic grade remains a prognostic factor for breast cancer regardless of tumor size and the number of involved axillary lymph nodes. Design.— By using a new clustering algorithm, the 10-year survival for every combination of T, N, and the histologic grade was determined for cases of breast cancer obtained from the Surveillance, Epidemiology, and End Results Program of the National Cancer Institute. There were 36 combinations of TN, defined according to the American Joint Committee on Cancer, and grade. Results.— For each combination of T and N, a categorical increase in the histologic grade was associated with a progressive decrease in 10-year survival regardless of the number of involved axillary lymph nodes or size of the primary tumor. Absolute survival differences between high and low grade persisted despite larger tumor sizes and greater nodal involvement, though trends were apparent with increasing breast cancer stage. Statistical significance depended on the number of cases for each combination. Conclusions.— Histologic grade continues to be of prognostic importance for overall survival despite tumor size and nodal status. Furthermore, these results seem to indicate that the assignment of the histologic grade has been consistent among pathologists when evaluated in a large data set of patients with breast cancer. The incorporation of histologic grade in TNM staging for breast cancer provides important prognostic information.