Abstract P6-08-15: Deconstructing the TNM staging system for breast cancer
Authors: Patel Jigar A , Hueman Matthew T , Chen Dechang , Henson Donald E 
Published: May 2015

Abstract
Background
The TNM staging system is a standard classification for recording extent of disease in breast cancer. However, with progress in understanding tumor biology, it is unknown how new prognostic factors that will eventually be integrated with the TNM will affect its predictive ability. Our objective was to show the impact on 10-year survival rates for breast cancer as different combinations of prognostic factors are integrated into the TNM.
Methods:
Data were obtained from the Surveillance, Epidemiology, and End Results (SEER) Program of the National Cancer Institute for the years 1991 through 2000. After exclusions, 132,339 cases of female breast cancer were available. An ensemble clustering algorithm was used to calculate survival after including additional prognostic factors listed in SEER in the TNM. Combinations of the following 6 factors were sequentially added to the TNM: tumor grade, ER/PR status, age at diagnosis, racial/ethnic group, and histological tumor type.
Results:
Survival rates amongst some tumors with the same TNM stage varied as new factors were integrated into the TNM. Factors associated with favorable outcome usually were associated with better survival than factors associated with less favorable outcome for each stage group with varying degrees. There were 4 different tumor combinations that represented 4 different TNM stages that all corresponded to a 90% 10-year survival when additional factors were added to the TNM stage. Integration of additional prognostic factors led to a crossover in survival of some stage groups. In one combination (T1, N2, grade 1, ER+, PR+, age &lt;50: 131111) patients who were assigned stage IIIA had a 10-year rate of 90%, which qualifies for a stage I category.
Survival Crossover in TNM Staging10-year Survival (%)Prognostic Factor CombinationTNM StageNumber of Patients90113IA1899390112222IA22469021211IIA510190122112IIA40199031111IIB68290131111IIIA82582232221IIB11035822322213IIB92583331111IIIA1285814211111IIIC64**Abbreviated table. Prognostic Factor Combination in order from left to right: T, N, grade, ER status, PR status, age, race, histological type. * T1 = 1; T2 = 2; T3 = 3; N0 = 1; N1= 2; N2 = 3; N3 = 4; Grade 1 = 1; Grade 2 = 2; Grade 3 = 3; ER+ = 1; ER- = 2; PR+ = 1; PR- = 2; Age &lt;= 50 = 1; Age &gt;50 = 2;
Conclusions:
Integrating new prognostic factors into the TNM always changed the outcome. Survival rates, therefore, are relative and depend on the selection of prognostic factors. Adding new factors selected different cohorts from the population which had a heterogeneous population of cancer survivors. These cohorts usually had different survival rates compared with the overall population from which they were drawn. Integrating combinations of prognostic factors revealed frequent crossover of stage groups at 10 years, which is a violation of a staging system and could impact the interpretation of clinical trials.
Citation Format: Jigar A Patel, Matthew T Hueman, Dechang Chen, Donald E Henson. Deconstructing the TNM staging system for breast cancer [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P6-08-15.