Abstract P6-09-17: Evaluation of a risk score based on biologic factors to enhance prognostic stratification by the American Joint Committee on Cancer (AJCC) Staging System
Authors: Mittendorf EA , Vila J , Yi M , Chavez-MacGregor M , Chen RL , Giordano SH , Hunt KK 
Published: March 2017

Abstract
Background: The 7th edition AJCC staging system provides prognostic information based on the anatomic extent of disease determined by the tumor size (T), lymph node status (N), and presence or absence of metastatic disease (M). Tumor biology, including grade, estrogen receptor (ER) status and HER2 status, which are known to have prognostic and predictive value, are not incorporated. This study was undertaken to evaluate a risk score that takes into account the tumor grade and other biomarkers that can be added to the current anatomic TNM staging system to improve stratification of patients with respect to disease specific survival (DSS) and overall survival (OS).
Methods: A prospectively maintained database was used to identify 3,327 patients with non-metastatic invasive breast cancer who underwent surgery as a first intervention from January 2007 through December 2013. Clinicopathologic data were recorded including: age, grade, ER status, HER2 status, and pathologic stage. Pathologic stage was determined according to the 7th edition of the AJCC staging guidelines. ER status was recorded as the percentage of cells staining positive by immunohistochemistry (IHC). Prior to 2010, tumors were classified as ER positive if there was &gt;10% staining. A cut-off of 1% was used for patients treated after 2010, consistent with the change in American Society of Clinical Oncology (ASCO) guidelines. HER2 status was defined as positive if 3+ on immunohistochemistry or gene amplification was shown on fluorescence in situ hybridization. A risk score was calculated by assigning one point for each of the following tumor characteristics: ER-negative status, HER2 negative status and grade 3. Univariate survival analyses according to AJCC stage (I, IIA, IIB, IIIA and IIIC) and risk score (0-3) were performed for DSS and OS using the Kaplan Meier method.
Results: Median follow-up time was 5.0 years (range, 0.1 to 8.8). Five year DSS for the entire cohort was 97.9% (95% CI: 97.3%-98.4%). The distribution in risk score in the entire cohort was: risk score 0=81 (2.4%), 1=2289 (68.8%), 2=683 (20.5%), and 3= (8.3%). As shown in the table, for all AJCC stages, the 5-yr DSS and 5-yr OS varied according to risk score (p&lt;.01).
StageRisk Scoren5-yr DSS (%)95% CI5-yr OS (%)95% CII (IA and IB)036100 9780.4-99.6 1117399.498.7-99.796.795.4-97.6 227498.896.4-00.694.691.0-06.8 311996.691.1-98.793.887.5-97.0IIA031100 96.879.2-99.5 163499.497.5-99.897.194.7-98.4 223697.593.2-99.194.188.7-97.0 39891.081.8-95.788.278.5-93.8IIB011100 100 130996.992.6-98.894.689.6-97.2 210792.983.6-97.189.380.1-94.4 34091.575.6-97.291.575.6-97.2IIIA03100 100 113498.388.2-99.891.582.6-96.0 25092.277.2-97.590.375.7-96.3 3768.621.3-91.268.621.3-91.2IIIC00 13992.272.1-98.084.463.7-93.9 21680.851.4-93.480.851.4-93.4 31033.36.3-64.633.36.2-64.6
Conclusion: The current study demonstrates that incorporating the risk score with current AJCC staging significantly improves the ability to stratify breast cancer patients with respect to DSS and OS. We recommend that the risk score be incorporated into the forthcoming revision of the AJCC staging system.
Citation Format: Mittendorf EA, Vila J, Yi M, Chavez-MacGregor M, Chen RL, Giordano SH, Hunt KK. Evaluation of a risk score based on biologic factors to enhance prognostic stratification by the American Joint Committee on Cancer (AJCC) Staging System [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P6-09-17.