Abstract P6-09-35: Proposal for a new breast cancer staging classification: Incorporating clinical and biologic factors
Authors: Murthy RK , Song J , Raghavendra AS , Li Y , Hsu L , Barcenas CH , Tripathy D , Berry D , Hortobagyi GN 
Published: March 2017

Abstract
Background: The current breast cancer staging system, based on anatomy, does not always reflect the variable clinical course outcomes seen in the clinic. Other important and known determinants of prognosis and survival in breast cancer are age, grade, and receptor subtypes. In this analysis, we sought to demonstrate that these additional factors were important determinants of breast cancer specific and overall survival with an intention to propose a new staging classification. Methods: Through a prospectively maintained electronic database at the University of Texas MD Anderson Cancer Center, we identified patients with newly diagnosed invasive breast cancer, stage I-IV, who received surgery as an initial treatment from 1997 to 2014. Data points for the earliest invasive breast cancer event were recorded: age, pathologic stage (7th edition AJCC), grade, ER status, PR status, HER2-neu status, adjuvant treatment history, and outcomes (breast cancer-specific survival [BCSS] and overall survival [OS]). Cox proportional hazards model was used for the statistical analysis. Results: Of 22,131 patients, 99% were women in the following age groups (median age at surgery, 53 years [range, 16-98 years]): age &lt; 40 (13%), 40-69 (76%), &gt;70 (11%). Pathologic stages were: I: 50%, II: 39%, III: 9% and IV: 2%; 768 (3.5%) patients had bilateral breast cancer. Biological subtypes were as follows: Triple-negative (TN): 6%, Hormone receptor-positive/HER2-negative (HR+/HER2-): 70%, HER2-positive (HER2+): 24% (HR+, 9%; HR- 15%). Median follow-up was 7.9 years (95% CI, 7.8-8.0). In multivariate Cox regression modeling, age, grade, and clinical biomarker-based subtypes were significantly associated with breast cancer specific survival (BCSS).
Table 1. Breast cancer specific-survival: Multivariate modelCovariateLevelHR95% CI (p value)Overall p valueAge at DiagnosisLess than 401.521.37-1.68 (&lt;.0001) 40-69Reference&lt;.0001 70-791.050.89-1.24 (0.55) Over 801.150.79-1.66 (0.47)Pathologic StageIAReference&lt;.0001 IIB0.880.58-1.32 (0.54) IIA2.201.96-2.46 (&lt;.0001) IIB3.453.06-3.89 (&lt;.0001) IIIA4.293.70-4.96 (&lt;.0001) IIIB3.432.45-4.79 (&lt;.0001) IIIC6.585.52-7.84 (&lt;.0001) IV15.1212.72-17.96 (&lt;.0001)Biologic SubtypeHR+, HER2-Reference&lt;.0001 HR+, HER2+*0.580.46-0.73 (&lt;.0001) HR-, HER2+*1.100.90-1.35 (0.35) TN**2.001.82-2.21 (&lt;.0001)Nuclear GradeIReference&lt;.0001 II1.731.34-2.23 (&lt;.0001) III3.292.55-4.24 (&lt;.0001)*All patients were treated with trastuzumab in the adjuvant setting **Considering TN as the reference (HR (95% CI): HR+/HER2- (0.50 (0.45-0.55)), HR+/HER2+ (0.29 (0.23-0.37)), HR-/HER2+ (0.55(0.45-0.68). Abbreviations - BCSS: HR: hazard ratio, CI: confidence interval, HR+: hormone receptor positive, HR-: hormone receptor negative, HER2+: Her2-neu positive, HER2-: HER2-neu negative, TN: triple negative, Reference: 1.00
Conclusion: More individualized prediction of outcomes for breast cancer is possible by considering clinical and biologic characteristics in addition to anatomic stage. We intend to integrate pathologic stage, age, and biologic factors into a novel prognostic model to propose a new staging classification for breast cancer.
Citation Format: Murthy RK, Song J, Raghavendra AS, Li Y, Hsu L, Barcenas CH, Tripathy D, Berry D, Hortobagyi GN. Proposal for a new breast cancer staging classification: Incorporating clinical and biologic factors [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 P6-09-35.