Abstract P5-08-04: Bioscore: A novel staging system for breast cancer patients receiving neoadjuvant chemotherapy
Authors: Mittendorf EA , Vila J , Tucker SL , Chavez-MacGregor M , Smith BD , Symmans WF , Sahin AA , Hortobagyi GN , Hunt KK 
Published: May 2016

Abstract
Background: We previously described a novel breast cancer staging system, the CPS+EG score, which incorporates pretreatment clinical stage, post-treatment pathologic stage, estrogen receptor (ER) status and nuclear grade to create an ordinal scale that is predictive of disease-specific survival (DSS) after receipt of neoadjuvant chemotherapy. The prior work predated (1997-2005) routine use of trastuzumab for patients with HER2+ disease. The current study was undertaken to update the staging system with a more contemporary cohort of patients to include patients with HER2+ disease receiving trastuzumab. The impact of using 1% as the cutoff for ER-positivity was also assessed.
Methods: A cohort of 2377 patients treated with neoadjuvant chemotherapy from 2005-2012 was identified. Clinicopathologic characteristics, treatment regimens and patient outcomes were recorded. Patient scores were computed using two versions of the CPS+EG staging system with ER status categorized as positive if &gt;10% or if &gt;1%. Fits of the Cox proportional hazards (PH) model for the two sets of prognostic scores were compared using the Akaike Information Criterion (AIC). HER2 status was then added to the model and the likelihood ratio test was used to determine the improvement in fit.
Results: Median follow-up time was 4.2 years (range, 0.5 to 11.7). Five year DSS was 89% (95% CI: 87%-90%). This cohort validated our previous finding that the CPS+EG score facilitates more refined categorization into prognostic subgroups than initial clinical or final pathologic stage alone (table). The AIC demonstrated that the CPS+EG model fits were nearly identical for ER status categorized using either cutoff, though the fit was slightly better for the &gt;1% cutoff. There were 591 HER2+ patients included; all of them received trastuzumab-based chemotherapy. The improvement in the fit of the model when HER2 status was added was highly significant (p=0.00005) and incorporation of HER2 into the CPS+EG staging system by adding one additional point for HER2-negative status defined the bioscore (table) which again stratified patients with respect to prognosis.
Conclusion: The current study demonstrates a novel bioscore that significantly improves a previously validated prognostic score in patients receiving neoadjuvant chemotherapy and allows the staging system to be applied to patients with HER2+ disease. We recommend that biologic markers and response to treatment be incorporated into the forthcoming revision of the AJCC staging system.
Clinical Stage5-yr DSS (95%CI)Pathologic Stage5-yr DSS (95%CI)CPS+EG Score (1% cutoff for ER+)5-yr DSS (95%CI)Bioscore5-yr DSS (95%CI)0 097% (95-98%)098% (92-100%)097% (78-10)%)IA96% (75-99%)IA95% (92-97%)198% (96-99%)199% (95-100%)IIA96% (94-97%)IB90% (76-98%)294% (91-95%)297% (95-98%)IIB90% (87-92%)IIA91% (87-94%)387% (84-90%)393% (90-95%)IIIA85% (80-89%)IIB86% (81-90%)475% (69-80%)486% (82-89%)IIIB78% (70-85%)IIIA80% (75-84%)552% (40-63%)571% (64-77%)IIIC76% (70-81%)IIIB64% (42-80%)60648% (35-60%) IIIC64% (55-72%) 70
Citation Format: Mittendorf EA, Vila J, Tucker SL, Chavez-MacGregor M, Smith BD, Symmans WF, Sahin AA, Hortobagyi GN, Hunt KK. Bioscore: A novel staging system for breast cancer patients receiving neoadjuvant chemotherapy. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P5-08-04.