Abstract P2-07-02: A newly derived combined clinical treatment score and immunohistochemical-4 prognostic tool
Authors: Dodson A , Sestak I , Bayani J , Dowsett M , Bartlett J , Cuzick J 
Published: May 2019

Abstract
AIM
To determine whether a modified Clinical Treatment Score (CTS) based on continuous tumor size and 5 lymph node categories provided more prognostic information in an independent test set than the original CTS with and without the Immunohistochemical-4 (IHC4) algorithm for prediction of residual distant recurrence risk over 10-years.
BACKGROUND
Risk of recurrence information in patients with estrogen receptor-positive (ER+), early breast cancer informs decision-making on chemotherapy use. The CTS and IHC4 algorithms provide such information, particularly when used in combination (IHC4+C). Their derivation in the translational cohort of the Arimidex Tamoxifen Alone or in Combination trial (TransATAC) was described by Cuzick et al in 2011. In the original model tumor size and nodal status were each classified into three categories, causing prognostic information to be lost.
METHODS
We modeled a novel CTSn algorithm on outcome data from patients in the anastrozole and tamoxifen arms in ATAC incorporating tumor size as a continuous variable and sub-dividing nodal status into five categories. IHC4n was re-derived in the TransATAC cohort independent of CTSn. Patients were chemotherapy-naïve. We compared ability to predict risk of residual distant recurrence of the new IHC4n+Cn model with that of the original one when tested in a training cohort and in a validation set of chemotherapy-naïve patients from the Tamoxifen vs. Exemestane Adjuvant Multicentre (TEAM) trial using Cox regression models and the C-index.
RESULTS
The ATAC training set for CTSn comprised 4056 patients, the TransATAC training set for IHC4n comprised 1125 patients; 2591 patients were in the TEAM validation set. Patients in the TEAM set were older (median age in TransATAC: 63.5, TEAM: 68.3 years), had a higher nodal-burden (node-positive in TransATAC: 29.4%, TEAM: 51.8%) and had more Grade 3 tumors (TransATAC: 18.3%, TEAM: 32.2%).
The new IHC4n+Cn was significantly prognostic, and non-significantly more prognostic than the original IHC4+C in both the training and validation cohorts. When assessed using the C-index statistic, IHC4n+Cn had a higher discriminatory ability than the original algorithm (Table 1).
Table 1 TransATAC (N=1125)TEAM (N=2591) HR* (95% CI)C-indexHR* (95% CI)C-indexOld Models CTS2.26 (2.01-2.53)0.6811.88 (1.73-2.03)0.650IHC41.67 (1.46-1.91)0.6301.49 (1.35-1.63)0.604IHC4+C2.76 (2.40-3.18)0.7242.03 (1.87-2.21)0.671New Models CTSn2.64 (2.26-3.09)0.7212.16 (1.96-2.39)0.687IHC4n1.74 (1.52-2.01)0.6421.51 (1.36-1.68)0.603IHC4n+Cn2.91 (2.47-3.42)0.7382.28 (2.06-2.51)0.695(*Hazard Ratio for change in one Standard Deviation).
CONCLUSION
By separately remodellng the part of the IHC4+C score based on clinicopathological characteristics using the whole ATAC chemo-naïve cohort, and the part that uses IHC-derived information in chemo-naïve TransATAC patients, we increased the precision of the individual risk estimates produced by both CTSn and IHC4n compared to those given by the original algorithms. The new IHC4n+Cn shows a trend for improved prognostic ability compared to the original IHC4+C. Like its predecessor, it relies on information that is readily available to clinicians and integrates it in an evidence-based way to improve prognostication in ER+ early breast cancer.
Citation Format: Dodson A, Sestak I, Bayani J, Dowsett M, Bartlett J, Cuzick J. A newly derived combined clinical treatment score and immunohistochemical-4 prognostic tool [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P2-07-02.