Abstract P1-10-09: The MHCII immune activation assay is prognostic for disease free survival in basal-like TNBC breast cancer patients in the GEICAM/9906 clinical trial
Authors: Martín Miguel , Updike Katherine L , Rodríguez-Lescure Alvaro , Calvo Lourdes , Herranz Jesús , Martín Nuria , Bernard Philip S , Varley Katherine E 
Published: March 2020

Abstract
Background: Approximately 40% of patients with stage I-III triple-negative breast cancer (TNBC) recur after standard treatment, while the remaining 60% experience long-term disease-free survival (DFS). There are currently no clinical tests to assess the risk of recurrence in TNBC patients. We previously developed and validated an MHCII Immune Activation assay, which measures a gene expression signature that includes the major histocompatibility complex class II (MHCII) pathway genes and markers of activated tumor infiltrating lymphocytes. The MHCII Immune Activation assay was recently shown to accurately assess the risk of recurrence in Basal-like TNBC patients using FFPE tissues from an institutional cohort. A limitation of the previous study is that the patients’ treatment regimens in the institutional cohort were heterogeneous. The goal of this study was to determine if the MHCII Immune Activation assay can accurately assess the DFS in Basal-like TNBC patients who received uniform chemotherapy regimens in the context of a randomized clinical trial. Methods: The MHCII Immune Activation assay was applied to RNA isolated from 60 Basal-like TNBC FFPE specimens from the GEICAM/9906 clinical trial, a multicenter randomized phase III study evaluating adjuvant chemotherapy in node-positive operable BC patients. Thirty nine (65%) of the patients were treated with fluorouracil, epirubicin, and cyclophosphamide (FEC), and 21 (35%) patients received FEC followed by paclitaxel (FEC-P) (median follow-up 9.7 years). The MHCII Immune Activation Score was calculated from the assay using methods described previously, and patients were categorized into a High Risk of Recurrence (High ROR) group using pre-specified thresholds. The association between the MHCII Immune Activation Score and DFS was assessed using Kaplan-Meier analysis and cox proportional hazards models. Results: Across both arms, 32/60 (53.3%) patients were classified into the High ROR group based on their Low MHCII Immune Activation Scores. Patients in the High ROR group had significantly shorter DFS (Hazard Ratio (HR)=2.9 (CI95%:1.27-6.66), p-value=0.0081). Cox proportional hazard regression of the log10 transformed MHCII Immune Activation Score confirmed that MHCII Immune Activation Score is significantly associated with DFS (Wald Test p=0.0127). In the FEC arm, there were 22/39 (56.41%) patients classified into the High ROR group (Low MHCII Immune Activation Score). Patients in the High ROR group in the FEC arm showed a trend toward shorter DFS (HR=1.99 (CI95%:0.74-5.31)), but it was not significant (p-value=0.1595). In the FEC-P arm, there were 10/21 (47.62%) patients classified into the High ROR group (Low MHCII Immune Activation Score). Patients in the High ROR group in the FEC-P arm had significantly shorter DFS (HR=6.28 (CI95%:1.28-30.73), p-value=0.0111). Larger cohorts will be needed to confirm if the association between DFS and MHCII Immune Activation Score is stronger when patients are treated with chemotherapy regimens that include paclitaxel. Conclusions: The MHCII Immune Activation assay can be applied to RNA from FFPE tumor specimens to assess risk of recurrence in TNBC patients. The MHCII Immune Activation Score is associated with risk of recurrence in TNBC patients treated with uniform adjuvant chemotherapy regimens.
Citation Format: Miguel Martín, Katherine L Updike, Alvaro Rodríguez-Lescure, Lourdes Calvo, Jesús Herranz, Nuria Martín, Philip S Bernard, Katherine E Varley. The MHCII immune activation assay is prognostic for disease free survival in basal-like TNBC breast cancer patients in the GEICAM/9906 clinical trial [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P1-10-09.