Abstract P5-01-03: Stratifying triple-negative breast cancer prognosis using 18F-FDG-PET/CT imaging
Authors: Yue Y , Cui X , Bose S , Audeh W , Zhang X , Fraass B 
Published: May 2016

Abstract
Introduction: Triple-negative breast cancer (TNBC) is a highly diverse group of cancers, and may benefit from molecular-targeted therapies. This study aims to stratify prognosis of TNBC patients using pre-treatment 18F-FDG PET/CT, alone and with correlation to immunohistochemistry biomarkers.
Method: 200 consecutive TNBC breast cancer patients treated between 2008 and 2012 who received lumpectomy or mastectomy as primary treatment were retrieved. Among the full cohort, 79 patients had pre-treatment 18F FDG PET/CT scans. Immunostaining status (percentage and intensity) of basal biomarkers (EGFR, CK5/6), Ki-67, P53, and other clinicopathological variables (age, tumor size, pathological T/N stage, nuclear grade, and lymph node metastasis) were obtained. Three PET image features were evaluated: maximum uptake values (SUVmax), mean uptake (SUVmean) and target volume (SUVvol) defined by SUV&gt;2.5. The relationships among tumor metabolic activities and clinicopathological factors were evaluated. All variables were analyzed versus disease-free survival (DFS) using univariate and multivariate Cox analysis, Kaplan-Meier curves and log-rank tests. The optimal cutoff points of variables were estimated using time-dependent survival receiver operating characteristic (ROC) analysis.
Results: All PET features significantly correlated with proliferation marker Ki-67 (all p&lt;0.010). SUVmax stratified the prognosis of TNBC patients with optimal cutoff derived by ROC analysis (≤3.5 vs &gt;3.5, AUC=0.654, p=0.006). Basal biomarkers EGFR and CK5/6 and image features SUVmax, SUVmean, SUVvol were significant associated with DFS in univariate Cox analysis, whereas SUVmax (p=0.001) and EGFR (p=0.001) were also significant in multivariate Cox analysis. To integrate prognosis of biological and imaging markers, patients were first stratified by EGFR into low (≤15%) and high (&gt;15%) risk groups. Further, SUVmax was used as a variable to stratify the two EGFR groups. In the high EGFR group, patients with high FDG uptake (SUVmax&gt;3.5) had worse survival outcome (median DFS=7.6 months) than those patients with low FDG uptake (SUVmax≤3.5, median DFS=11.6 months). In the low EGFR group, high SUVmax also indicated worse survival outcome (17.2 months) than low SUVmax (22.8 months). The risk stratification with integrative EGFR and PET was statistically significant with log-rank p&lt;&lt;0.001.
Multivariate Cox analysis for disease-free survivalVariablesHR (95% CI)p-valuePathology, T stage, ≤ 3 vs &gt;32.337(0.428-7.384)0.148EGFR, ≤15% vs &gt; 15%9.109(1.997-41.55)0.004CK5/6, ≤ 50% vs &gt; 50%1.471(0.598-3.614)0.401SUVmax, ≤3.5 vs &gt; 3.53.883(1.13-13.32)0.031
TNBC patient risk groups stratified by EGFR and SUVmax (with the median values of variables)Risk groups (EGFR&gt;15, SUVmax&gt;3.5)patient#DFS monthsEGFR %SUVmaxSUVmeanSUVvolKi-67%1 (-, -)1222.852.00.60.2342 (-, +)1517.258.94.37.2673 (+, -)1311.6502.72.60.9354 (+, +)377.66011.35.210.960
Conclusions: Pre-treatment 18F-FDG PET/CT imaging has significant prognostic value for predicting survival outcome of TNBC patients. Integrated with basal-biomarker EGFR, PET imaging can further stratify patient risks in the pre-treatment stage, and help select appropriate treatment strategies for individual patients.
Citation Format: Yue Y, Cui X, Bose S, Audeh W, Zhang X, Fraass B. Stratifying triple-negative breast cancer prognosis using 18F-FDG-PET/CT imaging. [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 P5-01-03.