Abstract P4-01-04: MRI enhancement in stromal tissue surrounding breast tumors: Association with RFS following neoadjuvant chemotherapy
Authors: Jones EF , Sinha SP , Newitt D , Klifa C , Kornak J , Park CC , Hylton NM 
Published: August 2014

Abstract
Objective: Stromal tissue surrounding breast tumors can harbor abnormalities that predict increased risk of recurrence. The purpose of this study was to evaluate low-level contrast enhancement patterns in normal appearing breast stroma surrounding tumors using dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). A secondary objective was to investigate whether enhancement patterns varied with distance from tumor and whether proximity-dependent enhancement was associated with recurrence-free survival following neoadjuvant chemotherapy (NACT).
Materials and Methods: Sixty-three patients with locally-advanced breast cancer were imaged with DCE-MRI before (V1) and after one cycle (V2) of adriamycin-cytoxan (AC) therapy. Normal-appearing stromal tissue on MR images was defined as fibroglandular tissue outside of tumor regions. Fibroglandular tissue was segmented from pre-contrast T1-weighted images using a fuzzy C-means clustering method1. Tumor regions were identified using a percent enhancement threshold of 70% in the first post-contrast image (PE1). Distance from tumor (proximity) was defined for each stromal voxel as the minimum three-dimensional distance from any tumor voxel. Stromal enhancement was characterized by calculating mean PE and mean signal enhancement ratio (SER = PE1/PE2) in distance shells of 5 mm, from 0 to 40 mm outside of tumor tissue. Global PE and SER were calculated by averaging all stromal voxels from 5 to 40 mm from tumor. Proximity-dependent PE and SER were analyzed using a linear mixed effects model and Cox proportional hazards model for recurrence-free survival.
Results: The mixed effects model displayed a decreasing radial trend in PE at both V1(estimated mean = −0.39 per mm, 95% CI (−0.50, −0.29), p &lt; 0.0001) and V2 (estimated mean = −0.34 per mm, 95% CI (−0.56, −0.13), p = 0.002). The trend was less pronounced in SER and did not achieve statistical significance (V1, p = 0.12; V2 p = 0.11). For the recurrent group, there was a marginal trend of lower global SER at V1 (estimated difference of −0.07, 95% CI (−0.13, 0.01) two-tail Wilcoxon-Mann-Whitney U-test, p = 0.11) but not at V2 (estimated difference in location of −0.04, 95% CI (−0.11, 0.26), p = 0.4). There was no evidence for a clear difference in PE for recurrent verses non-recurrent patients at either visit. Survival analysis with average PE or SER as predictors showed that although PE provided no detectable predictive power at V1 and V2, the SER hazard ratio estimates for each unit decrease in SER was marginally statistically significant at 11.5, 95% CI (0.85, 155), p = 0.07 for V1; but was not so for V2: estimate = 0.85, 95% CI (0.04, 20), p = 0.9.
Conclusions: These findings show that stromal tissue outside the primary tumor can be quantitatively characterized by DCE-MRI, and suggest that stromal enhancement measurements may be worth exploring as a potential predictor of recurrence/disease-free survival following NACT.

Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P4-01-04.