Abstract
Rationale and ObjectivesNormal-appearing stromal tissues surrounding breast tumors can harbor abnormalities that lead to increased risk of local recurrence. The objective of this study was to develop a new imaging methodology to characterize the signal patterns of stromal tissue and to investigate their association with recurrence-free survival following neoadjuvant chemotherapy.Materials and MethodsFifty patients with locally-advanced breast cancer were imaged with dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) before (V1) and after one cycle (V2) of adriamycin-cytoxan therapy. Contrast enhancement in normal-appearing stroma around the tumor was characterized by the mean percent enhancement (PE) and mean signal enhancement ratio (SER) in distance bands of 5 mm from the tumor edge. Global PE and SER were calculated by averaging all stromal bands 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.ResultsThe mixed effects model displayed a decreasing radial trend in PE at both V1 and V2. An increasing trend was less pronounced in SER. Survival analysis showed that the hazard ratio estimates for each unit decrease in global SER was statistically significant at V1 [estimated hazard ratio = 0.058, 95% Wald CI (0.003, 1.01), likelihood ratio p = 0.03]; but was not so for V2.ConclusionsThese findings show that stromal tissue outside the tumor can be quantitatively characterized by DCE-MRI, and suggest that stromal enhancement measurements may be further developed for use as a potential predictor of recurrence/disease-free survival following therapy.
Highlights
The evolution of breast cancer requires co-optation of the surrounding stromal tissues to facilitate progression and support metabolic demand
Survival analysis showed that the hazard ratio estimates for each unit decrease in global signal enhancement ratio (SER) was statistically significant at V1 [estimated hazard ratio = 0.058, 95% Wald CI (0.003, 1.01), likelihood ratio p = 0.03]; but was not so for V2
These findings show that stromal tissue outside the tumor can be quantitatively characterized by dynamic contrast-enhanced magnetic resonance imaging (DCE-magnetic resonance imaging (MRI)), and suggest that stromal enhancement measurements may be further developed for use as a potential predictor of recurrence/disease-free survival following therapy
Summary
The evolution of breast cancer requires co-optation of the surrounding stromal tissues to facilitate progression and support metabolic demand. This has been shown in the earliest stages of breast cancer, ductal carcinoma in situ (DCIS), where proliferating malignant cells inside the breast duct are associated with a remodeled stroma outside of the duct, characterized in part by increased angiogenesis and microvessel density [1]. Subsequent development of a segmentation technique has allowed automatic quantification of stromal enhancement measures, voxel-by-voxel relative to the distance to the tumor [8] When applied, this tool demonstrated that the peak stromal enhancement was elevated in regions surrounding invasive breast tumors and was associated with increased microvessel density [9]. We applied our more advanced tissue mapping technique to validate the previous findings and to determine whether MR enhancement in the stromal tissue could be a predictor for recurrence-free survival following neoadjuvant chemotherapy
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