MRI Enhancement in Stromal Tissue Surrounding Breast Tumors: Association with Recurrence Free Survival following Neoadjuvant Chemotherapy

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Abstract

Rationale and Objectives:Normal-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 Methods:Fifty 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.Results:The 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.Conclusions:These 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. © 2013 Jones et al.

Figures

  • Figure 1. Patient inclusion/exclusion flow chart.
  • Figure 2. Signal intensity-time curve for DCE-MRI. Signal intensity-time curve for DCE-MRI showing early (PE1) and late (PE2) percent enhancement measurements. S0, S1, and S2 represent the signal intensity of images obtained at t0 (before contrast injection), t1 (2.5 minutes after contrast injection), and t2 (7.5 minutes after contrast injection), respectively. Three curves display different patterns of signal increase and washout: 1) the blue curve shows a slow gradual increase in enhancement, more characteristic of normal tissue; 2) the green curve shows an early enhancement with little washout, essentially a plateau in signal intensity; 3) the red curve shows a pattern of early enhancement with a fast washout, which is more characteristic of highly vascularized tissues. doi:10.1371/journal.pone.0061969.g002
  • Figure 3. Proximity mapping of breast tumor. The proximity mapping method takes the difference of the segmentation of tumor (a) and fibroglandular map (b) to create a 3-dimensional stromal proximity map (c). The stromal proximity map is then applied to the functional image to calculate proximity-dependent values. doi:10.1371/journal.pone.0061969.g003
  • Table 1. Patient and Tumor Characteristics.
  • Figure 4. Radial trend of PE in recurrent and non-recurrent patients. Radial trends of PE values in recurrent and non-recurrent groups (based on a 5-year cut off) were shown here over a distance of 5 to 40 mm from the tumor edge. A decreasing trend (shown in red trend line) of PE was observed in all cases (3a–d). doi:10.1371/journal.pone.0061969.g004
  • Figure 5. Stromal enhancement pattern of SER in recurrent and non-recurrent patients. Stromal enhancement pattern of SER in recurrent and non-recurrent cohorts at V1 and V2 (based on a 5-year cut-off). The red line shows the trending of SER. At V1: there was no observable trend for recurrent group (a) but an increasing trend of stromal SER outside of tumor was observed in the non-current group (b). At V2: No observable trend was found in the recurrent group (c), but a slight increasing trend was found in the non-recurrent group (d). doi:10.1371/journal.pone.0061969.g005

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CITATION STYLE

APA

Jones, E. F., Sinha, S. P., Newitt, D. C., Klifa, C., Kornak, J., Park, C. C., & Hylton, N. M. (2013). MRI Enhancement in Stromal Tissue Surrounding Breast Tumors: Association with Recurrence Free Survival following Neoadjuvant Chemotherapy. PLoS ONE, 8(5). https://doi.org/10.1371/journal.pone.0061969

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