The purpose of this study was to assess whether MR contrast-enhancement in healthy stromal tissue of the breast is able to further stratify survival of patients considered to be at high risk according to prognostic models derived from the tumor. In 415 patients with pathology proven unilateral invasive ER+HER2- breast cancer, the contralateral parenchymal enhancement was automatically extracted. Contralateral parenchymal enhancement appears to complement existing prognostic models derived from the tumor. In patients at high risk according to conventional prognostic models or molecular assays, contralateral parenchymal enhancement was able identify a subgroup with a relative good survival.
After approval of the institutional review board and written informed patient consent, 415 patients with pathology proven unilateral invasive ER+HER2- breast cancer were consecutively included for a retrospective analysis. The patients participated in the MARGINS study (2000–2008), were eligible for breast conserving therapy, and were consecutively recruited for an additional preoperative breast MRI. MR images were acquired using a Siemens 1.5 T scanner. An unenhanced T1-weighted image was acquired, and after injection of gadolinium containing contrast four consecutive post-contrast series were acquired 90 s apart. The imaging parameters were: repetition time/echo time: 8.1/4.0 ms, flip angle: 20°, voxel size: 1.35 × 1.35 × 1.35 mm3.
On the MR images, the contralateral stromal tissue was segmented using the previously published method(Figure 1).8 The post-contrast images were registered to the pre-contrast images using deformable registration to compensate for patient motion.9 The late parenchymal enhancement was calculated using (S(t4)- S(t1)) / S(t1), where S(t1) was the signal at the first post-contrast scan and S(t4) at the last post-contrast scan. The average of the top-10% most enhancing voxels was defined as contralateral parenchymal enhancement (CPE). This is an unitless value that can be compared between patients. Analysis was performed for overall survival (OS) in patients at high risk according to four existing prognostic models: the Nottingham Prognostic Index (NPI, where NPI > 3.4 is considered high risk); the Dutch guidelines for chemotherapy (Table 1); the 70-gene signature; and the 21-gene signature.1,3,4,10 For each population, CPE was dichotomized on the median. Kaplan-Meier estimators and log-rank tests were used to investigate the relation between CPE and OS.
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