Complementary value of contralateral parenchymal enhancement on DCE-MRI to prognostic models and molecular assays in high-risk ER+HER2- breast cancer

van der Velden, Bas H M, Elias, Sjoerd G, Bismeijer, Tycho, Loo, Claudette E., Viergever, Max A, Wessels, Lodewyk F A, Gilhuijs, Kenneth G A


Clinical Cancer Research 23 (21), p. 6505-6515


PURPOSE: To determine whether markers of healthy breast stroma are able to select a subgroup of patients at low risk of death or metastasis from patients considered at high risk according to routine markers of the tumor.

EXPERIMENTAL DESIGN: Patients with ER-positive/HER2-negative breast cancer were consecutively included for retrospective analysis. The contralateral parenchyma was segmented automatically on dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI), whereupon the average of the top-10% late enhancement was calculated. This contralateral parenchymal enhancement (CPE) was analyzed with respect to routine prognostic models and molecular assays (Nottingham Prognostic Index, Dutch clinical chemotherapy-selection guidelines, 70-gene signature, and 21-gene recurrence score). CPE was split in tertiles and tested for overall and distant disease-free survival. CPE was adjusted for patient and tumor characteristics, as well as systemic therapy, using inverse probability weighting (IPW). Subanalyses were performed in patients at high risk according to prognostic models and molecular assays.

RESULTS: Four-hundred-and-fifteen patients were included, constituting the same group in which the association between CPE and survival was discovered. Median follow-up was 85 months, 34/415(8%) patients succumbed. After IPW-adjustment for patient and tumor characteristics, patients with high CPE had significantly better overall survival than those with low CPE in groups at high risk according to the Nottingham Prognostic Index (HR(95%CI):0.08(0.00-0.40),P<.001); Dutch clinical guidelines (HR(95%CI):0.22(0.00-0.81),P=.021); and 21-gene recurrence score (HR(95%CI):0.14(0.00-0.84),P=.030). One group showed a trend (70-gene signature:HR(95%CI):0.25(0.00-1.02),P=.054).

CONCLUSIONS: In patients at high risk based on the tumor, subgroups at relatively low risk were identified using pretreatment enhancement of the stroma on breast DCE-MRI.