Abstract
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+/HER2- breast cancer were consecutively included for retrospective analysis. The contralateral parenchyma was segmented automatically on dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI), where upon 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 < 0.001]; Dutch clinical guidelines [HR (95% CI): 0.22 (0.00-0.81), P = 0.021]; and 21-gene recurrence score [HR (95% CI): 0.14 (0.00-0.84), P = 0.030]. One group showed a trend [70-gene signature: HR (95% CI): 0.25 (0.00-1.02), P = 0.054].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. Clin Cancer Res; 23(21); 6505-15. ©2017 AACR.
Highlights
The past decades have shown a continuous trend to individualization of the selection of chemotherapy
After inverse probability weighting (IPW)-adjustment for patient and tumor characteristics, patients with high contralateral parenchymal enhancement (CPE) had significantly better overall survival than those with low CPE in groups at high risk according to the Nottingham Prognostic Index [hazard ratios (HR): 0.08 (0.00–0.40), P < 0.001]; Dutch clinical guidelines [HR: 0.22 (0.00–0.81), P 1⁄4 0.021]; and 21-gene recurrence score [HR: 0.14 (0.00–0.84), P 1⁄4 0.030]
In patients at high risk based on the tumor, subgroups at relatively low risk were identified using pretreatment enhancement of the stroma on breast dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI)
Summary
The past decades have shown a continuous trend to individualization of the selection of chemotherapy. Markers such as patient age, tumor size, tumor receptor status, and nodal involvement are used to select chemotherapy using prognostic models such as the Nottingham Prognostic Index and Adjuvant! Variation still exists in treatment outcome in patients who have similar markers. Note: Supplementary data for this article are available at Clinical Cancer Research Online (http://clincancerres.aacrjournals.org/). Overtreatment of breast cancer remains a concern in subgroups of patients, leading to adverse side effects such as chronic fatigue without survival benefit. Undertreatment may lead to recurrence and increased risk of succumbing to breast cancer. Patient-specific treatment of breast cancer is desired
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