Topographic enhancement mapping of the cancer-associated breast stroma using breast MRI

Abstract

In animal and laboratory models, cancer-associated stroma, or elements of the supporting tissue surrounding a primary tumor, has been shown to be necessary for tumor evolution and progression. However, little is understood or studied regarding the properties of intact stroma in human cancer in vivo. In addition, for breast cancer patients, the optimal volume of local tissue to treat surrounding a primary tumor is not clear. Here, we performed an interdisciplinary study of normal-appearing breast tissue using breast magnetic resonance imaging (MRI), correlative histology and array comparative genomic hybridization to identify a cancer-associated stroma in humans. Using a novel technique for segmenting breast fibroglandular tissue, quantifiable topographic percent enhancement mapping of the stroma surrounding invasive breast cancer was found to be significantly elevated within 2 cm of the tumor edge. This region was also found to harbor increased microvessel density, and genomic changes that were closely associated with host normal breast tissue. These findings indicate that a cancer-associated stroma may be identified and characterized in human breast cancer using non-invasive imaging techniques. Identification of a cancer-associated stroma may be further developed to help guide local therapy to reduce recurrence and morbidity in breast cancer patients.

Modelling Vascularity in Breast Cancer and Surrounding Stroma Using Diffusion MRI and Intravoxel Incoherent Motion

“…The monoexponential ADC showed little variation with distance from the tumor, in agreement with [6]. The pseudodiffusion fraction, f p , decreased with distance from the tumor (Figure 3b), consistent with lower microvessel density [3] and previous DCE data [2]. These IVIM parameters suggest that the smaller contribution of vascular perfusion to the signal further from the tumor is compensated for by freer diffusion in the extravascular space, resulting in a similar calculated ADC value throughout the stroma when a two-point ADC method is used.…”

“…Furthermore, there was no significant difference between ADC in stroma near (2-5 mm) and far (9-13 mm) from the tumor. This is somehwat puzzling since microvessel density decreases with distance from the tumor [3] and the protein content and density of the extracellular matrix also vary. This may be because ADC lacks specificity to microstructural changes: a decrease in vascular pseudodiffusion can be compensated for by faster diffusion in the extravascular space.…”

“…For example, signal enhancement from Dynamic ContrastEnhanced Magnetic Resonance Imaging (DCE-MRI) correlates with tumor recurrence [1] and survival [2]. There is also spatial variation: signal enhancement ratio becomes less prominent with distance from the tumor, an effect that correlates with microvessel density [3]. However, DCE-MRI signal at low temporal resolution depends on many physiological parameters, including the microvessel density, blood flow, vessel permeability and the extracellular space into which contrast agent leaks.…”

Association between Parenchymal Enhancement of the Contralateral Breast in Dynamic Contrast-enhanced MR Imaging and Outcome of Patients with Unilateral Invasive Breast Cancer

“…Relatively high signal enhancement ratio values around the tumor have been associated with more ipsilateral recurrence in patients with ductal carcinoma in situ (7). Increase in near-tumor signal enhancement ratio has also been associated with increased microvessel density (27). To our knowledge, association between BREAST IMAGING: Parenchymal Enhancement of Contralateral Breast in Invasive Breast Cancer van der Velden et al has not yet been reported.…”

Spatially Resolved Metabolic Phenotyping of Breast Cancer by Desorption Electrospray Ionization Mass Spectrometry

“…There is growing evidence that peritumoral microenvironmental changes may represent underlying mechanisms that affect tumor cell initiation, progression, and disease prognosis (11) and may affect surgical margins and risk of recurrence. Dynamic contrast enhanced magnetic resonance imaging has been used to identify this tumor-associated stroma (12).…”