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Breast density is strongly associated with multiparametric magnetic resonance imaging biomarkers and pro-tumorigenic proteins in situ

British Journal of Cancer, 2022

Lundberg P., Forsgren M., Tellman J., Kihlberg J., Rzepecka A., Dabrosin C.

Disease areaApplication areaSample typeProducts
Oncology
Pathophysiology
Microdialysis Fluid
Olink Target 96

Olink Target 96

Abstract

Background

High mammographic density is an independent risk factor for breast cancer by poorly understood molecular mechanisms. Women with dense breasts often undergo conventional magnetic resonance imaging (MRI) despite its limited specificity, which may be increased by diffusion-weighted imaging (DWI) with apparent diffusion coefficient (ADC) and contrast. How these modalities are affected by breast density per se and their association with the local microenvironment are undetermined.

Methods

Healthy postmenopausal women attending mammography screen with extremely dense or entirely fatty breasts underwent multiparametric MRI for analyses of lean tissue fraction (LTF), ADC and perfusion dynamics. Microdialysis was used for extracellular proteomics in situ.

Results

Significantly increased LTF and ADC and delayed perfusion were detected in dense breasts. In total, 270 proteins were quantified, whereof 124 related to inflammation, angiogenesis, and cellular growth were significantly upregulated in dense breasts. Most of these correlated significantly with LTF, ADC and the perfusion data.

Conclusions

ADC and perfusion characteristics depend on breast density, which should be considered during the implementation of thresholds for malignant lesions. Dense and nondense breasts are two essentially different biological entities, with a pro-tumorigenic microenvironment in dense breasts. Our data reveal several novel pathways that may be explored for breast cancer prevention strategies.

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