title: Dense breast tissue in postmenopausal women is associated with a pro-inflammatory microenvironmentin vivo.
abstract: Inflammation is one of the hallmarks of carcinogenesis. High mammographic density has been associated with increased risk of breast cancer but the mechanisms behind are poorly understood. We evaluated whether breasts with different mammographic densities exhibited differences in the inflammatory microenvironment. Postmenopausal women attending the mammography-screening program were assessed having extreme dense, n = 20, or entirely fatty breasts (nondense), n = 19, on their regular mammograms. Thereafter, the women were invited for magnetic resonance imaging (MRI), microdialysis for the collection of extracellular moleculesin situand a core tissue biopsy for research purposes. On the MRI, lean tissue fraction (LTF) was calculated for a continuous measurement of breast density. LTF confirmed the selection from the mammograms and gave a continuous measurement of breast density. Microdialysis revealed significantly increased extracellularin vivolevels of IL-6, IL-8, vascular endothelial growth factor, and CCL5 in dense breast tissue as compared with nondense breasts. Moreover, the ratio IL-1Ra/IL-1β was decreased in dense breasts. No differences were found in levels of IL-1β, IL-1Ra, CCL2, leptin, adiponectin, or leptin:adiponectin ratio between the two breast tissue types. Significant positive correlations between LTF and the pro-inflammatory cytokines as well as between the cytokines were detected. Stainings of the core biopsies exhibited increased levels of immune cells in dense breast tissue. Our data show that dense breast tissue in postmenopausal women is associated with a pro-inflammatory microenvironment and, if confirmed in a larger cohort, suggests novel targets for prevention therapies for women with dense breast tissue.
authors.affiliation: Department of Oncology and Department of Clinical and Experimental Medicine, Linköping University , Linköping, Sweden.
authors.forename: Annelie
authors.initials: A
authors.lastname: Abrahamsson
authors.affiliation: Department of Radiology and Department of Medical and Health Sciences, Linköping University , Linköping, Sweden.
authors.forename: Anna
authors.initials: A
authors.lastname: Rzepecka
authors.affiliation: Department of Biomedical Engineering and Center for Medical Image Science and Visualization (CMIV), Linköping University , Linköping, Sweden.
authors.forename: Thobias
authors.initials: T
authors.lastname: Romu
authors.affiliation: Department of Biomedical Engineering and Center for Medical Image Science and Visualization (CMIV), Linköping University , Linköping, Sweden.
authors.forename: Magnus
authors.initials: M
authors.lastname: Borga
authors.affiliation: Department of Medical and Health Sciences, and Center for Medical Image Science and Visualization (CMIV), Linköping University , Linköping, Sweden.
authors.forename: Olof Dahlqvist
authors.initials: OD
authors.lastname: Leinhard
authors.affiliation: Department of Medical and Health Sciences, and Center for Medical Image Science and Visualization (CMIV), Linköping University , Linköping, Sweden.
authors.forename: Peter
authors.initials: P
authors.lastname: Lundberg
authors.affiliation: Department of Radiology and Department of Medical and Health Sciences and Center for Medical Image Science and Visualization, Linköping University , Linköping, Sweden.
authors.forename: Johan
authors.initials: J
authors.lastname: Kihlberg
authors.affiliation: Department of Oncology and Department of Clinical and Experimental Medicine, Linköping University , Linköping, Sweden.
authors.forename: Charlotta
authors.initials: C
authors.lastname: Dabrosin
keywords: Cytokines; MRI; mammary gland; mammography; microdialysis