Peter Lundberg1,2, Mikael F Forsgren2,3,4, Jens Tellman1,2, Johan Kihlberg2,4, Anna Rzepecka4, Charlotta Dabrosin5. 1. Department of Radiation Physics and Department of Medical and Health Sciences, Linköping University, Linköping, Sweden. 2. Center for Medical Image Science and Visualization (CMIV), Linköping University, Linköping, Sweden. 3. AMRA Medical AB, Linköping, Sweden. 4. Department of Radiology and Department of Medical and Health Sciences, Linköping University, Linköping, Sweden. 5. Department of Oncology and Department of Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden. charlotta.dabrosin@liu.se.
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.
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.
Authors: Norman F Boyd; Lisa J Martin; Michael Bronskill; Martin J Yaffe; Neb Duric; Salomon Minkin Journal: J Natl Cancer Inst Date: 2010-07-08 Impact factor: 13.506
Authors: Suling J Lin; Jennifer Cawson; Prue Hill; Izhak Haviv; Mark Jenkins; John L Hopper; Melissa C Southey; Ian G Campbell; Erik W Thompson Journal: Breast Cancer Res Treat Date: 2011-01-22 Impact factor: 4.872
Authors: Karthik Ghosh; Kathleen R Brandt; Carol Reynolds; Christopher G Scott; V S Pankratz; Darren L Riehle; Wilma L Lingle; Tonye Odogwu; Derek C Radisky; Daniel W Visscher; James N Ingle; Lynn C Hartmann; Celine M Vachon Journal: Breast Cancer Res Treat Date: 2011-08-30 Impact factor: 4.872
Authors: Diana S M Buist; Peggy L Porter; Constance Lehman; Stephen H Taplin; Emily White Journal: J Natl Cancer Inst Date: 2004-10-06 Impact factor: 13.506
Authors: Debra Hawes; Susan Downey; Celeste Leigh Pearce; Sue Bartow; Peggy Wan; Malcolm C Pike; Anna H Wu Journal: Breast Cancer Res Date: 2006-04-28 Impact factor: 6.466
Authors: Jia-Min B Pang; David J Byrne; Elena A Takano; Nicholas Jene; Lara Petelin; Joanne McKinley; Catherine Poliness; Christobel Saunders; Donna Taylor; Gillian Mitchell; Stephen B Fox Journal: PLoS One Date: 2015-06-25 Impact factor: 3.240
Authors: Qamar J Khan; Bruce F Kimler; Anne P O'Dea; Carola M Zalles; Priyanka Sharma; Carol J Fabian Journal: Breast Cancer Res Date: 2007 Impact factor: 6.466
Authors: Salem Alowami; Sandra Troup; Sahar Al-Haddad; Iain Kirkpatrick; Peter H Watson Journal: Breast Cancer Res Date: 2003-07-23 Impact factor: 6.466