title: Mammographically dense human breast tissue stimulates MCF10DCIS.com progression to invasive lesions and metastasis.
abstract: High mammographic density (HMD) not only confers a significantly increased risk of breast cancer (BC) but also is associated with BCs of more advanced stages. However, it is unclear whether BC progression and metastasis are stimulated by HMD. We investigated whether patient-derived HMD breast tissue could stimulate the progression of MCF10DCIS.com cells compared with patient-matched low mammographic density (LMD) tissue.
  
  
  
  Sterile breast specimens were obtained immediately after prophylactic mastectomy from high-risk women (n = 10). HMD and LMD regions of each specimen were resected under radiological guidance. Human MCF10DCIS.com cells, a model of ductal carcinoma in situ (DCIS), were implanted into silicone biochambers in the groins of severe combined immunodeficiency mice, either alone or with matched LMD or HMD tissue (1:1), and maintained for 6 weeks. We assessed biochamber weight as a measure of primary tumour growth, histological grade of the biochamber material, circulating tumour cells and metastatic burden by luciferase and histology. All statistical tests were two-sided.
  
  
  
  HMD breast tissue led to increased primary tumour take, increased biochamber weight and increased proportions of high-grade DCIS and grade 3 invasive BCs compared with LMD. This correlated with an increased metastatic burden in the mice co-implanted with HMD tissue.
  
  
  
  Our study is the first to explore the direct effect of HMD and LMD human breast tissue on the progression and dissemination of BC cells in vivo. The results suggest that HMD status should be a consideration in decision-making for management of patients with DCIS lesions.
authors: Department of Surgery, University of Melbourne, St Vincent's Hospital, Melbourne, VIC, 3156, Australia.
authors: Cecilia W
authors: CW
authors: Huo
authors: Department of Surgery, University of Melbourne, St Vincent's Hospital, Melbourne, VIC, 3156, Australia.|St Vincent's Institute of Medical Research, Melbourne, VIC, 3156, Australia.
authors: Mark
authors: M
authors: Waltham
authors: Department of Pathology, Peter MacCallum Cancer Centre, 305 Grattan St, Melbourne, VIC, 3000, Australia.
authors: Christine
authors: C
authors: Khoo
authors: Department of Pathology, Peter MacCallum Cancer Centre, 305 Grattan St, Melbourne, VIC, 3000, Australia.|Department of Pathology, University of Melbourne, Grattan Street, Parkville, VIC, 3010, Australia.|Sir Peter MacCallum Department of Oncology, University of Melbourne, Grattan Street, Parkville, VIC, 3010, Australia.
authors: Stephen B
authors: SB
authors: Fox
authors: Department of Pathology, St Vincent's Hospital, Melbourne, VIC, 3156, Australia.
authors: Prue
authors: P
authors: Hill
authors: Department of Pathology, St Vincent's Hospital, Melbourne, VIC, 3156, Australia.
authors: Shou
authors: S
authors: Chen
authors: Department of Surgery, University of Melbourne, St Vincent's Hospital, Melbourne, VIC, 3156, Australia.|Austin Health and Northern Health, Melbourne, VIC, 3084, Australia.
authors: Grace L
authors: GL
authors: Chew
authors: College of Health and Biomedicine, Victoria University, St Albans, VIC, 8001, Australia.|Department of Biochemistry and Molecular Biology, School of Biomedical Sciences, Monash University, Clayton, VIC, 3800, Australia.|Australian Institute for Musculoskeletal Science (AIMSS), Victoria University, University of Melbourne and Western Health, Sunshine Hospital, St Albans, VIC, 3021, Australia.
authors: John T
authors: JT
authors: Price
authors: College of Health and Biomedicine, Victoria University, St Albans, VIC, 8001, Australia.
authors: Chau H
authors: CH
authors: Nguyen
authors: Institute of Health and Biomedical Innovation and School of Biomedical Sciences, Queensland University of Technology, 2 George Street, Brisbane, QLD, 4001, Australia.|Translational Research Institute, 37 Kent Street, Woolloongabba, QLD, 4102, Australia.|Australian Prostate Cancer Centre - Queensland, Brisbane, QLD, 4102, Australia.
authors: Elizabeth D
authors: ED
authors: Williams
authors: Department of Surgery, University of Melbourne, St Vincent's Hospital, Melbourne, VIC, 3156, Australia.|Division of Surgery, Peter MacCallum Cancer Centre, Melbourne, VIC, 3002, Australia.
authors: Michael
authors: M
authors: Henderson
authors: Department of Surgery, University of Melbourne, St Vincent's Hospital, Melbourne, VIC, 3156, Australia. e2.thompson@qut.edu.au.|St Vincent's Institute of Medical Research, Melbourne, VIC, 3156, Australia. e2.thompson@qut.edu.au.|Institute of Health and Biomedical Innovation and School of Biomedical Sciences, Queensland University of Technology, 2 George Street, Brisbane, QLD, 4001, Australia. e2.thompson@qut.edu.au.|Translational Research Institute, 37 Kent Street, Woolloongabba, QLD, 4102, Australia. e2.thompson@qut.edu.au.
authors: Erik W
authors: EW
authors: Thompson
authors: Sir Peter MacCallum Department of Oncology, University of Melbourne, Grattan Street, Parkville, VIC, 3010, Australia.|Department of Anatomy and Developmental Biology, Monash University, Melbourne, VIC, 3800, Australia.|Metastasis Research Laboratory, Peter MacCallum Cancer Centre, Melbourne, Victoria, 3000, Australia.
authors: Kara L
authors: KL
authors: Britt
mesh_terms: D000328:Adult; D000818:Animals; D014408:Biomarkers, Tumor; D000071060:Breast Density; D001943:Breast Neoplasms / Q000000981:diagnostic imaging* / Q000473:pathology* / Q000601:surgery; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D018450:Disease Progression; D005260:Female; D064593:Heterografts; D006801:Humans; D008327:Mammography / Q000379:methods; D051379:Mice; D008875:Middle Aged; D009154:Mutation; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D000072036:Prophylactic Mastectomy; D012307:Risk Factors
chemical_list: D014408:Biomarkers, Tumor
keywords: Breast cancer; MCF10DCIS.com; Mammographic density; Murine biochamber