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Oncology Abstracts (2019) 1 P028 | DOI: 10.1530/oncolabs.1.P028

1Discipline of Surgery, School of Medicine, The Queen Elizabeth Hospital, University of Adelaide, Woodville, Australia; 2The Robinson Research Institute, University of Adelaide, Adelaide, Australia; 3Discipline of Obstetrics and Gynaecology, School of Medicine, University of Adelaide, Adelaide, Australia; 4The University of Melbourne Department of Surgery, St Vincent’s Hospital Melbourne, Melbourne, Australia; 5Metastasis Research Laboratory, Peter MacCallum Cancer Centre, Melbourne, Australia; 6The Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, Australia; 7Institute of Health and Biomedical Innovation, School of Biomedical Sciences, Queensland University of Technology and Translational Research Institute, Queensland, Australia; 8School of Veterinary Sciences, University of Adelaide, Roseworthy, SA, Australia; 9MRC and University of Edinburgh Centre for Reproductive Health, Queen’s Medical Research Institute, University of Edinburgh, Edinburgh, UK.

High breast density is an independent risk factor for breast cancer. There is exciting potential for breast density to become a widespread health assessment tool, used to identify the women most at risk of breast cancer in order to intervene early and reduce that risk. However, a better understanding of causal biological mechanisms that lead to high breast density is required in order to develop therapeutic approaches. This project aimed to identify and investigate biological drivers of breast density. We have developed a grounding-breaking new approach to study breast density. Fresh breast tissue from surgical samples are cut into 1 cm slices and x-rayed. The x-ray image guides biopsies of high and low density regions from the same individual. The cellular and molecular components of these tissues are assessed under the microscope and statistically analysed as paired samples. This enables us to overcome the problem of heterogeneity within the breast, and the high variability between individuals. Using this approach, we demonstrated that regions of high density contained increased abundance of epithelial and stromal cells compared to regions of low density. Density was not associated with changes in hormone receptors or epithelial cell proliferation. Most striking however were differences in immune cells and immune signalling factors between paired samples. High density was associated with increased abundance of macrophages and pro-inflammatory protein C-C Motif Chemokine Ligand 2 (CCL2). To investigate whether immune signalling is a driver of high breast density, we engineered a genetically modified mouse model whereby the mammary gland specific MMTV promoter drives constitutive CCL2 expression. These studies revealed that CCL2-driven inflammation led to increased density and increased susceptibility to mammary cancer. This is the first study to demonstrate a causal role for immune system signalling in breast density and opens the door for new approaches to reducing breast cancer risk using anti-inflammatory drugs in women with dense breasts.

Volume 1

7th International Pacific Rim (PacRim) Breast and Prostate Cancer Meeting

17 Mar 2019 - 20 Mar 2019

PacRim Breast and Prostate Cancer Group 

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