Title: Is lipid composition mapping using magnetic resonance imaging an effective early detection tool for breast cancer in high risk populations?
Funder: Cancer Research UK

Abstract: Background: Breast cancer is a major and expanding societal challenge, despite significant improvement in survival rate. The current screening method has been shown to lead to overtreatment, prompting the development of accurate early detection approaches with clinical actionability. Genetic mutation carriers of BRCA1/2 and TP53 are at risk of breast cancer and receive annual surveillance in NHS. However, the current diagnostic approach relies on sensitivity to angiogenesis once malignancies are well under development, demanding early detection approaches sensitive to the tissue microenvironment changes during cancer initiation. Deregulation of lipid composition has been shown in BRCA1/2 mutation carriers. Polyunsaturated fatty acid is depleted in tumour initiation, while free fatty acids are released from surrounding mammary adipocytes. Within the tumour, production of saturated fatty acid is elevated, with subsequent conversion to monounsaturated fatty acid. Non-invasive quantification of lipid composition can be achieved using specialist magnetic resonance (MR) spectroscopy method, but limited to a single spatial location and is unable to probe the spatial variation of lipid composition during cancer initiation. Recently, chemical shift imaging (CSI), through the integration of MR spectroscopy and imaging approaches, was developed to provide lipid composition maps of the entire breast. Aims: The overarching aim is to improve early and accurate cancer detection in genetic mutation carriers at high risk of breast cancer through the assessment of whole breast lipid composition. This primer will establish the ability of CSI to detect whole breast lipid composition changes arising from cancer initiation, performance of CSI compared to current clinical imaging approach, agreement between CSI and MR spectroscopy, and reproducibility of CSI. Methods: We therefore propose a cross sectional study in 20 genetic mutation carriers at high risk of breast cancer and 20 patients with newly diagnosed breast cancer to undergo a single MR scan at Aberdeen Biomedical Imaging Centre, with imaging protocol comprising of MR spectroscopy, CSI, and conventional diagnostic MR imaging. The lipid composition of a single spatial location will be derived from MR spectroscopy, with corresponding maps from CSI. Aberdeen has proven track record in delivering advanced methods for breast imaging, supported by the close collaboration between scientists and clinicians. How the results of this research will be used: These results will provide a cornerstone for more substantive grant applications to establish CSI as a preferred approach for high risk population annual screening in a multi-centre study and the development of targeted lifestyle modification for breast cancer prevention.

Lay abstract: Background: Breast cancer is a major and expanding societal challenge, despite significant improvement in survival rate. The current screening method has been shown to lead to overtreatment, prompting the development of accurate early detection approaches with clinical actionability. Genetic mutation carriers of BRCA1/2 and TP53 are at risk of breast cancer and receive annual surveillance in NHS. However, the current diagnostic approach relies on sensitivity to angiogenesis once malignancies are well under development, demanding early detection approaches sensitive to the tissue microenvironment changes during cancer initiation. Deregulation of lipid composition has been shown in BRCA1/2 mutation carriers. Polyunsaturated fatty acid is depleted in tumour initiation, while free fatty acids are released from surrounding mammary adipocytes. Within the tumour, production of saturated fatty acid is elevated, with subsequent conversion to monounsaturated fatty acid. Non-invasive quantification of lipid composition can be achieved using specialist magnetic resonance (MR) spectroscopy method, but limited to a single spatial location and is unable to probe the spatial variation of lipid composition during cancer initiation. Recently, chemical shift imaging (CSI), through the integration of MR spectroscopy and imaging approaches, was developed to provide lipid composition maps of the entire breast. Aims: The overarching aim is to improve early and accurate cancer detection in genetic mutation carriers at high risk of breast cancer through the assessment of whole breast lipid composition. This primer will establish the ability of CSI to detect whole breast lipid composition changes arising from cancer initiation, performance of CSI compared to current clinical imaging approach, agreement between CSI and MR spectroscopy, and reproducibility of CSI. Methods: We therefore propose a cross sectional study in 20 genetic mutation carriers at high risk of breast cancer and 20 patients with newly diagnosed breast cancer to undergo a single MR scan at Aberdeen Biomedical Imaging Centre, with imaging protocol comprising of MR spectroscopy, CSI, and conventional diagnostic MR imaging. The lipid composition of a single spatial location will be derived from MR spectroscopy, with corresponding maps from CSI. Aberdeen has proven track record in delivering advanced methods for breast imaging, supported by the close collaboration between scientists and clinicians. How the results of this research will be used: These results will provide a cornerstone for more substantive grant applications to establish CSI as a preferred approach for high risk population annual screening in a multi-centre study and the development of targeted lifestyle modification for breast cancer prevention.

Research activity codes: 4.1 DISCOVERY AND PRECLINICAL TESTING OF MARKERS AND TECHNOLOGIES;4.2 EVALUATION OF MARKERS AND TECHNOLOGIES
Health categories: CANCER AND NEOPLASMS