Development of novel imaging biomarkers of tumour metabolism

Breast cancer is the most common cancer in women and can frequently be treated successfully. To select the most effective treatment, patients with breast cancer need to be grouped, or stratified, according to their precise tumour type. The tumour type is usually determined by microscopic assessment of tissue samples obtained during biopsy. However, it is known that the primary breast cancer and its metastases may contain groups of cells that display very different properties in microscopic appearance, DNA-alterations, and metabolism. The term tumour heterogeneity is used to describe this and this heterogeneity may necessitate different treatment strategies for successful response to drug therapy. The common clinical practice of obtaining a tumour biopsy from a single location often does not fully depict this heterogeneity and advanced imaging methods may come into play here. Another issue is that after a treatment is decided upon for an individual patient, it is desirable to evaluate response as early as possible, to allow rapid changes to the treatment if it is not effective reducing the side effects to the patient, increasing their chances of responding successfully and decreasing the use of ineffective drugs for the healthcare system. Standard methods for the imaging of breast cancer patients cannot fully assess tumour heterogeneity and this is especially true for bone metastases. Hyperpolarised MRI (HP MRI) is a new technique for studying tumour metabolism which greatly increases the signal that can be obtained with MRI. The metabolism of cancer cells is different from normal cells in that cancer cells use more glucose. With HP MRI, we can detect this difference in a way which has not been possible before and it may allow metabolic heterogeneity to be detected. This new imaging method is only starting to enter clinical research, but the first results are very promising. In this study, radiation free HP MRI will be combined with radionuclide imaging (18F-sodium fluoride positron emission tomography; 18F- NaF-PET), to optimize the diagnosis of bone metastases and the response to treatment. Another new technique for the detection of tumours is the measurement of small DNA fragments of cancer cells (circulating tumour DNA, ctDNA) that can be found in the blood of cancer patients. The amount of ctDNA decreases when the tumour shrinks. ctDNA may show a more complete picture of the DNA changes in the patients tumour than the tumour tissue obtained during a single biopsy. Some of these DNA changes allow targeted individualised therapy for the patient. This study will assess the combination of HP MRI, 18F-NaF-PET, and ctDNA for the comprehensive assessment of different properties of breast cancer in individual patients with the ultimate goal of improving the choice of treatment for both the primary tumour and metastases.