Wellcome Trust PhD Programme for Clinicians at the University of Cambridge. (360G-Wellcome-106566_Z_14_Z)

Circulating cell free tumour DNA (ctDNA) concentrations correlate very closely with cancer burden. Current techniques can reliably detect ctDNA at frequencies above 2% (as occurs in metastatic disease) however the identification of ctDNA in early malignancy remains a challenge. It is my aim to develop technologies to detect ctDNA at very low allelic frequencies, using a cohort of patients with active early stage breast cancer receiving chemotherapy. Following the identification of tumour mutations by exome sequencing, I will track these mutations within the plasma using microfluidic technologies and targeted sequencing. Concurrently, I will design and initiate a pilot trial to gather serial blood samples from patients with early stage breast cancer who are being treated radically, in order to investigate whether ctDNA is detectable before clinically confirmed disease recurrence. If this is the case, then trials could be designed to determine whether ctDNA can be used as a screening tool for relapse. Finally, using tumour and plasma sequencing, I aim to characterise how a previously treatment naiive tumour evolves when subjected to chemotherapy. Using probabilistic models, this could allow us to predict response to treatment given a certain molecular signature.