TRAK-ER

Led by Professor Nick Turner, Head of the Ralph Lauren Centre for Breast Cancer Research. Budgeted cost £2.1 million. Project length: 2021-2027

In November 2020, Professor Nick Turner presented the Le Cure Scientific Committee with an opportunity to support key translational research, alongside a major international trial which aims to accelerate the use of ctDNA analysis into routine clinical use in breast cancer care. Researchers can use a blood test or liquid biopsy to detect tiny amounts of tumour DNA. This may indicate a higher risk of relapse. The Scientific Committee have approved funding to support this exciting new project.

Project Summary

Patients with Estrogen Receptor (ER) positive breast cancer, make up around 70% of all breast cancer cases. Despite current treatments, patients with ER positive breast cancer are at risk of relapse over at least the first two decades, after initial diagnosis. Beyond classic prognostic factors, there are currently no tests being used in clinical practice that can identify which individual patients are at highest risk of relapse, particularly in later relapse. 

Professor Turner’s team have previously trialed the use of ctDNA analysis to detect relapse earlier. Results demonstrated that relapse could be detected nearly 11 months before clinical diagnosis. Professor Turner is now hoping to accelerate the use of ctDNA analysis into routine clinical practice for early stage breast cancer, identifying those who are at high risk of relapse and enabling further therapy to be given much sooner. After a year of planning and designing TRAK-ER opened for recruitment in March 2022. The team hope to recruit 1,100 women for surveillance, in the UK and France. Blood samples will be collected for ctDNA analysis for three years and will be used to identify patients with a positive ctDNA result and therefore at high risk of relapse. Professor Turner will then test whether these patients are treated more successfully on standard endocrine therapy or on a combination of Palbociclib, a targeted inhibitor therapy and the hormone therapy drug Fulvestrant. 

Le Cure’s funding for this work will also help Professor Turner develop evidence for a new approach to managing patients with oligo-metastatic disease, when slight relapse is detected, but in a limited number of locations away from the primary tumour site. Like the main trial, patients who are identified as having oligo-metastatic disease will either receive endocrine therapy or the combination of Palbociclib and Fulvestrant to determine the best treatment option. 

Le Cure has also funded two vital pieces of equipment to help with the trial. QIAsymphony is a robot that can extract DNA from 96 patient samples at once, whilst Zephyr G3 can automate sequencing of the samples. This will help the team process the samples much more quickly, saving time and eliminating the potential for human error.

Professor Turner also hopes to provide data for the de-escalation of chemotherapy in early breast cancers, to prevent patients from receiving this treatment unnecessarily. His team will monitor patients from whom ctDNA is not detected at diagnosis to determine whether there is evidence to suggest these patients can avoid chemotherapy altogether. 

This work has the potential to transform the lives of patients with ER positive breast cancer by detecting relapse sooner, when more treatment options are available, while identifying patients who do not need further therapy will enable them to move on with their lives beyond cancer.