Research Scientist: Claire Swift. Spend: £65,580. 2018 – 2022.
The c-TRAK TN trial took place at the Ralph Lauren Centre for Breast Cancer Research at The Royal Marsden. The trial recruited patients with moderate or high-risk triple negative breast cancer, a subtype of breast cancer that does not respond to hormone blocking drugs and is often more aggressive than most other subtypes. Eligible patients had their cancer screened for the presence of gene mutations and once they had completed their standard treatment, they had blood tests taken every 3 months to monitor for ctDNA. Eligible patients were offered the immunotherapy drug pembrolizumab, which works by stimulating the body’s own immune system to recognise and mount a response against cancer cells.
The purpose of the c-TRAK TN trial was two-fold.
(1) To assess if a blood test can predict which patients are at highest risk of relapse by detecting tiny amounts of cancer that remain in the body, that are not visible through imaging.
(2) To assess the potential effectiveness of further therapy with the new drug Pembrolizumab, an immunotherapy drug which stimulates the body’s immune response to fight cancer cells.
The trial recruited 208 patients from 17 sites from all over the UK. Of these, 195 patients had tissue samples from their breast cancers sequenced for the presence of genetic mutations linked to relapse.
over the UK. Around 80% (161 patients) were found to have mutation(s) in their cancer that could be monitored using liquid biopsies. Out of these, ctDNA was detected in 45 patients, indicating early signs of relapse.Patients with a positive ctDNA result moved into the next phase of the trial, which tested the immunotherapy drug pembrolizumab: 31 were allocated to receive pembrolizumab and the rest were to continue on standard treatment. Unfortunately, the team were not able to confidently show that the immunotherapy helps. By the time the patients were supposed to start taking pembrolizumab, scans revealed three quarters had already relapsed, making them ineligible to receive it. This points to the aggressive nature of triple negative breast cancer and suggests that the liquid biopsy tests were not conducted regularly enough in the trial. Only three patients ended up receiving pembrolizumab, with
one seeing their ctDNA reduce as a result.
While these results may not have been what the team had hoped for, they will help future studies to be
designed more effectively. Since most patients had already relapsed between their three-monthly blood
tests, and the cancer spread very quickly, the findings emphasise the importance of commencing ctDNA testing early and testing more frequently. The findings also unveiled previously unappreciated molecular differences in the behaviour of triple negative breast cancer, notably the extensive genomic diversity of these cancers and their highly diverse ctDNA trajectories. This information can be used to advance future research into why these tumours mutate quickly and become resistant, which may be key to improving treatments for triple negative breast cancers. Preliminary data from the study was presented by Professor Turner at the San Antonio Breast Cancer Symposium in December 2021 and the manuscript will soon be submitted for publication in a peer reviewed journal.