Funds raised by Le Cure support innovative breast cancer research projects at The Royal Marsden.
These pioneering research projects aim to transform and save the lives of breast cancer patients, providing them with better treatment options. Since its inception in 2014 Le Cure has created seven Le Cure Research Fellowships, five of which have been completed and have successfully developed the understanding of why breast cancers respond to treatment in different ways. In March 2021 the Le Cure Scientific Committee approved a grant for TRAK-ER which will be the focus of Le Cure fundraising until 2027.
We will be climbing the mountains again in 2023 to fund this ambitious and vital research.
Liquid biopsies can detect signs of relapse through circulating tumour (ctDNA) analysis nearly 11 months before it shows up in scans. The TRAK-ER team led by Professor Nick Turner hope that if relapse is detected early enough, patients may be able to receive treatment before extra mutations emerge that make it more difficult to treat. This would effectively mean that the relapse is treated before it becomes visible in scans, revolutionising treatment.
A sub-study will investigate oligo-metastatic disease, which is when molecular signs of relapse are detected in a limited number of locations away from the primary tumour site. Those identified as having oligo-metastatic disease will receive either the standard hormone therapy or the combination of palbociclib and fulvestrant.
The trial will also establish clinical data for the potential reduced use of chemotherapy in early breast cancers. The team will monitor those patients that did not have ctDNA detected at diagnosis to see whether, in the future, this group may be able to limit or avoid their exposure to chemotherapy.
Developing an individualised approach to chemotherapy will help to minimise the associated risk of toxic and debilitating side effects.
Extra-sensitive liquid biopsy tests have been developed that can look for more mutations in a single test than was previously possible. These tests can be used to identify patients who can safely limit their exposure to chemotherapy after surgery. These extra sensitive liquid biopsies can also be used to identify those who remain at risk of relapse despite receiving chemotherapy, so that their treatment can be tailored accordingly.
This trial distinguished patients with different risks of relapse by starting them on endocrine therapy two weeks before surgery and looking at how the levels of the Ki67protein changed in their tumours over time. It analysed each group to find differences in how its cancers behaved. Several immune cell types were found to be unusually active in ER positive cancers that contained progesterone. Further research will establish whether this is linked to resistance to endocrine therapy. If confirmed, targeted drugs are already available.
This trial recruited 208 patients from 17 sites from all over the UK. Of these, 195 patients had tissue sequenced for the presence of genetic mutations linked to relapse. Around 80% were found to have mutations in their cancer that could be monitored using liquid biopsies. Out of these, ctDNA was detected in 45 patients, indicating early signs of relapse. The trial hoped to test the patients on pembrolizumab to prevent relapse, but unfortunately discovered that relapse had already occurred in the majority of those patients.
Dr Charlotte Fribbens found that estrogen receptor mutations could be detected over six months before the relapse shows up in scans, which opened up the possibility to treat relapse at a molecular level. In doing so the trial demonstrated for the first time that liquid biopsies can inform and guide personalised treatment for patients.
Looking at the group of patients who do not respond to hormonal treatment Dr Mariana Ferreira Leal demonstrated that it is possible to deliver accurate molecular analysis within a week of a patient starting treatment. This was a prerequisite to launch the much larger POETIC2 study. Her research then identified patients whose cancer cells were resistant to the Aromatase Inhibitors (AIs) that are used to treat hormone receptor positive breast cancers with the aim of guiding more optimal treatment choices.
This study by Claire Swift & Monee Shamsher used the Illumina MiniSeq machine to establish the data necessary to develop the extra-sensitive liquid biopsy tests within Grant 4. This data supported the use of liquid biopsies to detect relapse and identify patients who do not need chemotherapy.
Information about the research has been extracted from The Le Cure Fund Update published in Spring 2022 prepared by Professor Ian Smith, Chair of the Le Cure Scientific Committee, Professor Nick Turner, Head of the Ralph Lauren Centre for Breast Cancer Research, Professor Mitch Dowsett, Claire Swift and others. If you have any questions or would like more information please contact Freya Demmery at the Royal Marsden Cancer Charity: [email protected]