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Developing a test to look for hundreds of cancer DNA mutations in a single blood sample, to guide treatment

Scientific Officers:Matthew Beany & Isaac Garcia Murillas. Final spend £149,411. 2018-2022

Project Summary

Some breast cancer patients will be cured by surgery alone, while others will relapse even with intensive
chemotherapy. Differences in the genetic mutations within genes and cancers mean that each patient will respond to it differently. Despite this, all can expect to receive the same chemotherapy dosage as others after surgery. For many, the chemotherapy may be more aggressive than necessary, causing avoidable and potentially harmful side effects.

Cancers, especially in the early stages, release only a very small amount of ctDNA into the blood. Liquid
biopsies are not yet considered sensitive enough to reliably pick up very low levels of ctDNA. On that basis, clinicians have not risked withdrawing chemotherapy from their patients after surgery, even though some may not require it.

In this project, 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.

Isaac Garcia Murillas took over the project from Matthew Beany mid 2021 and fine tuned the extra-sensitive tests using genomics data from early-stage breast cancer patients. The tests are now ready to be used to direct treatment plans.

Some patients diagnosed with breast cancer are cured by surgery alone. However, many also need chemotherapy to improve their chances of being cured. Working closely with other similar projects, including Grant 6 and Grant 3, this project aims to identify which patients would benefit from chemotherapy, much more accurately than we can currently. It also aims to identify who is still at risk of relapse despite receiving chemotherapy, so we can tailor their treatment accordingly. 


Matthew has developed extra-sensitive tests for cancer DNA mutations in blood, by developing patient specific panels that will look for more mutations in a single test than was previously achievable.

Current tests which look for traces of cancer in the blood are not sensitive enough to consider withdrawing potentially lifesaving chemotherapy from patients who have actually been cured by surgery alone. Access to the lab was restricted during the first COVID-19 pandemic lockdown, but Matthew has now started to validate approaches that can dramatically improve our ability to detect very low levels of cancer in the body, including estrogen receptor positive breast cancers known to release very low levels of tumour DNA into the blood stream. Ultimately, the aim is to develop a new test that is robust and accurate enough to be used to direct treatment plans. The team are hopeful that the new test will allow some women to avoid unnecessary chemotherapy and help to ensure women with breast cancer can receive more personalised and kinder treatment with better outcomes. 


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