Image: Pipette tips used during an experiment.
An innovative trial to detect relapse in breast cancer patients with circulating tumour DNA (ctDNA) has opened at The Royal Marsden NHS Foundation Trust.
The first patients with oestrogen receptor (ER) positive breast cancer have been recruited to the TRAK-ER trial and will have a blood test every three months, for up to three years, to detect their risk of cancer returning. If risk of relapse is indicated, their treatment will be altered to try and prevent relapse from happening.
The TRAK-ER trial, led by researchers at The Royal Marsden and The Institute of Cancer Research, London, will establish a circulating tumour DNA (ctDNA) surveillance programme for over 1,000 patiets with ER positive breast cancer who are currently receiving hormone therapy to reduce their risk of cancer returning. The trial will be rolled out to 20 UK centres over the next six months.
Detecting tiny levels of tumour DNA in blood
Cancer cells release DNA into the bloodstream known as circulating tumour DNA (ctDNA). The blood tests used in the trial can detect very low levels of ctDNA in a blood sample, to help determine whether any cancer is present in the body.
Very low levels of cancer found in the blood is known as molecular relapse, which indicates that the patient will eventually relapse. Therefore, testing a patient’s blood for ctDNA will allow clinicians to diagnose the return of cancer at the very earliest stage. Previous studies have shown that ctDNA blood tests can identify relapse several months or even years before it can be seen on a scan.
A blood sample and tumour material from each patient’s previous breast cancer surgery will be analysed to design a personalised ctDNA test for each individual on the trial. Following a blood test, if cancer is detected in a patient’s blood, but there is no evidence of cancer on scan, they will be randomly allocated one of two treatment options.
Potential to revolutionise treatment
One group will receive both palbociclib (IbranceTM) and fulvestrant (FaslodexTM), whilst the other group will be offered either a change in their standard hormone therapy or they will continue on the same hormone therapy they are currently taking. The trial will look to see if patients treated with palbociclib and fulvestrant are less likely to relapse compared to those receiving standard hormone therapies.
Principal investigator of the TRAK-ER trial, Professor Nicholas Turner, Professor of Molecular Oncology at the ICR, and Consultant Medical Oncologist at The Royal Marsden, said:
“The risk of relapse for ER positive breast cancer patients is spread out over many years after initial treatment, which is one of the reasons why scans aren't effective in trying to pick it up. Blood tests could become the standard way of following up with this group of patients, and if the trial produces encouraging results, this could revolutionise how we treat ER positive breast cancer patients in the future and hopefully save more lives.”
'Extremely lucky to be part of this trial'
Elaine Nangle, 41, from Reading, was diagnosed with stage three lobular breast cancer in March 2020. Following treatment which included chemotherapy, radiotherapy and a mastectomy, she received the news that she was cancer free and was given the opportunity to join the TRAK-ER trial at The Royal Marsden.
She said: “Being part of something that may be able to give me forewarning of relapse is incredible and just knowing that I’m being monitored so frequently gives me a huge safety net. When you finish cancer treatment, it’s normal to feel like your safety net has been withdrawn, so I feel extremely lucky to be part of this trial. Anything that gives me a greater chance of being here for longer, and being well for longer, is amazing.”
Robert Nussbaum, M.D., chief medical officer at Invitae, said:
“Using a highly sensitive, personalised liquid biopsy to detect nascent cancer recurrence enables escalated intervention when it can be most effective, or even curative, for patients. This study will lay the groundwork for better post-treatment monitoring and potentially life-extending treatment for patients with ER-positive breast cancer.”
The trial is an independent research study led by The Royal Marsden and funded by Pfizer, Invitae and Le Cure.