A blood test that can identify a variety of mutations in advanced breast cancer can match women to effective targeted treatments, according to the early results of a major clinical trial.
The team at The Institute of Cancer Research, London, and The Royal Marsden NHS Foundation Trust say their blood test is now reliable enough to be offered to patients on the NHS once it has passed approval.
This has the potential to reshape care and speed up access to the best available drugs, they write in today’s (11 September 2020) edition of The Lancet Oncology.
Blood samples were analysed from more than 1,000 women with breast cancer that had recurred after treatment or had spread to another part of the body, to see if the test could improve treatment for those whose breast cancer is caused by a rarer mutation.
They detected mutations found in tumour DNA that had been shed into the bloodstream of women with advanced breast cancer and then they matched patients to targeted treatments.
The researchers looked at three targetable defects HER2, AKT1 and ESR1, which are known to drive breast cancer.
There were 142 women with these detectable mutations who were given experimental drugs targeted against the specific characteristics of their cancer: those with ESR1 mutations were treated with fulvestrant, while women with HER2 mutations received neratinib on its own or with fulvestrant.
Women with AKT1 mutations were split into two groups, depending on whether or not their cancer was oestrogen receptor positive or not. They were treated with capivasertib plus fulvestrant, or with capivasertib on its own.
Researchers found that some women with HER2 and AKT1 mutations responded to the treatments assigned to them.
Five out of 20 women with rare HER2 mutations who were prescribed neratinib saw a beneficial response, while four out of 18 patients with AKT1 mutations responded to capivasertib.
However, the researchers found that treatment targeting the ESR1 mutation was not effective.
The findings were validated by checking the patients’ tissue samples to confirm that the liquid biopsies had correctly identified the presence or absence of the mutations in more than 93% of cases.
The team hopes the findings will enable the adoption of liquid biopsies into clinical practice for patients with advanced cancer.
Study leader Professor Nick Turner, professor of molecular oncology at The Institute of Cancer Research, London, and Head of the Ralph Lauren Centre for Breast Cancer Research at The Royal Marsden, said: “Our findings show that simple blood tests can quickly and accurately tell us the genetic changes present in a patient’s cancer, and use that information to select the most suitable available treatment.
“Using a liquid biopsy could be particularly important for patients with advanced breast cancer, to help select the most appropriate treatment.
“Tests that detect tumour DNA in the blood have huge potential and could transform how doctors select targeted therapies for patients with advanced cancer.
“Our study shows that these liquid biopsies can pick up the mutations that drive a patient’s breast cancer and can successfully match patients with the best available precision medicine for their cancer.”
Study co-leader Professor Judith Bliss, professor of clinical trials at The Institute of Cancer Research, London, and director of its Cancer Research UK-funded Clinical Trials and Statistics Unit, added: “The plasmaMATCH trial platform has allowed us to look at the activity of various different treatments at the same time. This efficient trial set-up has been a success and it is already starting to bring patients closer to new targeted treatments.”
Lancet Oncology 11 September 2020
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