Liquid biopsy test found useful in breast cancer management

Emobileclinic Researchers Corner 



Researchers from the Institute of Cancer Research, London and the Royal Marsden NHS Foundation Trust have in a study published in the Journal of Clinical Oncology shown that liquid biopsy test can be used to detect low levels of Cancer DNA in the blood, identify women whose response to current hormonal treatment will be positive as well those with possibility of poor response.


The test detects mutations to a gene known as oestrogen receptor 1, or ESR1, which indicate that receptors for the female hormone oestrogen in the cancer cells that are usually driven by the hormone have evolved to stay permanently switched on without it – meaning hormonal treatments that block oestrogen production will no longer be effective.
Testing women for the ESR1 mutation allows patients to be separated into two groups, giving clinicians valuable information about which treatment is most likely to be effective.
The study used blood samples from a total of 783 women enrolled on two major phase III clinical trials of new treatments for advanced oestrogen receptor positive breast cancer, which accounts for three quarters of all cases. The thrust of the study was to ascertain the most effective treatments for breast cancers that have defects in ESR1.
In the maiden trial, comparism was made between the effectiveness of a standard aromatase inhibitor drug known as exemestane which works by blocking oestrogen synthesis and fulvestrant drug which degrades the oestrogen receptor protein so as not to feed the tumour.

Almost 40 per cent of the 162 patient blood samples for the trial were discovered to have mutations in the oestrogen receptor. These women responded better to fulvestrant, which delayed progression of the disease for 5.7 months, compared to 2.6 months on exemestane.
For women without ESR1 mutations who received both treatments, fulvestrant and exemestane, had the same effectiveness.
In the second trial, that used treatment with fulvestrant and a placebo to fulvestrant and palbociclib, it was found that 25.3 per cent of patient blood samples had oestrogen receptor mutations going into this trial. But because palbociclib targets different molecules, the patients had the same outcomes regardless of whether or not they had the mutation in the oestrogen receptor.

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The team leader, Dr Nicholas Turner, Team said their “results show that breast cancer with and without ESR1 mutations are distinct subtypes that respond differently to treatment. These subtypes can be diagnosed simply and cheaply from a blood test, and should be considered for future clinical trials of advanced breast cancer to ensure patients are receiving the best treatment for their cancer.” He added further that “for the first time we should able to use a potentially simple test to help us pick the best treatment for women with advanced cancer after their initial treatment has failed. We do need to confirm the results in another trial before we can implement this clinically.”
In his view, Professor Paul Workman, noted that “cancer drug resistance is the biggest challenge we face in defeating the disease. This fantastic new research demonstrates how a relatively simple blood test can be used, not only to detect mutations that could lead to resistance, but to precisely target treatments to the genetic changes in individual tumours as part of personalised, precision therapy.

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