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Fishing for cancer clues in liquid biopsies

We’re finding new ways to outsmart breast cancer every day but sometimes it can still feel like we’re dealing with a disease that’s always one step ahead of us. Fortunately, a new technique is giving us a better head start on cancer’s next move. By picking up potential relapses earlier and helping scientists to see how someone’s cancer is behaving on a molecular level, the ‘liquid biopsy’ is making waves in the breast cancer research world.

Going with the flow

Biopsies traditionally involve surgery or needles to remove a sample of a patient’s tumour, which is then analysed to learn more about their cancer. Liquid biopsies enable that analysis without the need for surgery and its associated risks, time, and discomfort, by fishing out bits of cancer that have made their way into a patient’s blood, urine or saliva.

From a small amount of blood, researchers have found a way to isolate the DNA that gets released during the day-to-day growth and death of cells in a breast tumour. To separate this cancer DNA from other DNA in the blood, scientists look for the genetic mutations that are only present in cancer DNA.

Trickling down to the right treatment

The mutations that set cancer DNA apart are also what scientists want to analyse to learn more about a patient’s cancer and better tailor their treatment. Some, if not all, of these mutations are the drivers that are giving cancer cells instructions that make them grow out of control. This growth can be stopped with treatments that have been designed to exploit these specific mutations.

This targeted approach to treatment, guided by liquid biopsies, could be particularly useful in secondary breast cancer. Fewer people have surgery to remove secondary tumours so getting samples for a traditional biopsy is not always possible, but liquid biopsies could fill this gap.

Multiple studies have now looked into the possibility of using liquid biopsies to benefit secondary breast cancer patients. Recently, research part-funded by Breast Cancer Now, used liquid biopsies to look for mutations in a panel of 16 genes that can drive breast cancer growth when mutated. The researchers, led by Professors Jacqui Shaw and Justin Stebbing, were able to identify mutations in blood samples from 21 of 42 women in the study and, importantly, in 9 women, the mutations found via their liquid biopsies could have led to a change in their treatment.

However, no one has yet provided the evidence that selecting targeted treatments for patients based on their liquid biopsy results can actually improve their outcomes. As Dr Nick Turner, Head of the Molecular Oncology team at the Breast Cancer Now Toby Robins Research Centre, London, explains: “We need to show there is evidence for this for it to then become standard practice.”

Fortunately, Dr Turner’s team at the Royal Marsden and colleagues across the country have recently launched a trial, called plasmaMATCH, which hopes to provide this evidence by matching women with secondary breast cancer with a targeted treatment – via a liquid biopsy.

With this trial, and other work internationally, Dr Turner believes that, “it’s a realistic expectation,” that we will have enough evidence to take liquid biopsies into routine use in the clinic for secondary breast cancer “in the next year or two.”

Moving upstream - predicting recurrence

Looking further into the future, liquid biopsies could also be used to get a step ahead of early breast cancer following a patient’s initial surgery for the disease.

Dr Turner explains: “What people are excited about in the future is whether techniques for secondary breast cancer can be used for primary breast cancer. Recent results have shown we might be able to use the same test to see who isn’t cured and so needs further treatment after surgery.”

In this scenario, liquid biopsies could be used to get an indication that cancer is growing in the body before this is even detectable on scans or by symptoms. In fact, in recent work by Dr Turner’s group, liquid biopsies gave, on average, a 7.9 month head start on increased tumour activity before secondary tumours were picked up by symptoms or scans.

The hope is that if patients can be offered treatment at this very early stage, it would be more successful than when it is currently given. Treatments, as with secondary cancer, could also be selected based on the mutations that appear in an individual’s cancer – again giving a better chance of treatment being effective and stopping cancer in its tracks.

Beyond stopping cancer there is also some evidence that we could one day use liquid biopsies as a screening tool to find cancer in the first place, although testing would have to get more robust and cheaper for this to happen on a large-scale.

Flowing into the future

The regular use of liquid biopsies in the clinic may be a few years off yet, but it’s clear why much is being made of this technique in the research world - with new results steadily coming in and the exciting plasmaMATCH trial opening in the UK.

And what’s fuelling that excitement is hope - our hope to get ahead of cancer before it takes lives, and to outsmart it with treatment choices that aren’t guided by surgical knives or biopsy needles, but by the wealth of information in a small amount of blood.




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