A team at The Institute of Cancer Research (ICR), London and The Royal Marsden NHS Foundation Trust have shown that liquid biopsies offer accurate, rapid genotyping for adoption into routine clinical cancer care.
Tissue-based vs Liquid biopsies
Tumour mutations are key targets for treatment. In advanced breast cancer, there are some common targetable mutations, such as in PIK3CA. Oncologists can target mutations in this gene with PI3K inhibitors, like alpelisib. Other mutations are rare but also represent attractive therapeutic opportunities, such as HER2 and AKT1 mutations.
Analysis of mutations is often obtained from genomic analysis of tissue-based biopsies from metastatic disease. However, this process is often invasive and the biopsy may not reflect the true tumour heterogeneity. A big challenge is the acquisition of longitudinal tissue biopsies. This is because patients may not present with mutations at the time of relapse but develop them later during treatment.
Alternatively, circulating tumour DNA (ctDNA) offers a scalable and non-invasive approach to profile tumours for somatic mutations. Several retrospective studies have shown high agreement between ctDNA analysis and tumour tissue-based analysis in patients with advanced cancer. On the other hand, prospective studies have shown that there may be substantial discordance in ctDNA testing results. Consequently, this has raised concerns about the widespread adoption of ctDNA testing in the clinic.
In a study, published in The Lancet Oncology, researchers aimed to assess the clinical validity of ctDNA testing. They also wanted to investigate the clinical utility of liquid biopsies in selecting targeted therapies for patients. To do this, they undertook a multicentre, multicohort, phase 2a, platform trial of ctDNA testing in 18 UK hospitals. The trial was known as plasmaMATCH. The team analysed liquid biopsies from over 1,000 women with breast cancer. The participants had previously completed one line of treatment or had relapsed. The researchers looked specifically at three targetable genes – HER2, AKT1 and ESR1 – all known drivers of breast cancer. They gave 142 women with mutations in these genes experimental drugs to target specific characteristics of their cancer.
Overall, the team found that ctDNA testing in advanced breast cancer was highly accurate. There was high agreement between different ctDNA testing techniques and high sensitivity for mutations identified from tissue biopsies. Using ctDNA testing, they were able to detect rare targetable mutations in patients who were then recruited into cohorts that were given targeted therapies (without confirmatory tumour testing). Here, they found that some women with rare HER2 (5 out of 20) and AKT1 (4 out of 18) mutations responded to targeted treatment. These results demonstrate that liquid biopsies can successfully match patients with certain rare forms of advanced breast cancer to more effective treatments.
Professor Nick Turner, study lead and professor of molecular oncology at the ICR, London, stated:
“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.”
Liquid Biopsy Online
Make sure you register for our ‘Liquid Biopsy Online’ webinar series starting on Thursday 1st October. This four-part webinar series will provide you with all you need to know about the liquid biopsy technologies that are about to transform cancer care. Our confirmed speakers include Klaus Pantel, Lauren Leiman, Valerie Taly, Catherine Alix-Panabieres and Jonathan Beer.
Image credit: By xrender – canva.com