A study that tested a new approach to analysing circulating tumour cells (CTCs) in patients with breast cancer, with the aim of guiding treatment decisions was the winning presentation at the recent NIHR Leicester BRC Symposium.
The lead researcher, Rebecca Allsopp, travelled to Salt Lake City in the USA last week to present her findings at the Association of Molecular Pathology.
Breast cancer is the most common cancer in women worldwide and is the leading cause of cancer-related deaths in women. Genetic profiling of breast tumour tissue can help to identify genetic changes that take place, with new treatments being developed based on this specific knowledge.
In this full study, which was published in Clinical Chemistry earlier in 2023, a team of researchers within the NIHR Leicester BRC at the University of Leicester in collaboration with NIHR BRC researchers at Imperial College London, examined changes known as ‘somatic copy number alterations’ in individual CTCs.
Rebecca explained: “Copy number alterations can provide us with useful information to potentially guide treatment decisions
“We wanted to see whether there was a quick, cost-effective way of identifying whether these specific genetic changes are present in the cancer cells circulating in a patient’s blood.
“We tested the effectiveness of a shallow depth approach which looks at a small proportion of the DNA recovered from individual circulating tumour cells.”
Study participants included 50 healthy women without cancer, 105 patients with metastatic breast cancer and 23 patients on follow-up after their breast cancer surgery.
Circulating tumour cells were isolated from blood collected and DNA from individual cells was compared with 300 picograms of paired plasma cell free DNA (cfDNA) using the Ion ReproSeq PGS Kit (Thermo Fisher Scientific).
Rebecca said: “Based on our analyses, the shallow whole genome sequencing process was able to detect changes in regions containing genes of interest for guiding therapies; notably MYC, FGFR1, and ERBB2.
“The approach we used has some clear clinical advantages:
- Only picogram amounts of cfDNA are required for testing – such low-volume samples are present in blood spots, which could be collected by patients in their homes
- It requires no prior knowledge about characteristics of the primary tumour or metastases
- A fast turnaround time of under 48 hours.
- Low cost of around £100 per sample.”
Rebecca added: “Really interestingly, in this study, this method was able to detect genomic instability in the three primary breast cancer patients that subsequently clinically relapsed. In one of these cases, the blood sample was taken 2 and a half years ahead of relapse.”
“I’m really proud to have been awarded best presentation by the NIHR Leicester BRC, and also to have presented my findings in the USA.
“Our findings have the potential for this to be used as a screening tool, identifying patient samples eligible for wider analyses of other markers, for example, methylation changes of plasma DNA. By covering as many parameters as possible, liquid biopsies will evolve to a clinically vital tool improving the management of the patient’s disease.”
For the full paper, please click here.