The current state of play in developing liquid biopsies for breast cancer was described at Breast Cancer Trials’ Annual Scientific Meeting in Hobart by Professor Sarah-Jane Dawson from the Peter MacCallum Cancer Centre in Melbourne.
A liquid biopsy is a blood test that looks for materials, such as circulating tumour cells (CTCs) or cell-free circulating tumour DNA (ctDNA) released by breast cancer tumours into the bloodstream.
In breast cancer, ctDNA could provide information to help with early detection, molecular profiling, detecting minimal residual disease, detecting relapses and monitoring responses to therapy.
In New Zealand, ctDNA tests for breast cancer are available but used primarily for research purposes rather than routine clinical practice. You can read more about one such study at Christchurch Hospital here.
Professor Dawson gave an example of ctDNA tests being used to detect PIK3CA mutations in patients involved in the CAPTURE clinical trial, which is looking at whether combining alpelisib with fulvestrant could improve survival in those with metastatic ER positive HER2 negative breast cancer (read more here).
She said that there is interest in using ctDNA analysis for minimal residual disease detection (finding evidence of cancer cells remaining after treatment which are undetectable in standard tissue biopies), but nothing definite has been developed yet. She thought perhaps a customised ‘DNA probe’ based on the original tumour biopsy might be useful and ‘just sequencing everything you find’ could also reveal helpful information. Professor Dawson explained that a difficulty in using ctDNA to find minimal residual disease and guide treatment decisions in early breast cancer is that, with current techniques, finding any ctDNA in a blood sample is an indicator of a poor prognosis in all sub-types of breast cancer. Those with detectable ctDNA often already have metastatic disease or a recurrence.
With regard to using liquid biopsies to monitor treatment effectiveness, Professor Dawson said that levels of ctDNA in patients with metastatic breast cancer do show when a treatment is failing and that they can provide an early indication of treatment resistance. For example, finding ESR1 mutations rising would suggest that using fulvestrant could be helpful.
Professor Dawson also explained that researchers are finding new things to measure in ctDNA samples that could inform future analyses. Gene copy number, DNA fragment lengths, and whole genome sequences can be analysed. ‘Fragmentomics’ looks at fragmentation patterns in ctDNA. Epigenomic processes (which switch genes on and off) can also be analysed to gather information that could be useful in cancer diagnosis and treatment.
Analysis of ctDNA is clearly a very active area of research, which could be practice-changing in the future.
16 August 2025
