‘Liquid biopsy predicts early breast cancer progression’ – Written by Charlotte Harrison, Science Writer.
Researchers from Johns Hopkins University have shown that a new liquid biopsy test based on gene methylation levels can predict whether a patient’s breast cancer will progress as early as one month after they start treatment. The findings of the prospective biomarker study in 144 women with advanced breast cancer were published in the journal Clinical Cancer Research.
“It looks promising that we can detect methylation in the first four weeks of treatment,” said study author Kala Visvanathan in a press release.
“Currently, we wait until we see symptomatic or clinical changes, usually within three months, before adjusting treatments. If we could detect changes earlier, we could adjust treatments earlier, if necessary, with the goal of achieving better clinical outcomes and prolonging survival,” she said.
Methylation changes
The assay detected methylation in nine genes commonly altered in breast cancer, namely AKR1B1, TM6SF1, ZNF671, TMEFF2, COL6A2, HIST1H3C, RASGRF2, HOXB4 and RASSF1, as well as ZNF671 which is associated with oestrogen receptor-negative breast cancer.
Plasma samples were collected from patients before they started treatment and at 4 and 8 weeks into treatment.
Patients with high cumulative methylation at week 4 had a lower median progression-free survival than those with low cumulative methylation (2.88 months versus 6.66 months). The median overall survival for patients with high cumulative methylation at week 4 was also lower (14.52 months versus 22.44 months).
Moreover, patients with high cumulative methylation at week 4 of treatment had a shorter progression-free survival and poorer overall survival than those who had low cumulative methylation.
Predicting progression
The researchers also looked at the link between cumulative methylation and the patient’s disease status at the first assessment of cancer re-staging. Here, high cumulative methylation at week 4 was associated with progressive disease at restaging. The association remained significant even in the presence of other circulating markers used to monitor disease progression, such as circulating tumour cells.
Based on these overall findings, the researchers used week 4 methylation levels to develop a model that predicted the risk of early disease progression.
To improve the model, the next steps of the research are to work out the best time to measure cumulative methylation by studying methylation patterns each week after patients start treatment. The cancer clinical validity of the liquid biopsy for specific treatments also needs to be determined.
