Gene signature could predict breast cancer aggressiveness
Measuring the activity levels of particular genes in a woman’s breast tumour could identify more aggressive forms of the disease, according to a team of UK scientists.
"This intriguing finding is another piece in the complex jigsaw puzzle that breast cancer researchers are working hard to solve." - Henry Scowcroft, Cancer Research UK
The team, made up of researchers from The Institute of Cancer Research in London, King’s College London, and Cardiff University, tested different triple-negative breast cancer samples for patterns of gene activity similar to that seen in specialised cells known as stem cells.
Stem cells are healthy, unspecialised cells that divide and replace worn out cells in parts of the body, such as the bowel, skin and breasts.
The team found that triple-negative breast tumours that bore a ‘stem-cell-like’ signature were more likely to come back after treatment.
Henry Scowcroft, science information manager at Cancer Research UK – which part-funded the research – called the finding "another piece in the complex jigsaw puzzle" being solved by breast cancer researchers - adding that further work is needed to confirm its findings.
Initially, the researchers identified a signature of 323 genes that were highly active in normal breast stem cells in mice.
They then cross-referenced this gene signature against the genetic profiles of tumours from 579 women who had ‘triple-negative’ breast cancer - a form of the disease that can be particularly difficult to treat.
The tumour samples clustered into two categories: those with a similar signature to stem cells, and those that were less stem cell-like.
Women whose tumours were more stem-cell like were also more likely to have had a poorer prognosis: they had a 10 per cent chance of staying disease-free for at least 10 years, compared with a 60 per cent chance for women with the least stem cell-like tumours.
Dr Matthew Smalley, deputy director of Cardiff University's European Cancer Stem Cell Research Institute, who led the study, said: "Triple-negative breast cancer accounts for around 15 per cent of breast cancers, but is more difficult to treat than other cancer types as it is not suitable for treatments such as anti-hormonal therapy.
"It's particularly important to understand the genetic factors that help it to spread around the body - and we were excited to find that a key factor seems to be the degree to which gene activity resembles that of stem cells.
"Although our work is not yet ready for clinical use, our next step will be to explore which of these 323 genes are the most important drivers of the disease and to use these to develop a new genetic test."
Cancer Research UK’s Henry Scowcroft added that the study adds to the growing, complex picture of breast cancer with the disease being split into different types “each with different genes involved, and different clinical behaviours”.
“The prize for solving this puzzle is better, more personalised treatment, and even better outcomes for women who develop the disease.
"Although this study needs further work to confirm its findings and test its implications, it’s a welcome advance in our understanding of this terrible disease, which – despite huge improvements in recent years – still claims the lives of more than 30 women every day,” he added.
Co-author Professor Clare Isacke, from the Institute of Cancer Research, London, said: "Cancer cells can behave very much like stem cells - but stem cells gone bad. They find a way to activate genes which are usually only turned up in normal stem cells, giving them characteristics - such as self-renewal and immortality - that make them more difficult to treat.
"Our study could ultimately help lead to a genetic test assessing breast cancer cells for how closely they resemble stem cells. Picking out women with this type of aggressive disease could give us new ways of personalising treatment."
The study was funded by the Medical Research Council, The Institute of Cancer Research, Breakthrough Breast Cancer and Cancer Research UK, and is published in the journal Breast Cancer Research.