Testing breast cancer cells for how closely they resemble stem cells could identify women with the most aggressive disease, a new study suggests.
Researchers found that breast cancers with a similar pattern of gene activity to that of adult stem cells had a high chance of spreading to other parts of the body.
Assessing a breast cancer's pattern of activity in these stem cell genes has the potential to identify women who might need intensive treatment to prevent their disease recurring or spreading, the researchers said.
Adult stem cells are healthy cells within the body which have not specialised into any particular type, and so retain the ability to keep on dividing and replacing worn out cells in parts of the body such as the gut, skin or breast.
A research team from The Institute of Cancer Research, London, King's College London and Cardiff University's European Cancer Stem Cell Research Institute identified a set of 323 genes whose activity was turned up to high levels in normal breast stem cells in mice.
The study is published today (Wednesday) in the journal Breast Cancer Research, and was funded by a range of organisations including the Medical Research Council, The Institute of Cancer Research (ICR), Breakthrough Breast Cancer and Cancer Research UK.
The scientists cross-referenced their panel of normal stem cell genes against the genetic profiles of tumours from 579 women with triple-negative breast cancer - a form of the disease which is particularly difficult to treat.
They split the tumour samples into two categories based on their 'score' for the activity of the stem cell genes.
Women with triple-negative tumours in the highest-scoring category were much less likely to stay free of breast cancer than those with the lowest-scoring tumours. Women with tumours from the higher-scoring group had around a 10 per cent chance of avoiding relapse after 10 years, while women from the low-scoring group had a chance of around 60 per cent of avoiding relapse.
The results show that the cells of aggressive triple-negative breast cancers are particularly 'stem-cell-like', taking on properties of stem cells such as self-renewal to help them grow and spread. They also suggest that some of the 323 genes could be promising targets for potential cancer drugs.
Study leader Dr Matthew Smalley, Deputy Director of the European Cancer Stem Cell Research Institute and Reader within Cardiff University's School of Biosciences, 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."
Study co-author Professor Clare Isacke, Professor of Molecular Cell Biology at 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."
Dr Matthew Lam, Senior Research Officer at Breakthrough Breast Cancer, said: "Women with triple negative breast cancer tend to have higher rates of recurrence than those with other types of breast cancer.
"There is so much more to learn about this particularly aggressive form of the disease which is why this type of research is so important. If we can develop ways to predict who is most likely to relapse, more can be done to protect high-risk patients, such as closer monitoring or extended treatment, to help reduce the chance of their cancer coming back."
Dr Nathan Richardson, Head of Molecular and Cellular Medicine at the Medical Research Council, said: "Triple negative breast cancers are a particularly challenging form of the disease to treat. Casting a light on to the genetic factors that are behind the recurrence and spread of cancer is crucial to understanding more about the biology of this aggressive disease.
"This study could be hugely important to find ways to identify those patients who are at risk of the most aggressive forms of the disease, improving the way they are monitored and cared for. Crucially, this research could lead to new treatments with the potential to make a real difference for women with this type of breast cancer."
Notes to editors
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The Institute of Cancer Research, London, is one of the world's most influential cancer research institutes.
Scientists and clinicians at The Institute of Cancer Research (ICR) are working every day to make a real impact on cancer patients' lives. Through its unique partnership with The Royal Marsden NHS Foundation Trust and 'bench-to-bedside' approach, the ICR is able to create and deliver results in a way that other institutions cannot. Together the two organisations are rated in the top four cancer centres globally.
The ICR has an outstanding record of achievement dating back more than 100 years. It provided the first convincing evidence that DNA damage is the basic cause of cancer, laying the foundation for the now universally accepted idea that cancer is a genetic disease. Today it leads the world at isolating cancer-related genes and discovering new targeted drugs for personalised cancer treatment.
As a college of the University of London, the ICR provides postgraduate higher education of international distinction. It has charitable status and relies on support from partner organisations, charities and the general public.
The ICR's mission is to make the discoveries that defeat cancer. For more information visit http://www.
European Cancer Stem Cell Research Institute
Cancer stem cells offer the potential to transform the way that cancer is tackled and the European Cancer Stem Cell Research Institute at Cardiff University is the only institute in Europe solely dedicated to research into this concept.
There is evidence that cancer stem cells play a key role in the creation and growth of tumours, and the way they spread around the body. If this is correct, it may be possible to treat cancer more effectively by focusing therapy at the stem cell, rather than all the cells in the tumour, as current treatments do.
Led by the Institute Director, Professor Alan Clarke, the Institute provides a state-of-the-art research environment for senior academics, Research Fellows and postgraduate students to interact. New early career Research Fellows have been recruited to work alongside world-leading teams in basic biomedical science and drug development to create a UK-based hub of research excellence to target cancer.
The European Cancer Stem Cell Research Institute establishes Cardiff University as an international leader in the field of cancer stem cell research. It is opening up possibilities for the development of tailored therapy per patient (known as 'stratified' or 'personalised' medicine) which is predicted to change the landscape of both research and therapy over the coming years.
Cardiff University is recognised in independent government assessments as one of Britain's leading teaching and research universities and is a member of the Russell Group of the UK's most research intensive universities. Among its academic staff are two Nobel Laureates, including the winner of the 2007 Nobel Prize for Medicine, University Chancellor Professor Sir Martin Evans. Founded by Royal Charter in 1883, today the University combines impressive modern facilities and a dynamic approach to teaching and research. The University's breadth of expertise encompasses: the College of Arts, Humanities and Social Sciences; the College of Biomedical and Life Sciences; and the College of Physical Sciences and Engineering, along with a longstanding commitment to lifelong learning. Cardiff's four flagship Research Institutes are offering radical new approaches to cancer stem cells, catalysis, neurosciences and mental health and sustainable places.
Breakthrough Breast Cancer works to stop breast cancer for good by improving early diagnosis, developing new treatments and preventing all types of breast cancer.
Breast cancer is not yesterday's problem; it's a disease that affects more women every year. Breakthrough Breast Cancer is working harder than ever before to stop women getting, and dying from, the disease.
Over the last 15 years, we've invested £100 million into cutting-edge research - research that has resulted in major breakthroughs, some of which are now in clinical trials. We currently fund the work of more than 270 research scientists across the UK, with many based in the ground-breaking Breakthrough Toby Robins Breast Cancer Research Centre in London.
The Breakthrough Generations Study - set up in 2004 - is world's largest and most comprehensive study into the causes of breast cancer and is following more than 113,000 women throughout their lives.
Breakthrough Breast Cancer and Breast Cancer Campaign are joining forces in 2015 to become the UK's largest breast cancer research charity. Our joint ambition is that by 2050, no one will die from breast cancer - find out more.
For more information about Breakthrough Breast Cancer, visit breakthrough.org.uk or follow us on Twitter or on Facebook