Testing breast cancer cells for how closely they resemble stem cells could identify the most aggressive cases of the 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 say.
Adult stem cells are healthy cells within the body that have not specialized 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 new genetic test?
The research team identified a set of 323 genes whose activity was turned up to high levels in normal breast stem cells in mice.
The scientists cross-referenced their panel of normal stem cell genes against the genetic profiles of tumors from 579 women with triple-negative breast cancer—a form of the disease that is particularly difficult to treat.
“Triple negative breast cancer accounts for around 15 percent 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,” says study leader Matthew Smalley, deputy director of the University of Cardiff’s European Cancer Stem Cell Research Institute.
“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.”
‘Stem cells gone bad’
The researchers split the tumor samples into two categories based on their “score” for the activity of the stem cell genes.
Women with triple-negative tumors in the highest-scoring category were much less likely to stay free of breast cancer than those with the lowest-scoring tumors.
Women with tumors from the higher-scoring group had around a 10 percent chance of avoiding relapse after 10 years, while women from the low-scoring group had a chance of around 60 percent 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. The findings also suggest that some of the 323 genes could be promising targets for potential cancer drugs.
“Cancer cells can behave very much like stem cells—but stem cells gone bad,” says coauthor Clare Isacke, professor of molecular cell biology at the Institute of Cancer Research, London.
“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 personalizing treatment.”
The study appears in the journal Breast Cancer Research, and was funded by several organizations including the Medical Research Council, The Institute of Cancer Research (ICR), Breakthrough Breast Cancer, and Cancer Research UK.
Source: Cardiff University