News in Science

Breast cancer's stealth mechanism revealed

Cancer pathway Australian researchers have discovered a mechanism that allows some breast cancer cells avoid the immune system and form secondary cancers in other parts of the body.

Their findings raise hopes that new or existing drugs could one day be used to restore the normal immune response against these cells, and stop cancers from spreading.

Dr Belinda Parker from the Peter MacCallum Cancer Centre in Melbourne and colleagues set out to understand why some cancer cells spread to different tissues, a process known as metastasis.

In some cases, cancer cells have already spread to other tissues when patients with breast cancer first arrive for treatment, explains Parker.

"Quite a high proportion of patients will have cancers cells that have left the breast when they are first diagnosed, although it can be quite a few years before they grow into cancer," she says.

But once a cancer has spread from its original site it can be harder to treat, which makes a good outcome less likely.

"If we can understand the mechanisms of cancer cell spread to distant tissues, hopefully we can use that information to identify patients whose cancer is likely to spread, and develop new drugs or use existing drugs to treat these patients," says Parker.

In laboratory mice, the researchers found that breast cancer cells which spread to the bone developed a means of avoiding the immune system, silencing a particular immune signal that normally kept them in check.

Their finding appears today in the journal Nature Medicine.

Comparing the expression of genes in primary tumour cells against those that had spread to the bone, the researchers found that a number of genes relating to immune system molecules called interferons were suppressed in the bone metastases.

When the researchers restored the expression of those genes in the tumour cells, or administered interferon to the mice, bone metastases were reduced and the mice lived for longer without metastases.

Identifying risk

Parker hopes that the new discovery could help identify breast cancer patients who are at risk of their cancer spreading to the bone. "Measuring the loss of this immune signal in a given patient's primary tumour may allow us to predict an increased risk of spread to the bone, so these patients can be monitored for spread," she says.

It may also be possible to treat patients who are at higher risk of such spread with interferon to help the immune system fight the metastatic cells, she says. Interferons are already used in other conditions including some cancers, multiple sclerosis and hepatitis, although they do carry a risk of significant side effects.

"Stimulating this immune response has the potential for combination with immunotherapies and chemotherapy," says Parker.

The researchers are now exploring these opportunities, looking specifically at when this kind of treatment would be most useful.

"We think it is most likely to be valuable in the early stage of disease, when you can hopefully eliminate the cancer cells hiding around the body."