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Science Translational Medicine: Iron Regulation Linked to Breast Cancer Survival Rate

Changes in iron regulation may be an important driver of the growth and spread of breast cancer, and could possibly be used to predict the survival of women with breast cancer, a new Science Translational Medicine study in mice suggests.

Although iron is needed by virtually all cells to grow, this powerful metal can wreak havoc if not tightly regulated in cells. Now, Frank Torti and colleagues and Wake Forest University Baptist Medical Center show that levels of ferroportin—a protein that exports iron from cells—is linked to the likelihood that cancer will spread to other parts of the body and may be a telltale sign of patient outcome.

Using ferroportin as a marker for iron regulation may thus be a useful tool in breast cancer prognosis and may even help direct therapy. In the future, manipulating levels of ferroportin or proteins that affect levels of ferroportin may also prove to be an effective breast cancer treatment.

In the study, the researchers found that ferroportin levels are strikingly lower in breast tumors than in normal tissue. Without enough ferroportin to shuttle iron out of cells, a detrimental build up of “free” iron occurs.

Yet, Torti and colleagues found that this process is alterable; human breast tumors in mice that had ferroportin levels restored to normal grew more slowly than tumors with low ferroportin levels.

Next, the team looked at gene expression profiles of over 800 women with breast cancer. By determining levels of ferroportin and another iron-related protein called hepcidin, the researchers were able to group the women based on the likelihood of their cancer spreading. From these data, the researchers found that low ferroportin levels are a strong predictor of a poor outcome for women with breast cancer. On the positive side, they also show that having breast cancer with high ferroportin levels is a promising sign for a patient, predicting a 90% 10-year survival rate.

Exactly why high amounts of free iron in cells prompts cancer to be more aggressive remains murky, but these results show that changes in iron handling in breast cancer strongly contribute to cancer growth.

Science Translational Medicine, the newest journal from Science, focuses on outstanding science with promise to improve human health and quality-of-life. Under the direction of Elias Zerhouni, chief scientific adviser and former director of the National Institutes of Health, and Editor Katrina Kelner, the journal aims to publish groundbreaking research from basic biology that will help make significant advances in medical care, along with commentary on the latest issues in translational medicine.