Elevated levels of a protein found in breast tumors may help identify women who have cancer that is likely to spread, according to researchers at the University of Texas M.D. Anderson Cancer Center in Houston.

This new molecular tag may help physicians determine which breast cancer patients need more aggressive treatment and which can be spared treatment with chemotherapy.

High levels of a protein called cyclin E are closely linked with aggressive, invasive breast cancer. The study used tissue samples of current and former breast cancer patients to show that cyclin E is a better predictor of patient outcome than any other predictive marker.

However, the study must be repeated with newly diagnosed patients to determine its true predictive value, according to Khandan Keyomarsi, PhD, associate professor in experimental radiation and co-author of the study.

Researchers looked for the presence of cyclin E because when this protein is found at high levels inside cancer cells, it signals the cells to multiply continuously. In normal cells, cyclin E is present for a brief time and helps keep cell division under control. The researchers also found smaller versions of cyclin E that are not found in normal cells. These low molecular weight versions are produced by an enzyme that cuts up the normal cyclin E and creates a new form that is even more adept in getting cells to divide.

"We have shown the occurrence of low molecular weight forms of cyclin E that are not found in normal cells and are present throughout cell cycle in cancer cells," said Keyomarsi. "These abnormal forms of cyclin E are always giving the "go" signal, telling cells to divide."

Researchers examined tissue from tumors from 395 women with breast cancer. In patients with stage one breast cancer, about 10 percent had high levels of cyclin E in their cancer cells. All of those patients had died from a recurrence of breast cancer within five years of diagnosis, while none of the women who had low levels of cyclin E had died. The proportion of tumors that had high levels of cyclin E increased with increasing extent of disease, according to the report published in the New England Journal of Medicine.

"This study shows that the presence of low molecular weight forms of cyclin E has a very powerful prognostic value," said Keyomarsi. "However, we have to validate the study using newly diagnosed patients in which we are blinded to the diagnosis. We are in the midst of that study now. If it bears out our initial results, we will try to get it into the clinic as soon as possible, though it may be at least one year."

"My hope is that this technique may help ease the burden of chemotherapy among breast cancer patients," continued Keyomarsi. "Women who don't overexpress cyclin E may not need chemotherapy, which kills all dividing cells and can do significant damage to other tissues and organs." For women who have high levels of cyclin E, more aggressive treatment would be indicated.

Other sources: M. D. Anderson Cancer Center