National Cancer Institute, www.cancer.gov
The Nation's Progress in Cancer Research: An Annual Report for 2003
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TUMOR CELL PROTEIN PREDICTS BREAST CANCER SURVIVAL

A newly identified molecular marker appears to be a powerful predictor of poor outcome in breast cancer patients. The presence of the protein, cyclin E, which scientists found in high levels in tumors that had recurred or spread, could indicate which patients are most likely to benefit from aggressive treatment, while sparing others from unnecessary, potentially toxic chemotherapy.


 

Low levels of cyclin E in cancer cells is apparently a much better predictor of survival than other commonly recognized predictors, such as lymph node status, according to an NCI-supported study by Khandan Keyomarsi, Ph.D., and colleagues at the M. D. Anderson Cancer Center. Their study found that cyclin E levels could help identify a patient whose prognosis is poor, even when her cancer has not spread to the lymph nodes.

In normal cells, cyclin E is an important regulator of the cell division cycle. In tumor cells, however, cyclin E is often overabundant. This over-expression is often associated with an aggressive form of cancer. In addition, the full-length form of cyclin E can generate low molecular weight versions of itself, found only in cancer cells, which are linked to even more rapid cell division. The presence of high levels of both forms of cyclin E is significantly associated with poor outcome in breast cancer patients.

Keyomarsi's retrospective study examined tumor tissues from 395 breast cancer patients. About 10 percent of women with stage I disease had high levels of cyclin E, and all of them died of recurrence within 5 years of diagnosis. None of the stage I patients with low cyclin E levels died within the same time period. The strong link between high cyclin E levels in stage I disease and poor prognosis suggests that these protein forms may play a specific role in the development of a malignant tumor.

"If this apparent correlation with aggressive breast cancer bears out, cyclin E analysis could provide a way to apply treatments and surveillance appropriately to the most at-risk patients," says Barbara Spalholz, Ph.D., chief of the Cancer Cell Biology Branch of NCI's Division of Cancer Biology.

A separate study suggests that cyclin E may be a marker for ovarian cancer, as well. Additional studies are under way including a prospective study of breast cancer patients to validate cyclin E's predictive value. Other research is focusing on the protein's unknown biological mechanisms to determine if cyclin E is a cause of, or merely correlated with, cancer's aggressiveness. If cyclin E is a direct cause of aggressive breast cancer, it could be a target for new treatments.


Keyomarsi K, Tucker SL, Buchholz TA, Callister M, Ding Y, Hortobagyi GN, Bedrosian I, Knickerbocker C, Toyofuku W, Lowe M, Herliczek TW, Bacus SS. Cyclin E and survival in patients with breast cancer. New England Journal of Medicine, November 14, 2002; 347(20):1566-1575.

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