Urokinase

Women with breast cancer that hasn't spread to their lymph nodes face a difficult decision: After having surgery to remove tumor tissue from the breast, should they also have chemotherapy? A study in Germany now suggests that an inexpensive test could help determine who would be most likely to benefit from this harsh treatment and who might bypass it.

The researchers studied urokinase-type plasminogen activator (uPA) and its inhibitor, called PAI-1, proteins that are involved in cell migration within the body. Researchers had previously linked high concentrations of the proteins to an increased risk of cancer spreading, or metastasizing.

Among patients who have high concentrations of these proteins in malignant tissue, about one-third die from cancer recurrence within 5 years of the original diagnosis, despite treatment.

Anita Prechtl and her colleagues at the Technical University of Munich measured uPA and PAI-1 concentrations in tumor tissue from 556 breast cancer patients with no detectable cancer in their lymph nodes. The 241 women who had low amounts of these proteins were assigned to receive no further medication after surgery and, in some cases, radiation therapy. Among the 315 women with high protein concentrations, 114 received chemotherapy while 201 didn't.

Among the 241 women in the first group, less than 7 percent had a cancer recurrence during the following 32 months. However, 18 percent of study volunteers with higher amounts of the proteins and no follow-up chemotherapy had their cancer return. Of women with high concentrations of uPA and PAI-1 who got chemotherapy, about 12 percent relapsed, Prechtl reports.

Previous research showed that "by using uPA and PAI-1 as stratification criteria, more than one-half of all node-negative breast cancer patients can be considered to be in a low-risk patient group," she says. "There is little rationale for recommending ... chemotherapy for such a low-risk patient group," she concludes.

"When we look at breast tumors in patients, they look similar. But at the molecular level, they are entirely different," says physician Carlos L. Arteaga of Vanderbilt University in Nashville. Prechtl has been able to distinguish tumors that have high uPA and PAI-1 concentrations from tumors low in these proteins, which are "crucial for the ability of tumor cells to metastasize," Arteaga says. "So biologically, the markers she has addressed make sense."

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