Test Predicts Risk of Breast Cancer Recurrence

These findings were reported in the online edition of The New England Journal of Medicine on December 10, 2004.

The test is based on levels of expression of a panel of cancer-related genes. Researchers used tissue samples and medical records from women enrolled in clinical trials of the cancer drug tamoxifen, which blocks the effect of estrogen on breast cancer cells. Using samples from 447 patients and a collection of 250 genes in three independent studies, 21 cancer-related genes were found that worked best. The scientists created a formula that generates a recurrence score based on the expression patterns of these genes in a tumor sample. The recurrence score ranged from 1-100.

Using biopsy tissue and medical records from another tamoxifen trial, researchers divided 668 women into low, intermediate, and high risk-of-recurrence groups: 51% were in the low-risk group (a recurrence score of less than 18); 22% were at intermediate risk (18 or higher but less than 31); 27% were at high risk (31 or higher). These correlated well with the actual rates of recurrence after 10 years. In the low-risk group, there was a 6.8% rate of recurrence at 10 years. In the intermediate and high-risk categories, these rates were 14.3 and 30.5%, respectively.

The same test, called Oncotype DX, was also used to predict how beneficial chemotherapy would be for these women. They found that women with high recurrence scores (about 25% of patients) had a large benefit in terms of 10-year recurrence-free rates, while women with low recurrence scores (about 50% of patients) derived minimal benefits. The intermediate-risk group was too small to make a determination.

"The test has the potential to change medical practice by sparing thousands of women each year from the harmful short- and long-term side effects associated with chemotherapy,” noted JoAnne Zujewski, M.D., senior investigator in the Cancer Therapy Evaluation Program of the U.S. National Cancer Institute, which collaborated on the study with Genomic Health, Inc. (Redwood City, CA, USA).

Researchers at Genomic Health developed a method for performing the analyses on tissues embedded in paraffin wax, allowing them to use the altered RNA found in fixed tissue. Prior to this research, analysis of gene expression was performed on specimens that were frozen rather than on tissue prepared for routine pathologic evaluation.



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