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Genomic tests improve prediction of breast cancer response to chemotherapy, hormonal therapy

minimal residual disease after treatment. The team is studying minimal residual disease further. Pusztai said the positive predictive value is an improvement over current predictions based on pathologic characteristics of the cancer.

About 70 percent of breast cancers express the estrogen receptor (ER), but tamoxifen and other anti-estrogen therapies only benefit about half of these patients. The challenge is to predict exactly who will be helped and who should seek other treatment.

Researchers focused on the influence of estrogen receptor activity on the expression of downstream genes. "We defined the 200 strongest ER-related genes and developed from those a Sensitivity to Endocrine Therapy (SET) index to actually measure this activity of ER," says W. Fraser Symmans, M.D., associate professor in the Department of Pathology.

The ability of the SET index to predict the benefit of hormonal therapy was then tested in 267 patients who received tamoxifen without chemotherapy for five years after surgery. "There was a strong relationship between their SET index score and the probability of there being no disease 10 years later," Symmans said.

Scoring in the top 35 percent of the index was significantly associated with excellent distant relapse-free survival at 10 years. Patients who scored in the lower 50 percent of the index derived little benefit from tamoxifen alone and, in a separate analysis, were shown to more likely benefit from chemotherapy.

An intermediate group, who scored in the 50th-65th percentile, initially benefited from five years of tamoxifen, but their relapse rate began to increase about two years after treatment ended and eventually approached that of the SET low-scorers.

At five years, about 92 percent of both high and intermediate SET index scorers had relapse-free survival, compared with 70 percent for the low SET scorers. At 10 years, however, about 88 percent of high SET scorer
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Contact: Scott Merville
sdmervil@mdanderson.org
713-792-0661
University of Texas M. D. Anderson Cancer Center
14-Dec-2006


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