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Proteins Predict Breast Cancer Survival After Tamoxifen

Better survival in women with high expression of estrogen receptor, low expression of protein activating receptor

WEDNESDAY, May 17 (HealthDay News) -- Women whose breast cancers have high expression of the estrogen receptor and low expression of p21-activated kinase 1 (Pak1) protein, which activates estrogen receptors, have better recurrence-free survival after treatment with tamoxifen, according to a report in the May 17 issue of the Journal of the National Cancer Institute.

Goran Landberg, M.D., Ph.D., of Lund University in Malmo, Sweden, and colleagues measured the expression of Pak1 in 403 primary breast tumors from women who had been randomized to either no treatment or adjuvant treatment with tamoxifen for two years. The researchers also performed experiments on cultured cells to examine the relationship between Pak1 expression and tamoxifen responsiveness.

The researchers found that women who had been treated with tamoxifen and whose tumors were estrogen receptor alpha-positive with low Pak1 expression had significantly better recurrence-free survival than women receiving no treatment (hazard ratio 0.502). Overexpression of Pak1 in breast cancer cells inhibited the response to tamoxifen, while tamoxifen induced the expression of nuclear Pak1 and increased the protein's activity in tamoxifen-resistant human endometrial cancer cells.

"The clinical correlations reported by Holm et al. indicate that packing tumor cell nuclei with Pak can perturb tamoxifen's action," V. Craig Jordan, Ph.D., D.Sc., of Fox Chase Cancer Center in Philadelphia, writes in an accompanying editorial. "The tumor, once 'Paked up,' has no alternative but to grow."

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