Tamoxifen resistance among women with breast cancer may be related to low levels of the protein Rho GDI-alpha in these patients.

Tamoxifen resistance develops in some women with estrogen-receptor-positive tumors. To learn why, a team led by Suzanne Fuqua, PhD—professor of medicine at the Lester and Sue Smith Breast Center at Baylor College of Medicine in Houston, Texas—compared two groups of ER-positive tumors: four from women who used tamoxifen and did not have a recurrence, and five from women whose cancer spread while they were taking the drug.

Rho GDI-alpha was underexpressed in the women with tamoxifen-resistant metastatic disease. In addition, levels of another protein—MTA2—rose markedly when Rho GD1-alpha dropped. Fuqua and associates noted that combined levels of the two proteins were associated with recurrence in 250 tamoxifen-treated patients.

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“These are the first data suggesting a tight, clinically important connection between the two pathways—Rho GDI-alpha and MTA 2,” wrote the investigators in their report, published online by the Journal of the National Cancer Institute. “Our data also suggest a possible mechanism, in which the loss of Rho GDI-alpha function promotes distant progression of breast tumors by triggering downstream molecules, such as MTA2, with metastasis-promoting activities.”