Researchers Find Possible Clues to Tamoxifen Resistance in Breast Cancer

Extract

Breast cancer patients who become resistant to tamoxifen may have low levels of a protein called Rho GDI-alpha, according to a study published online March 30 in the Journal of the National Cancer Institute.

Women whose tumors have estrogen receptors (ERs) often take tamoxifen after surgery to prevent recurrence of the cancer and keep it from metastasizing to other parts of the body. Some patients, however, become resistant to the drug even though their tumors remain ER-positive.

To explore the mechanisms of this resistance, Suzanne Fuqua, Ph.D., professor of medicine in the Lester and Sue Smith Breast Center at Baylor College of Medicine in Houston and colleagues compared two groups of ER-positive tumors: four primary tumors from women who took tamoxifen and did not have a recurrence and five metastatic tumors from women taking tamoxifen whose tumors spread while they were on the drug. The authors found that Rho GDI-alpha was under-expressed—its levels were low—in the women with tamoxifen-resistant metastatic disease. They validated the association of low Rho GDI-alpha with tamoxifen resistance in laboratory cells, in human tumors implanted in mice, and in genetic data from 250 women whose ER-positive breast tumors were treated with tamoxifen.