AIB1, Tam, Survival Issues

PRESS RELEASE: Tamoxifen's Effectiveness Depends on Level of Tumor Protein

The effectiveness of the breast cancer drug tamoxifen may depend on tumor expression levels of a protein called AIB1, according to a study in the March 5 issue of the Journal of the National Cancer Institute.

The study found that, in breast cancer patients receiving tamoxifen, high levels of AIB1 were associated with worse disease-free survival.

AIB1 is an estrogen receptor coactivator that is overexpressed in breast cancer cells and is indirectly activated by the HER-2 receptor. Laboratory studies of cells in culture have suggested that cells with high levels of coactivators such as AIB1, or cells with high levels of HER-2 may be more resistant to tamoxifen treatment.

To determine whether high AIB1 expression alone or together with HER-2 reduces the effectiveness of tamoxifen in breast cancer patients, C. Kent Osborne, M.D., of the Baylor College of Medicine and Methodist Hospital in Houston, and his colleagues measured AIB1 and HER-2 protein levels in tumors from 187 patients with breast cancer who had received adjuvant tamoxifen therapy and 119 patients who did not receive adjuvant therapy.

Among patients who did not receive adjuvant therapy, high AIB1 expression was associated with better prognosis and longer disease-free survival.

In comparison to this group, patients who received adjuvant tamoxifen therapy and had high AIB1 expression had poorer disease-free survival. "These data suggest that tumors expressing high levels of AIB1 protein may be tamoxifen resistant," the authors write.

Moreover, patients who received adjuvant tamoxifen therapy and had both high HER-2 expression and high AIB1 expression had much worse disease-free survival than all other patient groups combined.

These results suggest that the level of AIB1 expression in the tumor may be an important predictive marker for tamoxifen resistance in clinical breast cancer, the authors write. "Our data also suggest that high levels of AIB1 must be present for the tamoxifen resistance associated with high HER-2 expression to be clinically manifest," they add.

However, they note that the patients in the study were not randomized, and that the results need to be validated by additional studies.

In an accompanying editorial, V. Craig Jordan, Ph.D., D.Sc., of Northwestern University Medical School and the Robert H. Lurie Comprehensive Cancer Center in Chicago, points out that tamoxifen is not effective in all estrogen receptor-positive breast cancers.

He says that it is important to find out whether tumors with high AIB1 and HER-2 expression that do not respond to tamoxifen might respond to an aromatase inhibitor such as anastrozole, which is currently being compared to tamoxifen in the Arimidex and Tamoxifen Alone or in Combination (ATAC) adjuvant trial.

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