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