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While the drug tamoxifen can be very effective at
helping to treat breast cancer, researchers know that tamoxifen does not work well in all
patients. Previous research has shown that women with certain types of breast cancer,
specifically those that are not estrogen sensitive, do not typically benefit from
tamoxifen. Now, researchers have uncovered more information about tamoxifen. In a recently
published study, Baylor College researchers report that certain proteins seem to
"deactivate" the positive effect of tamoxifen in some women whose cancers are
estrogen sensitive. The research may lead to more effective treatments that target
these proteins.
Tamoxifen is a drug taken orally in pill form. For over twenty years, physicians have
prescribed tamoxifen to help treat patients with advanced breast cancer. More recently,
tamoxifen has been used as to treat early stage breast cancer after surgery. Tamoxifen has
been shown to help prevent the original breast cancer from returning after breast surgery
while also hindering the development of new cancers in the opposite breast.
Approximately 80% of women who are diagnosed with breast cancer have estrogen-receptor
positive breast cancers (also called estrogen sensitive cancers). That is, their breast
cancer cells contain estrogen receptors. Tamoxifen fights estrogen sensitive cancers
particularly well because the drug binds to the estrogen receptors, preventing estrogen
from reaching the cancer cells. Because these cancer cells depend on estrogen for
survival, a lack of estrogen starves them. While tamoxifen works well in estrogen-receptor
positive breast cancers, it is typically less beneficial in women with estrogen-receptor
negative breast cancers (i.e., cancers that do not contain estrogen receptors).
Researchers have been focused on trying to discover why this is the case. For the
meantime, women with estrogen-receptor negative breast cancer do not typically receive
tamoxifen.
Yet tamoxifen does not work well in all women with estrogen-receptor positive breast
cancers either. To determine whether certain levels of proteins present within breast
cancer cells can affect the performance of tamoxifen, Dr. C. Kent Osborne and colleagues
from Baylor College of Medicine studied breast cancer tumors of 316 women who all had been
diagnosed with estrogen-receptor positive breast cancers. In particular, they searched for
two proteins, HER2 and AIB1 (also called SRC-3).
Researchers have previously found that women whose breast cancers contain an
overabundance of HER2 proteins tend to have aggressive diseases. This research has led to
the development of a promising drug, Herceptin, to
help treat cancers that contain too many HER2 proteins. Some research has shown that
cancers with high levels of HER2 may be resistant to tamoxifen, but data are mixed.
When Dr. Osborne and colleagues analyzed the breast cancer tumors in their study, they
found that those cancers with high levels of both HER2 and the AIB1 proteins tended to
respond poorly to treatment with tamoxifen, suggesting that the proteins interfere with
the drug’s activity. In fact, women who had high AIB1 levels and did not receive
tamoxifen fared better (survived for longer periods of time and remained cancer free for
longer intervals) than those women with high AIB1 levels who took tamoxifen.
The research suggests that determining AIB1 levels in breast cancer patients is
important in predicting which patients will respond well to tamoxifen and which patients
need not take the drug. Furthermore, medicines that specifically target the AIB1 protein
could be an important advance in breast cancer treatment, similar to the drug Herceptin
that targets the HER2 protein. Future studies of the AIB1 and HER2 proteins will help
researchers better understand their roles and how they might figure into the development
of new treatments.
Additional Resources and References
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