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Tamoxifen is the most commonly used drug to help
treat breast cancer in women with early and advanced stages of the disease. The treatment
works by blocking estrogen from reaching breast cancer cells that depend on the hormone
for survival. However, tamoxifen does not work in all women, and some patients become
resistant to the drug. Now, researchers have discovered a chemical switch that contributes
to these effects. The research may help physicians determine which women would and would
not benefit from tamoxifen before even beginning treatment.
Many breast cancer cells contain estrogen receptors. These cancer cells depend on the
hormone estrogen in order to grow and multiple. When estrogen reaches breast cancer cells,
it binds to these estrogen receptors and feeds the cells. Tamoxifen is designed to block
estrogen from reaching these receptors, thereby "starving" the cancer cells.
Approximately 80% of breast cancers are estrogen receptor-positive; that is, they contain
estrogen receptors. The remaining 20% are estrogen receptor-negative—they do not
contain estrogen receptors. Those women with estrogen receptor-positive breast cancers are
typically candidates for tamoxifen.
Though tamoxifen can be highly effective at treating breast cancer, it does not always
work in women whose breast cancer cells contain estrogen receptors. The British charity
organization Cancer Research UK estimates that 70% of women with estrogen
receptor-positive breast cancers respond to tamoxifen treatment. Others do not respond or
become resistant to tamoxifen.
A study published in a recent issue of the journal Oncogene helps explain why
tamoxifen does not work in some breast cancer patients. Dr. Simak Ali of Imperial College
in London and his colleagues studied the estrogen receptor molecule (MAP kinase) in breast
cancer cells to determine whether it was the same as the molecule found in healthy breast
cells. They found that the molecule became chemically altered in some breast cancer
patients. This finding is significant because when the molecule is changed, the cancer
cells actually thrive on tamoxifen instead of being weakened by the drug.
"Chemical alteration seems to switch the [estrogen receptor] molecule into a
completely different state, in which it becomes immune to the inhibitory effects of
tamoxifen," explained Dr. Ali, in a Cancer Research UK news release about the study.
"It’s important that we learn to identify women who are not going to respond to
the drug, so we can spare them from unsuccessful treatment and explore other ways of
looking after them."
Saving women from unnecessary treatment with tamoxifen would also spare these women
from some of the drug’s potential side effects. Though most women can tolerate
tamoxifen, the most common side effects include hot flashes, irregular menstrual cycles,
unusual vaginal discharge or bleeding, and irritation of skin around vagina.
Tamoxifen also increases a woman's chances of developing serious health problems
including:
- endometrial cancer (cancer of the lining of the uterus)
- deep vein thrombosis (blood clots in large veins, particularly in the legs)
- pulmonary embolism (blood clot in the lung)
- possibly stroke
Dr. Ali and his colleagues hope to develop a test that can be administered to breast
cancer patients to determine whether they would benefit from treatment with tamoxifen
before they ever take the pill. This would save many women from costly therapy that does
not work while also identifying which women would reap that greatest benefit from the
drug.
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