Researchers Discover Why Tamoxifen is Not Effective in Some Breast Cancer Patients (dateline November 21, 2002)
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-negativethey 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. "Its 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 drugs 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:
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.