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Minute quantities of estrogen act as an apoptotic trigger in breast cancer cells resistant to estrogen deprivation
The ubiquitous use of antihormonal therapy raises the important issue of the development of drug resistance. Laboratory studies indicate that long-term (5-10 years) of tamoxifen treatment or long-term estrogen deprivation initially results in the control of breast cancer cell growth but eventually drug resistant cells emerge because survival mechanisms are enhanced and apoptosis is suppressed. Nevertheless, the studies on the development of drug resistance to long-term antihormonal therapy have revealed a vulnerability that can be exploited for the treatment of breast cancer. Although estrogen is considered to be a survival mechanism that enhances breast cancer cell growth and replication, minute quantities of estrogen now act as an apoptotic trigger following the development of drug resistance through long-term antihormonal treatment. Laboratory studies demonstrate that this process of apoptosis is rapid and triggered by a mitochondrial mechanism that could be exploited through clinical studies in the future. It is well known that high dose estrogen treatment (15 mg DES per day) can be used to treat breast cancer. This was the standard of care for advanced breast cancer 35 years ago before the development of tamoxifen. The question now arises of whether a minimum dose of estrogen can be determined through clinical trials but could now be used for short periods to reverse drug resistance to antihormones and enhance the continuing use of valuable therapeutic agents in breast cancer.
Bibliographical reference:
V. Craig Jordan, Fox Chase Cancer Center, Philadelphia, PA
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