TUMOR RECURRENCE AND TAMOXIFEN RESISTANCE: IS TAMOXIFEN RESISTANCE THE SAME PROBLEM?

Typically, most patients with breast tumors that are estrogen and progesterone receptor positive will respond to tamoxifen. When they develop resistance to tamoxifen after six months to a year of therapy, the tumor will begin to recur. Fortunately, for many patients who no longer respond to tamoxifen therapy another effective hormonal agent can be found. These alternative agents usually work for a period of time not exceeding a year, after which the patient again develops resistance. Tamoxifen tends to be given as a “first-line” therapy because it has significantly fewer side effects than other hormonal agents, so the development of resistance to this drug is a significant clinical problem.
At one time it was thought that a patient who no longer responded to tamoxifen probably was not taking the drug as directed (thus not enough drug was getting into the breast tumor cells) or perhaps was eating a diet high in “phytoestrogens.” These are estrogenic compounds found in many plant products that were believed to stimulate the growth of breast cancer cells just as estrogen does. The phytoestrogens are known to be capable of diminishing the effects of the antiestrogen tamoxifen. Weight gain over a prolonged period was also suspected to contribute to the loss of tamoxifen effectiveness. Because tamoxifen is a drug that is taken up by the fat cells and often retained in fatty tissue, an increase in weight without an increase in tamoxifen dose was believed to decrease the amount of drug available to the breast tumor. Even though all these explanations are plausible, their overall contribution to tamoxifen resistance is now considered minimal. Tamoxifen resistance apparently is associated with resistant mechanisms at the level of the breast cancer cell itself.
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TUMOR RECURRENCE AND TAMOXIFEN RESISTANCE: IS TAMOXIFEN RESISTANCE THE SAME PROBLEM?Typically, most patients with breast tumors that are estrogen and progesterone receptor positive will respond to tamoxifen. When they develop resistance to tamoxifen after six months to a year of therapy, the tumor will begin to recur. Fortunately, for many patients who no longer respond to tamoxifen therapy another effective hormonal agent can be found. These alternative agents usually work for a period of time not exceeding a year, after which the patient again develops resistance. Tamoxifen tends to be given as a “first-line” therapy because it has significantly fewer side effects than other hormonal agents, so the development of resistance to this drug is a significant clinical problem.At one time it was thought that a patient who no longer responded to tamoxifen probably was not taking the drug as directed (thus not enough drug was getting into the breast tumor cells) or perhaps was eating a diet high in “phytoestrogens.” These are estrogenic compounds found in many plant products that were believed to stimulate the growth of breast cancer cells just as estrogen does. The phytoestrogens are known to be capable of diminishing the effects of the antiestrogen tamoxifen. Weight gain over a prolonged period was also suspected to contribute to the loss of tamoxifen effectiveness. Because tamoxifen is a drug that is taken up by the fat cells and often retained in fatty tissue, an increase in weight without an increase in tamoxifen dose was believed to decrease the amount of drug available to the breast tumor. Even though all these explanations are plausible, their overall contribution to tamoxifen resistance is now considered minimal. Tamoxifen resistance apparently is associated with resistant mechanisms at the level of the breast cancer cell itself.*42\320\2*

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