Antiestrogens. National Cancer Institute
 

<table border="0" cellpadding="0" cellspacing="0" width="100%"><tbody><tr><td align="left" nowrap="nowrap" valign="center">Slide 13

</td><td>http://www.cancer.gov/images/spacer.gif</td><td align="left" height="100%" valign="center" width="1">http://www.cancer.gov/images/red-px.gif</td><td>http://www.cancer.gov/images/spacer.gif</td><td align="left" valign="center" width="100%">Antiestrogens

</td><td class="pptRightNav" align="right" valign="center"> http://www.cancer.gov/images/UC-leftarrow.gif<img alt="Next Section >" src="http://www.cancer.gov/images/UC-rightarrow.gif" border="0"></td></tr></tbody></table>Since estrogen can promote the development of cancer in the breast and uterus, it seems logical to postulate that substances that block the action of estrogen might be helpful in preventing or treating these two types of cancer.
This rationale has led scientists to work on the development of “antiestrogen” drugs that can block the action of estrogens and thereby interfere with, or even prevent, the proliferation of breast and uterine cancer cells. Antiestrogens work by binding to estrogen receptors so that the estrogen molecules themselves cannot bind to those receptors. This also blocks estrogen from activating genes for specific growth-promoting proteins.
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Re: Antiestrogens. National Cancer Institute
 

<table border="0" cellpadding="0" cellspacing="0" width="100%"><tbody><tr><td align="left" nowrap="nowrap" valign="center">Slide 14

</td><td>http://www.cancer.gov/images/spacer.gif</td><td align="left" height="100%" valign="center" width="1">http://www.cancer.gov/images/red-px.gif</td><td>http://www.cancer.gov/images/spacer.gif</td><td align="left" valign="center" width="100%">SERMS

</td><td class="pptRightNav" align="right" valign="center"> http://www.cancer.gov/images/UC-leftarrow.gif<img alt="Next Section >" src="http://www.cancer.gov/images/UC-rightarrow.gif" border="0"></td></tr></tbody></table>In working on the development of antiestrogens, scientists have made a somewhat surprising discovery. Some drugs that block the action of estrogen in certain tissues actually can mimic the action of estrogen in other tissues.
Such selectivity is made possible by the fact that the estrogen receptors of different target tissues vary in chemical structure. These differences allow estrogen-like drugs to interact in different ways with the estrogen receptors of different tissues. Such drugs are called selective estrogen receptor modulators, or SERMs, because they selectively stimulate or inhibit the estrogen receptors of different target tissues. For example, a SERM might inhibit the estrogen receptor found in breast cells but activate the estrogen receptor present in uterine endometrial cells. A SERM of this type would inhibit cell proliferation in breast cells, but stimulate the proliferation of uterine endometrial cells.
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Re: Antiestrogens. National Cancer Institute
 

<table border="0" cellpadding="0" cellspacing="0" width="100%"><tbody><tr><td align="left" nowrap="nowrap" valign="center">Slide 15

</td><td>http://www.cancer.gov/images/spacer.gif</td><td align="left" height="100%" valign="center" width="1">http://www.cancer.gov/images/red-px.gif</td><td>http://www.cancer.gov/images/spacer.gif</td><td align="left" valign="center" width="100%">Tamoxifen and Cancer

</td><td class="pptRightNav" align="right" valign="center"> http://www.cancer.gov/images/UC-leftarrow.gif<img alt="Next Section >" src="http://www.cancer.gov/images/UC-rightarrow.gif" border="0"></td></tr></tbody></table>The first SERM to be investigated extensively for its anticancer properties is a drug called tamoxifen (Nolvadex®).
Tamoxifen blocks the action of estrogen in breast tissue by binding to the estrogen receptors of breast cells, thereby preventing estrogen molecules from binding to these receptors. But unlike what occurs when estrogen binds to its receptor, tamoxifen binds but does not change the receptor’s shape, so coactivators are unable to bind. As a result, the genes that stimulate cell proliferation cannot be activated.
By interfering with estrogen receptors in this way, tamoxifen blocks the ability of estrogen to stimulate the proliferation of breast cells.
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Re: Antiestrogens. National Cancer Institute
 

<table border="0" cellpadding="0" cellspacing="0" width="100%"><tbody><tr><td align="left" nowrap="nowrap" valign="center">Slide 16

</td><td>http://www.cancer.gov/images/spacer.gif</td><td align="left" height="100%" valign="center" width="1">http://www.cancer.gov/images/red-px.gif</td><td>http://www.cancer.gov/images/spacer.gif</td><td align="left" valign="center" width="100%">Tamoxifen and Breast Cancer Treatment

</td><td class="pptRightNav" align="right" valign="center"> http://www.cancer.gov/images/UC-leftarrow.gif<img alt="Next Section >" src="http://www.cancer.gov/images/UC-rightarrow.gif" border="0"></td></tr></tbody></table>In women who have breast cancer, proliferation of the breast cancer cells is often driven by estrogen, just as in the case of normal breast cells.
Since tamoxifen (Nolvadex®) can block the effects of estrogen on breast cells, scientists predicted that breast cancer could be treated by using tamoxifen to interfere with estrogen-induced cell proliferation. Based on encouraging results obtained in experimental trials, tamoxifen was first approved for such use in breast cancer treatment in the 1970s.
The first step in treating women with breast cancer is to surgically remove the cancer from the breast. It is difficult to be certain that every cancer cell has been removed at the time of surgery because some breast cancer cells could have spread to surrounding tissues or other organs prior to the operation. Therefore, women often receive some type of treatment after surgery (adjuvant therapy) to prevent the growth of any cancer cells that might remain in the body. Studies show that when tamoxifen is used for this purpose, the risk of cancer recurrence is reduced.
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