Why Raloxifene and Tamoxifen may Reduce Breast Cancer Risk (My Interpretation of the Results of STAR (Study of Tamoxifen and Raloxifene) 0f 2006)
Copyright 2006, James Michael Howard, Fayetteville, Arkansas, U.S.A.
It is my hypothesis that low DHEA may trigger breast cancer (Annals of Internal Medicine 2005; 142: 471-472). I think all tissues depend on DHEA so low DHEA causes changes in “vulnerable” cells. This effect depends upon two cellular changes. I think low DHEA initiates reductions in support of genes of cell adhesion within “precancerous” cells which ultimately separates these cells. That is, the overall, low DHEA reduces support of cell maintenance and the differentiated state. Once separated from the surrounding cellular (tissue) milieu, these cells exhibit increased cell surface area which increases their ability to absorb DHEA more rapidly than surrounding cells. So, even in a low state of DHEA, these cells may increase their supply of DHEA. I suggest this causes a sub fraction of the cells already separated from the others to trigger genes of growth because of the increased DHEA. (According to my explanation of growth and development, the large amounts of DHEA early in development stimulate cell divisions. This produces a cell mass. The size of the cell mass and the reduced cell surface area contribute to differential availability of DHEA so activation of genes increases while cell duplication decreases. As DHEA availability decreases, the ratio of cell differentiation to cell division decreases.) When these cells experience an increase in DHEA because of increased absorption, their genes of cell division are activated. These are “oncogenes.” Conversely, as we age, our DHEA begins to naturally decline, reaching very low levels in old age. This is why cancer increases in old age, but it grows less rapidly.
It is also my hypothesis that all tissues rely on DHEA for optimal DNA transcription and replication. All tissues compete for available DHEA; this effect may produce differentiation of tissues (above) as well as affect the entire body plan. So, once initiated, cancer absorbs DHEA at the expense of other tissues. (I suggest this is the cause of “cachexia” of cancer, that is, the cancer robs the body of available DHEA and is very noticeable in cancer of old age when DHEA is low.) My point here is that, once initiated, cancer relies on an increased source of DHEA. If available DHEA can be reduced, cancer will be adversely affected because cancer relies on DHEA more than differentiated tissues. I think many anticancer chemotherapeutics work by reducing available DHEA. This may explain why chemotherapy is so damaging; reducing DHEA affects all tissues. Hopefully, the cancer dies before other tissues, which rely on less DHEA. (Because cancer uses DHEA at the expense of other tissues, cancer reduces overall DHEA. Therefore, my explanation of cancer and low DHEA also explains why some cancers stimulate the onset of different kinds of cancer. When cancer reduces DHEA, it can cause the initiation of other cancers by reducing DHEA. Also, since some chemotherapy, and other anticancer therapies, may reduce DHEA, I suggest this is why some of these treatments have also been demonstrated to cause other types of cancers.)
I think raloxifene and tamoxifen work by reducing DHEA. Both raloxifene and tamoxifen reduce prolactin. Prolactin is a direct stimulator of DHEA production; if one reduces prolactin, one reduces DHEA. Raloxifene and tamoxifen do not affect prolactin identically, so one would expect differences. The STAR report found that both reduced the risk of invasive breast cancer by approximately 50%. If breast cancer is started by low DHEA and depends on DHEA once formed, then reducing prolactin should reduce the ability of the cancer to function. These two chemicals both reduce the extension of cancer.
It is also my hypothesis that low DHEA may increase blood clots (http://members.cox.net/jmhoward3/Thrombosis%20May%20Be%20Caused%20by%20Low%20DHEA.htm ). Both tamoxifen and raloxifene increase blood clots. Obviously, I think this effect is due to reduction of DHEA by both. Since raloxifene and tamoxifen exert effects differently, the results should differ. Raloxifene simply affects the levels of DHEA differently than tamoxifen.