That’s right! Estrogen, one of the primary female sex hormones, protects breast cancer cells from our immune system. How ironic is that? One part of our body functions to protect while the other wants to destroy the same. I can’t think of other opposing reactions such as these but I am absolutely certain that there are a huge number of such antagonistic reactions present in our body.

Tamoxifen is a drug used to treat breast cancer. How does this drug function? Hormones normally function by binding to a receptor that will cause a series of reactions to occur and result in some kind of change in the system. Estrogen works in the same way and it needs to bind to an estrogen receptor to produce any kind of change. Our smart drug, tamoxifen, saves the day by binding to this estrogen receptor thereby blocking estrogen from doing the same. Smart drug, indeed!

But, what happens when estrogen binds to the estrogen receptor? This part is for the geeks, but I think it is super cool. Shapiro and colleagues (Jan, 2007) explained the techniques used by our protective soldier, estrogen. In the absense of our smart drug, estrogen binds to the estrogen receptor which will induce the expression of a newly discovered gene proteinase inhibitor-9 or PI-9. So, as soon as estrogen binds to it’s receptor, it leads to the production of PI-9 protein. (Gene is part of the DNA. It is transcribed and translated to form the protein.) 
What does PI-9 do? It binds to granzyme B which is a primary protease (a cell filled with a solution that acts like poison to kill cells) used by natural killer (NK) cells. This protease enzyme of natural killer cells, as the name indicates, is responsible for destroying infected or transformed cells. Here is an image of how this reaction looks like.
 

Cancer cells are transformed cells. They have a kind of glitch in the cell division machinery that causes excessive growth of cells - hence forming the tumor. Even a little bit of estrogen is enough to promote the production of PI-9 protein. In the current paper, M. Nathaniel Mead proposed compared the concentration levels of estrogen, estrogen receptor and PI-9 and linked increasing concentration of estrogen with increasing concentrations of PI-9 and increasing blocks in cell deaths due to NK. He also noted that estrogen receptors are increasingly present in women with breast cancer. This is also an indication of the presence of tamoxifen. Thus, the presence of either tamoxifen or estrogen can promote the production of PI-9.
Tamoxifen is an incredible drug. It has different outcomes depending on the concentration of drug used. If it’s used in small amounts it will protect the breast cancer cells by increasing the estrogen receptors and promoting production of PI-9. In large amounts it will destroy this and other kinds of estrogen responsive cancers. Most breast cancer cells have low or moderate levels of estrogen receptors present. Knowing this it should be clear that only in a very small number of cases, where these cells contain a lot of estrogen receptors, tamoxifen will protect these cells.

What about environmental products that contain estrogen? Can they have any affect on the progression of breast cancer? YES! DDT is one of these products and increasing the amount of exposure to environmental estrogen will also protect the cancer cells from the immune system’s natural killer cells. These forms of estrogen also don’t have an affect on breast cancer cells in small amounts but when mixed with other environmental estrogen forms may have a significant affect.

What did they learn from this study? If they can block the production of PI-9, which blocks the function of the natural killer cells, they can significantly remove the protection given to breast cancer cells through estrogen. Another cancer therapy in progress!

(Note: this study was published in June 2007. There may have been significant research done on this since then and I will post about it as soon as I find it. Stay tuned!)