Tamoxifen and Breast Cancer

 
When you get to my age, more and more of your female relatives, friends, and acquaintances will be diagnosed with breast cancer. They will be undergoing more or less radical surgery followed by chemotherapy and/or drug treatment. One of the most common drugs for the treatment of breast cancer is tamoxifen.

Tamoxifen is a chemical that binds to a protein called estrogen (or estradiol) receptor. The estrogen receptor is a protein that binds to DNA to increase (activate) or decrease (repress) gene expression. Its DNA binding properties are influenced by its interaction with the hormone estradiol (estrogen)—a discovery first reported by my friend Keith Yamamoto back in 1972 (Yamamoto and Alberts, 1972).

In normal cells, estrogen can stimulate the growth of tissues by turning on the genes that promote cell division. This is a good thing. However, it turns out that most of the breast cell cancers arise from cells that have estradiol receptors and in that case the presence of estrogen in your blood stream makes the cancer cells grow. These forms of cancer are called estrogen receptor positive (ER+) breast cancers.

That's the bad news. The good news is that such cancers respond well to tamoxifen. The effectiveness of tamoxifen is due to the fact that it binds to the estradiol receptor but doesn't convert it to the active regulator of gene expression.¹ When you take tamoxifen there's so much more of it in your bloodstream that it out-competes all of the estrogen. As a result the cancer cells can't grow, (but neither can any of the other tissues that need estrogen).

Hormone therapy (tamoxifen) is often combined with radiation or chemotherapy to reduce the risk of recurring cancer for women who have undergone surgery to remove tumors. However, if the cancer has not spread to the lymph nodes then hormone therapy by itself is effective against ER+ breast cancer. This is especially true for pre-menopausal women 40 years of age or older where chemotherapy does not add significantly to the effectiveness of tamoxifen [see tamoxifen].

---

1. This isn't quite true. Tamoxifen itself doesn't bind to the estradiol receptor protein, instead it is converted inside your body to other chemicals that do bind.

Yamamoto KR, Alberts BM. 1972 In vitro conversion of estradiol-receptor protein to its nuclear form: dependence on hormone and DNA. Proc. Natl. Acad. Sci. USA. 69:2105-2109. [PubMed]