Estrogen is a hormone that in females has many functions. We still do not have a complete understanding of the relationship between estrogen, estrogen-like compounds (which can bind to an estrogen receptor), and cancer.
Several factors complicate these relationships. First, there are estrogen receptors all over the body, and there are at least two types of estrogen receptors, alpha and beta. These different receptor types are distributed differently in the body, and activate different genes, sometimes in opposition to each other (Palmieri et al., 2002).
When a compound binds with an estrogen receptor, it has different effects depending on the part of the body that the receptor is in. Non-estrogen compounds such as tamoxifen may mimic estrogen in their actions in some body parts, while acting as an estrogen blocker in others. In fact, when tamoxifen was first introduced, it was believed it would be an estrogen blocker across all receptors, when in fact it blocked estrogenic effects in cancer cells, and mimicked them in bone cells (thus helping to prevent bone loss in women taking the drug for its anti-cancer properties).
The association of estrogen with breast and endometrial cancer (McGuire, 1973) makes sense because the action of estrogen in several contexts is to cause the proliferation of cells, in the breast or uterus. Every menstrual cycle, cells in the breasts and uterus proliferate, and then die off if a pregnancy does not occur, because estrogen levels drop. Over time, our cells acquire mutations, for many reasons. The problem for women is that the more menstrual cycles there are, the more chances that a cancer-causing mutation exists in a few of the cells, and that estrogen will stimulate them to proliferate out of control (Henderson et al, 1988).
One of the reasons that using birth control pills increases cancer risk is that the pills were designed to mimic “natural” cycles in women, even though there is no known physiological requirement for women to bleed as often as every month. This causes a high cumulative number of cycles for women who take the pill for years (plus they have more cycles because they have not had any pregnancies). Having a late first pregnancy (over age 30) is also a slight risk factor for breast cancer even above having no children at all, because not only has there been a lot of time and menstrual cycles for mutations to accumulate, but following mutation with long term exposure to estrogen during pregnancy can then cause those mutated cells to proliferate. (All breast lumps should be investigated, but if a lump appears in the breast of an older mother soon after giving birth, it should be considered doubly suspicious.)
But, as it turns out, estrogen mediates lung cancer in too: lung cancer is twice as prevalent in female smokers as it is in male smokers (Dougherty et al., 2006), twice as prevalent in female nonsmokers as in male nonsmokers (Wakelee et al., 2007) and estrogen stimulates tumor progression in females with lung cancer (Hammoud et al., 2008).
Because as yet not enough is understood about how the different types of estrogen receptors mediate gene activation both normally and in cancer cells, we also know little about the mechanisms of phytoestrogens, despite ubiquitous claims of both benefit and harm (Rice and Whitehead, 2006).
Phytoestrogens are compounds in plants that can bind with estrogen receptors. They occur throughout the plant kingdom, but are especially highly concentrated in flax and soy. There have been debates for years about whether phytoestrogens are protective against breast cancer or promote it, or whether they could spark a breast cancer recurrence through estrogenic activity. Because non-estrogen compounds that bind with estrogen receptors may have either estrogenic or estrogen-blocking activity, and the mechanisms of phytoestrogen effects are still not well understood, these questions have not been answered definitively.
See next: a discussion of recent research on phytoestrogens and soy diets which provides another piece to the puzzle of the role of estrogen-like compounds in cancer risk and prognosis.
Dougherty SM, Mazhawidza W, Bohn AR, Robinson KA, Mattingly KA, Blankenship KA, Huff MO, McGregor WG, Klinge CM. Gender difference in the activity but not expression of estrogen receptors alpha and beta in human lung adenocarcinoma cells. Endocr Relat Cancer. 2006 Mar;13(1):113-34.
Hammoud Z, Tan B, Badve S, Bigsby RM. Estrogen promotes tumor progression in a genetically defined mouse model of lung adenocarcinoma. Endocr Relat Cancer. 2008 Jun;15(2):475-83.
Henderson BE, Ross R, Bernstein L. Estrogens as a cause of human cancer: the Richard and Hinda Rosenthal Foundation award lecture. Cancer Res. 1988 Jan 15;48(2):246-53.
McGuire WL.Estrogen receptors in human breast cancer. J Clin Invest. 1973 Jan;52(1):73-7.
Palmieri C, Cheng GJ, Saji S, Zelada-Hedman M, Wärri A, Weihua Z, Van Noorden S, Wahlstrom T, Coombes RC, Warner M, Gustafsson JA. Estrogen receptor beta in breast cancer. Endocr Relat Cancer. 2002 Mar;9(1):1-13.
Rice S, Whitehead SA. Phytoestrogens and breast cancer–promoters or protectors?Endocr Relat Cancer. 2006 Dec;13(4):995-1015.
Wakelee HA, Chang ET, Gomez SL, Keegan TH, Feskanich D, Clarke CA, Holmberg L, Yong LC, Kolonel LN, Gould MK, West DW. Lung cancer incidence in never smokers. J Clin Oncol. 2007 Feb 10;25(5):472-8.