Review of Hormones and breast cancer: can we use them in ways that could reduce the risk?

Dr. Alicia Stanton – June 2009- The only hormone most people think about in relation to breast cancer is estrogen. However, many hormones affect breast cancer in positive and negative ways. Estrogen, progesterone, testosterone, DHEA, melatonin, oxytocin, insulin and T3 (tri-iodothyronine) can all affect breast cancer. Dr Mahmud’s review article does a great job of explaining these effects. Estrone and estradiol are two stronger estrogens that can stimulate breast cancer through the estrogen receptor alpha (ER-alpha) on malignant cells. Interestingly, post-menopausal women have 10 to 50 times the amount of estrogen in the tissue around their breast cells than they do in their blood. The fat cells around these breast cancer cells have an enzyme, aromatase, which actually makes more estrogen for them. Therefore, knowing the blood level of estrogen may not give you the whole story.

Dr. Mahmud discusses several studies showing that estrogen therapy does not actually cause an increase in breast cancer. As a matter of fact, studies that used bioidentical hormones actually showed a decrease in incidence (please see his paper for the references). He also points out a study in baboons where exogenously administered estrogen actually reduced the aromatase enzyme in the fat cells of the breast. Therefore, exogenous estrogen may actually protect the tissue rather than cause harm. There is also evidence that estriol, a weak estrogen, is protective against breast cancer as it binds to the ER-alpha receptor on breast cancer cells and inhibits the entry of the stronger estrogens. He suggests a transdermal combination of estriol and estradiol as the preferred choice for hormone replacement therapy. Dr. Mahmud notes that oral estrogens increase clotting factors and CRP which does not occur with transdermal preparations.

Bioidentical progesterone appears to be an anti-cancer hormone based on a number of studies which are quoted in the review article. It has been shown to up-regulate p53, a breast cancer tumor suppressor gene, and down-regulates bcl-2 and surviving, tumor promoter genes. It was noted that this effect was for bioidentical progesterone only. Provera (medroxyprogesterone acetate) showed a 40% increase in breast cancer. Testosterone has also been shown to have a direct anti-cancer effect by decreasing ER-alpha receptor activity in breast cells of monkeys. DHEA also inhibits the growth of breast cancer cells in mice and patients with low DHEA levels and breast cancer tend to have more metastases. The author noted that both testosterone and DHEA could be converted to estrogen in the body and care should be taken to monitor estrogen levels.

Other hormones mentioned include melatonin, oxytocin, insulin, tri-iodothyronine (T3) and human growth hormone (hGH). Melatonin has many anti-cancer effects and anti-inflammatory effects. It up-regulates tumor suppressor genes and reduces the concentration of ER-alpha receptors on the cancer cell. Oxytocin has anti-cancer effects including inhibiting ER-alpha receptors. Thus breastfeeding and nipple stimulation appear to be protective for breast cancer. Insulin acts as a growth factor and promotes the growth of cancer cells by increasing tyrosine kinase. Insulin resistance should be managed aggressively for this reason (among many others) as breast cancer patients with high insulin levels tend to have more metastases. Tri-iodothyronine (T3) has anti-cancer effects including increasing natural killer (NK) cell activity and interleukin-2, both have activity that inhibits cancer cells. T3 also increases sex hormone binding globulin (SHBG) which binds to estrogen and provides protection from breast cancer.The author notes that TSH and T4 do not have this effect so T3 should be monitored. Also, since Synthroid has only T4 and relies on the body to convert it to T3, it should be utilized in conjunction with a T3 compound or not used in favor of a T3/T4 combination therapy like Armour thyroid. Although hGH increases the production of an insulin-like growth factor, which can stimulate cancer cells, it has many anti-cancer effects as well. It increases the activity of NK cells, increases the level of vitamin D, inhibits the estrogen induced proliferation of cancer cells and repairs DNA damage to cells. The author suggests that, when indicated, hGH therapy should not be withheld for fear of cancer.

In summary, Dr. Mahmud states that many hormones affect breast cancer, positively or negatively. An understanding of the effects and their mechanisms can help us to use these different hormones judiciously and I ways that could potentially reduce or minimize the risk of breast cancer.

Read Khalid Mahmud's Hormones and breast cancer: can we use them in ways that could reduce the risk?