Estrogen: A Villain And A Possible Savior

By Shannon Brownlee

There is no single cause for breast cancer, but one major factor is estrogen. That's a shocking thought. The same hormone that softens our skin, thickens our hair and fills out our hips and breasts also feeds disfiguring tumors. Rates of breast cancer are highest in developed nations, in part, scientists believe, because with better nutrition we reach menses earlier and menopause later, allowing estrogen to course through our bodies for that much longer.

If there is a bright side to all this, it is that estrogen is now pointing the way to new breast-cancer treatments. One of the most exciting developments in the field is a new class of drugs called aromatase inhibitors, which for postmenopausal women are already in use against late-stage tumors and may prove even more effective when tumors are caught early. Aromatase inhibitors block the action of an enzyme that these women need to produce estrogen. Two new studies suggest that the drugs can shrink tumors before surgery and also perhaps prevent breast cancer from recurring. More than 20,000 women are enrolled in clinical trials designed to show just how effective the aromatase inhibitors are in early cancer and how best to use them.

These drugs could one day replace tamoxifen, which is routinely given to women at high risk for recurring tumors, and raloxifene, a newer drug that was originally designed to prevent osteoporosis but also appears to block breast cancer. Known as "designer estrogens," tamoxifen and raloxifene work by taking the place of the body's natural estrogen on the surface of breast-cancer cells, preventing the real thing from stimulating tumor growth.

Five years ago, doctors and their patients hailed tamoxifen, which was the first drug approved for reducing the risk of getting breast cancer (rather than just treating it). But tamoxifen is far from perfect. It increases the risk of uterine cancer and potentially fatal blood clots. Raloxifene appears to provoke fewer side effects, but the results from a head-to-head study comparing the two drugs won't be available until 2009.

Meanwhile, researchers are getting better at predicting who is most likely to benefit from which designer estrogen. Raloxifene, it turns out, is most effective for the postmenopausal women who have naturally high levels of estrogen. Other tests suggest that tamoxifen offers little or no benefit to women who carry the BRCA1 mutation, one of two genetic mutations known to cause an inherited form of breast cancer, but it can help lower the risk of breast cancer in women carrying a variation of the gene called BRCA2. For now, women who are taking tamoxifen should continue doing so. But in the future, doctors will almost certainly have more drugs to choose from. They may, for example, use designer estrogens and aromatase inhibitors in sequence to try to keep breast cancer cells off-balance.

The ultimate goal, of course, is to keep breast cancer from taking hold in the first place, and estrogen will play a role in achieving that. One idea that researchers have begun to test is temporarily suppressing the body's natural estrogen and thus providing birth control along with protection from breast cancer. This could be accomplished by combining an ovulation-stopping drug with tiny doses of female hormones to protect tissues like bone and brain. A pilot study conducted at the University of Southern California in women with a family history of breast cancer showed that such a dosage regimen reduced breast density, making mammograms easier to read. An added benefit: the treatment cut their menstrual cycles to three a year.

--By Shannon Brownlee. Reported by Sora Song/New York

With reporting by Sora Song/New York