From troublemaker to treatment: study finds estrogen may fight persistent breast cancer.

In some breast cancer patients who have tried every drug treatment short of chemotherapy, estrogen can stall tumor growth, a new study finds.

The idea is counterintuitive since estrogen acts as a growth stimulant in most breast cancers. But using the hormone as an anticancer weapon is actually an old strategy that might offer a new treatment option, researchers report in the Aug. 19 Journal of the American Medical Association. They are cautiously optimistic because a screening test used in the new study can determine with considerable accuracy which breast cancer patients would probably benefit from estrogen.

Most breast cancers are estrogen-receptor positive, meaning cancer cells often multiply when estrogen binds to receptor proteins on the cells. But the hormone's effects on a tumor are not one-dimensional. Estrogen can also send cancer cells into a programmed celldeath response. If dying cells outnumber multiplying cells, tumor growth stalls.

Synthetic estrogen was used as a treatment option for breast cancer for decades until hormone-deprivation drugs, including tamoxifen, gained approval. Still, roughly 40000 women die of breast cancer in the United States each year, most of them with estrogen-receptor-positive tumors that become insensitive to estrogen-deprivation treatments, says study coauthor Matthew Ellis of Washington University School of Medicine in St. Louis.

In the new study, Ellis and his colleagues enrolled 66 breast cancer patients who had relapsed despite multiple rounds of estrogen-deprivation treatments over more than seven years, on average. Half of the women got a high dose of estrogen and the others a low dose.

After 24 weeks, tumors had stopped growing or shrunk in nearly one-third of volunteers in both groups. That suggests that the cancerous cells had reorganized themselves, becoming susceptible to estrogen's cell-death effects, Ellis says. "We don't have a handle on the precise mechanism by which that happens."

But a test used in the study can spot patients likely to benefit from estrogen, he says. One day after starting therapy, each woman was injected with a dose of glucose containing a labeling compound that could be traced in the body. In some women, the tumors glowed on a combined PET CT scan. After the 24 weeks, 80 percent of women who had shown the "flare" on the scan benefited from the treatment.

"It's a good way to predict who would respond to this endocrine therapy," says Richard Santen of the University of Virginia in Charlottesville.