Using estrogen to combat persistent breast cancer

In some breast cancer patients who have tried everything but 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 in the breast often multiply when estrogen binds to receptor proteins on the cells. But the hormone’s effects on a tumor are far from one-dimensional. Estrogen can also send breast cancer cells into a spiral of programmed death. If dying cells outnumber multiplying cells, tumor growth stalls.

Indeed, synthetic estrogen was used as a treatment option for breast cancer for decades until the drug tamoxifen gained approval more than 25 years ago. Tamoxifen starves breast cells of estrogen by binding to the estrogen receptors on cells, as does a newer drug called fulvestrant. Other drugs, known as aromatase inhibitors, prevent estrogen manufacture by the body.

Combined, these drugs have provided breast cancer patients with an array of hormone-deprivation therapies that can have fewer side effects than estrogen therapy, can keep the cancer at bay and are more tolerable than chemotherapy. Even so, roughly 40,000 women die of breast cancer in the United States each year, most of them with estrogen-receptor-positive tumors that become insensitive to these estrogen-deprivation treatments, says study coauthor Matthew Ellis, an oncologist and molecular biologist at 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 seven years, on average. Half of the women got a high dose of estrogen and the others a low dose. The high-dose recipients averaged age 60, and the low-dose group averaged age 55.

After 24 weeks, tumors had stopped growing or had shrunk in nearly one-third of volunteers in both groups. That suggests that the cancerous cells had reorganized themselves in these women after years of estrogen deprivation and had become susceptible to the cell death effects of estrogen, 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 estrogen therapy, each woman was injected with a dose of glucose containing a labeling compound that could be traced in the body by a combined positron emission tomography and CT imaging scan an hour later. In some women, the tumors glowed on the scan. After the 24 weeks of treatment, 80 percent of women who had shown the “flare” on the scan benefited from the estrogen treatment.

“The glucose flare monitor, I think, is quite exciting,” says Richard Santen, a clinical endocrinologist at the University of Virginia in Charlottesville. “It’s a good way to predict who would respond to this endocrine therapy.”

It remains less clear how long estrogen’s benefit would last. “But it could buy time,” Santen says.

A larger study investigating the low-dose estrogen option is under consideration, Ellis says.