Raloxifene imparts anticancer benefit.

When the osteoporosis drug raloxifene came on the market last year, it offered women a way to strengthen their bones yet avoid the breast-cancer risk associated with estrogen-replacement therapy. Now, researchers report that raloxifene may actually prevent breast cancer in many women.

As part of a worldwide study to gauge raloxifene's effects on osteoporosis, scientists gave the drug to two-thirds of a group of 7,705 postmenopausal women with the brittle-bone disease. The other participants received an inert substance. Neither the scientists nor the study participants knew which pills contained the medication.

All participants also took calcium and vitamin D supplements daily and received regular mammograms or breast ultrasound examinations in addition to bone measurements.

During the 40-month study, 27 of the 2,576 women receiving the inert pills developed breast cancer, while only 13 of the 5,129 women taking raloxifene were diagnosed with the malignancy. In other words, breast-cancer incidence with the drug was only one-fourth as great as without it, the researchers report in the June 16 JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION.

"It's a landmark study," says Michael B. Sporn, a pharmacologist at Dartmouth Medical School in Hanover, N.H.

The drug seems to stifle invasive breast cancer, in which estrogen induces uncontrolled cell growth, says study coauthor Steven R. Cummings, an internist and epidemiologist at the University of California, San Francisco. In about two-thirds of breast cancers in postmenopausal women, the hormone fuels a tumor's growth, he says.

Estrogen circulating in the blood attaches to one of two estrogen-receptor molecules in cells. The receptors then activate specific genes, inducing a chain reaction of protein production that can lead to cell growth. Such a flurry of activity initially poses little risk, but repeated exposure to estrogen over a long period of time "is too much of a good thing," says Leo Plouffe, a research physician at Eli Lilly and Co. in Indianapolis, which makes raloxifene.

"If you consistently promote the growth of certain cells [with estrogen], the cells might transform themselves into cancer cells," he says. Or, if cancer is already present, the estrogen stimulus might abet the disease.

Raloxifene works by occupying the estrogen receptors, Cummings says. When the drug thus blocks the receptor on a cancerous cell, estrogen cannot bind and apparently the cell dies off, he says.

In its role as a bone-growth promoter, however, raloxifene mimics rather than blocks estrogen's effects. Precisely how raloxifene can play one role in one cell and another elsewhere remains unclear, Cummings says.

Raloxifene may provide yet another benefit: Women receiving the drug in this study didn't show the increased incidence of uterine cancer that previous research has associated with both estrogen and the anti-breast-cancer drug tamoxifen.