The drug tamoxifen can help prevent breast cancer in women at an increased risk of the disease. But many women who stand to benefit from tamoxifen do not take the drug—a pill—because of concerns about side effects, such as hot flashes and the increased risk of blood clots and stroke. To explore alternatives to oral tamoxifen that might have fewer side effects, researchers are testing a topical form of the drug in two clinical trials. These randomized placebo-controlled studies are evaluating a gel formulation of tamoxifen called 4-hydroxytamoxifen (4-OHT) that women apply directly to the breasts. The goal of this research is to find out if delivering a form of tamoxifen topically results in the same level of the drug in the breast but leads to lower levels of the drug in the blood and other parts of the body compared with oral delivery, according to Brandy Heckman-Stoddard, Ph.D., of NCI’s Division of Cancer Prevention. “With lower levels of the drug in the body, women would potentially have fewer side effects,” she added.