Tamoxifen is a mainstay of breast cancer treatments: it blocks the effects of the female hormone estrogen on the breast, inhibiting estrogen’s tendency to encourage breast tissue to grow uncontrollably. Now, Dr. Seema Khan, professor of surgery at Northwestern University Feinberg School of Medicine, reports in Clinical Cancer Research that putting the drug in a gel, and applying it directly to the breast tissue, where it needs to work, may have merit.
Doctors generally prescribe tamoxifen for women diagnosed with early breast cancer, including very early-stage ductal carcinoma in situ (DCIS), to prevent recurrent growths. But the drug has also been linked to an increased risk of stroke, blood clots and cancers in other tissues, including the uterus. That’s why more women, including those who have not yet had cancer but are at high risk for the disease could benefit from the drug but are reluctant to take it.
Dr. Khan’s study was small—only 26 women—but it provides proof that the principle of applying tamoxifen directly on the breast may be worth investigating. All of the women were diagnosed with DCIS, which generally does not spread. But 30% of DCIS can recur even after surgery and proper treatment, so most women are prescribed tamoxifen. In the current study, about half of the women in the study were randomly assigned to take the oral form of the drug, while the other half were given doses of a tamoxifen gel to apply directly to the breast tissue for six to 10 weeks before their surgery. Khan analyzed the breast tissue after surgery to study markers for tumor growth, and conducted blood tests for levels of tamoxifen metabolites as well.
At the end of the study, the women in both groups showed similar decreases in tumor-related proteins, but blood levels of tamoxifen were five times lower among the women using the gel than those taking the oral pill. That, says Dr. Khan, suggests that the major side effects of the drug, which occur in the blood and other reproductive organs, may be largely avoided if women use the gel.
“Our study showed that applying the drug through the breast skin leads to high concentrations in the breast and low concentrations in the rest of the body,” she says. “The biological effect on the breast is consistent with the benefit of oral tamoxifen, so for that reason, we hope that this kind of approach would make preventive medication more acceptable to women with non-invasive breast cancer and how may be at high risk of developing breast cancer.”
Dr. Khan says that the breast may be uniquely designed for such transdermal therapy, since it is essentially an appendage of the skin, with its own internal lymphatic circulation. That may keep things applied to the breast skin within the breast tissue, and could explain the higher concentrations of tamoxifen metabolites she and her team found after the gel applications.
Still, she says that the small number of participants in the study means more research is needed to confirm the results. Right now, the gel version is not available. The company that provided the experimental doses for the study stopped making that formulation, so Dr. Khan is studying a related, similar metabolite called endoxifen that may have similar cancer-fighting effects on breast tissue.
If the strategy proves effective, it’s possible that cancer treatments, or at least breast cancer treatments, may become useful in preventing cancer as well, as more women at high risk who have yet to be diagnosed with the disease take advantage of them. Applying a gel with relatively few side effects may help more women to eliminate small tumors before they have a chance to grow. And if other types of drugs can be used on the skin as well, that could significantly broaden the therapies available to women looking for ways to prevent the disease.
“For high-risk women who need better prevention strategies, delivering the drug to the breast is a very desirable solution,” says Dr. Khan.
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