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Pregnancy-hormone therapy blocks cancer.

If pregnancies early in adulthood reduce a woman's lifelong risk of developing breast cancer, could short-term hormonal treatments that simulate aspects of pregnancy do the same thing? A new study on rats suggests that the answer is yes.

This finding fuels hope that scientists can develop a means to reduce women's risk of breast cancer. Among malignancies in women, it's the second-leading cause of death.

Satyabrata Nandi of the University of California, Berkeley and his coworkers administered a potent carcinogen to 7-week-old female rats, a common procedure used to study cancer risk. Two weeks later, they treated each animal with one of several agents that cause a maturation, or differentiation, of breast structures known as terminal end buds.

The agents mimic changes during pregnancy when those end buds transform into milk-producing lobules. Untransformed buds are believed to be especially vulnerable to carcinogens (SN: 8/5/95, p. 92).

In one experiment, the researchers stimulated the lobule development with an injection of the drug perphenazine. In others, they implanted capsules that dispensed the hormones estrogen, progesterone, or both in a range of doses for 3 weeks--the gestation period of these animals. The implants increased blood hormone concentrations to those that occur in various phases of pregnancy.

In groups of rats getting no treatment, 90 to 100 percent of the carcinogen-exposed animals developed breast cancer within 9 months. The big surprise, Nandi's group reports in the March 2 PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES, is that despite triggering a similar maturation of the end buds, the drug and hormones offered vastly different levels of protection.

Perphenazine cut the 9-month cancer incidence to just under 75 percent, while breast-cancer rates in animals receiving the pair of hormones plummeted to between 4 and 11 percent. "What that told us," Nandi says, "is that [end-bud] differentiation is probably not the reason for protection against breast cancer following pregnancy." This had been the leading hypothesis.

The hormonal duo proved effective even when delivered several weeks before the carcinogen exposure. It also worked when its estrogen component was small--matching in some of the lower blood concentrations measured during gestation, though still exceeding those that occur outside of pregnancy. Even cutting the rats' therapy to a single week, the equivalent of treating women for just 3 months, didn't reduce long-term protection.

Estrogen-only therapy worked less well, allowing 38 percent of the rats to develop cancer, and treatment with progesterone alone actually spurred the disease. Not only did all rats on the progesterone regimen get cancer, but each developed more tumors than did the carcinogen-exposed rats that were denied any treatment.

Though he is not yet sure how estrogen protects, Nandi told SCIENCE NEWS that "we think the predominant effect is going to be at the brain and pituitary-gland level." These organs may trigger the secretion of hormones that reduce the number of cellular receptors in breast tissue for hormones such as estrogen. The presence of fewer receptors for estrogen would reduce the breast's response to this hormone, which can fuel cancer growth.

Investigating hormonal simulation of pregnancy to reduce breast-cancer risk "is something that had to be done," says epidemiologist Malcolm C. Pike of the University of Southern California in Los Angeles. Nandi's new data suggesting that short-term therapy might work "is really very exciting," Pike maintains.

The USC researcher has data indicating that intensive treatments with novel contraceptives also block breast cancer (SN: 10/31/92, p. 298), and a start-up company is now making and testing them. Other researchers have developed drugs to selectively limit the effects of hormones in the breast. In the war on this cancer, Pike says, "I'm now very optimistic we're going to win."
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Author:Raloff, J.
Publication:Science News
Article Type:Brief Article
Date:Mar 6, 1999
Words:613
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