Protective progeny: peptide treats and prevents breast cancer.

A synthetic version of a protein present in a woman's body during pregnancy is as effective against breast cancer as the current drug tamoxifen is, according to a study in rodents. The new substance may avoid tamoxifen's side effects.

Epidemiological research has estimated that, over her lifetime, the average woman has a 1-in-8 chance of developing breast cancer. However, among women who've had at least one full-term pregnancy, that risk is only 1 in 16, says James Bennett of the Albany (N.Y.) Medical College.

In earlier work, Bennett's team had determined that alpha-fetoprotein (AFP), a substance secreted by the liver of the fetus, is partially responsible for pregnancy's protective effect. Bennett and his colleagues at Albany Medical College set out to make a synthetic compound with AFP's effect.

The team synthesized a ring-shaped peptide that they called AFPep and tested it for both treatment and prevention of breast cancer. Team member Thomas Andersen presented the results on Nov. 1 in Baltimore at a meeting of the American Association for Cancer Research.

When the researchers daily gave AFPep, either orally or by injection, to mice with breast tumors, the peptide kept the cancer in check. The results with oral doses were especially encouraging because most peptides are quickly digested in the gut.

In separate, cancer-prevention experiments, the researchers exposed rats to cancer-causing chemicals and administered AFPep, tamoxifen, a combination of the two, or no treatment.

AFPep was as effective at preventing breast cancer in the rats as tamoxifen was. Physicians often prescribe tamoxifen to women who have already had a breast tumor and sometimes to other women at high risk of breast cancer. In the new experiments, either compound used alone reduced the number of rats that developed tumors by 23 percent compared with the number of untreated animals developing tumors.

The drug combination was even more effective. It yielded a 77 percent drop in cancer incidence compared with no treatment.

Because tamoxifen and AFPep inhibit cancer via different mechanisms, they can complement each other, says Bennett. Tamoxifen blocks binding of the hormone estrogen to cells. In roughly 70 percent of breast cancer cases, estrogen is responsible for cancer-cell proliferation.

AFPep, on the other hand, hinders the molecular step after estrogen binds to a cell. The peptide thwarts this process, called phosphorylation, thereby blocking estrogen-induced cell proliferation in a way not observed in other anticancer drugs.

Breast cancer typically becomes resistant to tamoxifen after 5 years of treatment. AFPep is effective against tumors that have grown resistant to tamoxifen, says Bennett. High doses of the peptide showed no toxicity in the mice or rats; tamoxifen, by contrast, causes uterine abnormalities in rodents.

"These are particularly interesting data," says Craig Jordan of the Fox Chase Cancer Center in Philadelphia. The new study "clearly means that we have the possibility of looking at different methods of attack for [estrogen]-dependent cancer," he adds.

Jordan notes that since AFPep appears to be potent when administered orally, it may be a cancer drug that people can take easily.