Portal de Periódicos da CAPES

HCG Shows Promise for Preventing Breast Cancer

2005; Wolters Kluwer; Volume: 27; Issue: 11 Linguagem: Inglês

10.1097/01.cot.0000302791.17952.0a

1548-4688

Charlene Laino,

Nutrition, Genetics, and Disease

ANAHEIM, CA—A hormone naturally produced during pregnancy shows promise for preventing breast cancer, according to data presented here at the American Association for Cancer Research Annual Meeting. In animal studies, the hormone human chorionic gonadotropin (HCG) activated tumor-suppressor genes, suppressed cell division, and induced other genetic changes indicative of an anti-breast cancer effect, said Irma H. Russo, MD, Chief of Molecular Endocrinology at Fox Chase Cancer Center.Figure: Irma H. Russo, MD: Our goal is to eventually use this as a breast cancer preventive in women, just like tamoxifen. But unlike tamoxifen, HCG is normally produced by the body and has no toxic effects.“Our goal is to eventually use this as a breast cancer preventive in women, just like tamoxifen. But unlike tamoxifen, which has been linked to an elevated risk of endometrial cancer, HCG is normally produced by the body and has no toxic effects,” she explained. Early Pregnancy Cuts Breast Cancer Risk The HCG story really started back in the 1700s when physicians observed that breast cancer was more common in nuns than in other women, Dr. Russo said. “Over the years, the link between having children and breast cancer protection, particularly if you have children when you're young, became very solid.” With a number of studies around the world eventually showing that a full-term pregnancy by age 20 years cuts the risk of breast cancer in half, her lab sought to find out why. “What we found is that rats that were given carcinogens when they're young, virginal, and in puberty develop breast tumors,” she said. “But if you give the same drug after pregnancy, the animals do not develop tumors.” Now that the researchers knew that there is a risk window early in puberty, when the ovaries start working and the mammary gland is developing, “we wanted to try to manipulate it and eliminate it,” Dr. Russo said. “We knew pregnancy does it, but the question is, can we do it with hormones?” The researchers tested oral contraceptives, but they didn't do the trick. So they turned to HCG, a hormone made by placental cells that attach the fetus to the uterine wall. It's what early pregnancy tests detect in the urine and is an ingredient in the hormone cocktail given to induce ovulation in women undergoing in vitro fertilization. Prevents Breast Cancer in Rats HCG seemed to do the job, according to the new studies that Dr. Russo and colleagues presented at the AACR meeting. In one set of experiments, they gave rats that had just reached puberty a carcinogen to induce breast tumors and then gave the rats two weeks of HCG supplements. By comparing biopsy samples taken before and after the animals took HCG, they found that the hormone reduced cell division, induced expression of tumor suppressor genes, and decreased the number of cells that expressed estrogen receptors—all signs that HCG was working just like an anti-cancer drug, Dr. Russo said. The team then looked at the set of genes activated in the mammary gland of the virgin rat during pregnancy and compared that with the changes in the genetic signature in the mammary gland after treatment with HCG. For that study, the researchers compared an untreated group of virgin rats with three other groups of rats: a pregnancy group in which the rats were mated; a virgin group treated with a daily intraperitoneal injection of 100 IU of HCG for 21 days; and a virgin group treated with estradiol and progesterone. The researchers extracted RNA from the mammary gland tissues of the four groups of animals at 42 days post-treatment (or postpartum in the case of the pregnant rats), times when the mammary glands exhibit their lowest susceptibility to carcinogenesis. Then, standard microarray techniques were used to study the gene expression profiles. Compared with the untreated virgins, there was a “complete change in the genetic signature of both the pregnant rats and the rats treated with HCG,” Dr. Russo said. “An early pregnancy modifies the genetic signature for life. And giving HCG modifies the genetic signature for life.” There was no change in the rats given estrogen and progesterone. Other Researchers Optimistic In humans, Dr. Russo foresees a day in the near future when women at high risk of breast cancer could take HCG for a short time during puberty, thereby modifying their genetic signature in such a way as to confer protection for life. Measuring levels of HCG in the blood could also help doctors to determine who is at risk for breast cancer and whether a woman is responding to treatment. Timothy Richard Rebbeck, PhD, a molecular epidemiologist at the University of Pennsylvania, said the studies “reflect the work of Russo's lab, which is brilliant.” “The notion of taking a very well-established risk factor like pregnancy that's not really modifiable and taking it to the next step and mimic it to prevent breast cancer is very innovative.” That said, he added, further studies are needed to tease out other factors that may be working in concert with HCG to exert an anti-tumor effect.