Genetic changes in breast tissue caused by pregnancy hormone helps prevent breast cancer

A full-term pregnancy at an early age is one of the most effective ways to reduce the lifetime risk of breast cancer, according to research pathologist Irma H. Russo, M.D., of Fox Chase Cancer Center in Philadelphia. A number of studies around the world have established that a full-term pregnancy by age 20 reduces breast cancer risk by half.

Previous studies by Russo and colleagues suggest that breast cells reach full maturity–a process called differentiation–only after a full-term pregnancy. Once this process is complete, the cells are less vulnerable to cancer-causing changes. An early pregnancy confers the strongest protection by limiting the time breast cells remain immature.

“A high-susceptibility or high-risk window exists early in life, between the start of ovarian function and the first pregnancy,” explained Russo. “During this period, the mammary gland has continuously varying characteristics influenced by ovarian and pituitary hormones. These traits change during pregnancy under the influence of embryonic and placental hormones.”

Russo’s laboratory has demonstrated that both pregnancy and a hormone produced during pregnancy, called human chorionic gonadotropin (hCG), inhibit breast cancer in rats. The placental hormone hCG promotes full maturation of breast cells and also wards off cancerous changes in these cells later.

“This led us to postulate that this hormone might be useful for breast cancer prevention in women,” Russo said. “Toward this goal, we designed experiments to learn, first, whether the protection conferred by hCG results from genetic changes specific to this hormone and, second, whether a similar genomic signature would result from either pregnancy or ovarian steroid hormones. Richard Wang, Ph.D., a postdoctoral associate in Russo’s laboratory, presented the results of the first study Sunday, April 17 at the 96th Annual Meeting of the American Association for Cancer Research. The study used virgin rats treated with a daily hCG injection compared to untreated virgin rats.

“Our results show that hCG induces permanent genetic changes in the mammary gland that are related to its breast cancer prevention effect,” said Wang.

In addition to Irma Russo, Wang’s Fox Chase co-authors include Jose Russo, M.D., director of Fox Chase’s Breast Cancer and the Environment Research Center; research associates Gabriela Balogh, Ph.D., and Fathima Sheriff, M.D.; research technicians Rachael L. Fernbaugh and Patricia A. Russo; and postdoctoral associates Daniel A. Mailo, Ph.D., and Raquel Moral, Ph.D.

The second study compared four groups of rats: a pregnant group, a virgin group treated with hCG, a virgin group treated with the hormones estrogen and progesterone (ovarian steroid hormones) and an untreated group. Daniel Mailo presented the results Tuesday, April 19 at the AACR meeting.

“These data show that both hCG and pregnancy induce permanent genetic changes that do not result from steroid hormones,” Mailo said. Mailo’s co-authors include Irma and Jose Russo, Sheriff, Balogh and research technician Rebecca Heulings.

A grant from the National Institutes of Health supported both studies.