WASHINGTON -- Like humans, young rats that give birth have a reduced risk of breast cancer later in life. But a new study shows that this protective effect in animals is negated if they're exposed to an obesity-linked hormone during pregnancy.

The study, to be published online Nov. 1 in Cancer Prevention Research by Georgetown Lombardi Comprehensive Cancer Center scientists, suggests an important direction for research in women's health, particularly given obesity rates worldwide.

In humans, pregnancy initially increases breast cancer risk within the first five to seven years after birth, and then either permanently reduces the risk by nearly half in younger women, or increases the risk in women older than 30. The same pattern is seen in rats.

The link between obesity, pregnancy and breast cancer risk is only now being explored.

"We know that pregnant women who gain an excessive amount of weight have high blood levels of leptin -- a hormone made by fat tissue -- and that they have an increased risk of developing breast cancer after menopause," explains Leena Hilakivi-Clarke, PhD, a professor of oncology at Georgetown Lombardi, and lead author of the new study. "By studying these factors in animals, we hope to understand how they're linked."

For the study, the researchers looked at breast cancer risk after pregnant rats were exposed to leptin and what, if any, gene changes could be observed.

Their findings showed that similar to women, female rats had an initial increase in breast cancer risk after birth, but the risk eventually diminished to a level that was lower than in rats that did not give birth.

"This suggests pregnancy has a life-long protective effect against breast cancer in animals as it does in women," Hilakivi-Clarke explains.

But breast cancer risk in the rats exposed to leptin during pregnancy did not decrease. "This is concerning, as it suggests the exposure to the obesity-linked hormone negated the protective effect of birth on breast cancer risk."

To discover possible reasons for the differences in breast cancer risk, the researchers looked at gene patterns in the mammary glands of all the rats. "We saw a much different pattern among the rat groups," Hilakivi-Clarke says.

In women and animals, pregnancy permanently turns on genes that allow healthy breast cells to protect themselves against insults that can initiate cancer. These gene changes are believed to explain the dramatic drop in breast cancer risk in women who had a child before age 20.

"It appears that treating rats with leptin during pregnancy prevented the protective changes in genes from happening," Hilakivi-Clarke explains. "This work points to an important direction for research to prevent breast cancer in women since obesity is an epidemic," Hilakivi-Clarke concludes.

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This study was supported grants from the National Cancer Institute (1P30-CA51008; R01 89950; 1R01CA164384; U54 CA000970 and U54 CA149147).

In addition to Hilakivi-Clarke, authors include Sonia de Assis, Mingyue Wang, Lu Jin and Kerrie B. Bouker, all of Georgetown Lombardi. The authors report having no personal financial interests related to the study.

About Georgetown Lombardi Comprehensive Cancer Center

Georgetown Lombardi Comprehensive Cancer Center, part of Georgetown University Medical Center and MedStar Georgetown University Hospital, seeks to improve the diagnosis, treatment, and prevention of cancer through innovative basic and clinical research, patient care, community education and outreach, and the training of cancer specialists of the future. Georgetown Lombardi is one of only 40 comprehensive cancer centers in the nation, as designated by the National Cancer Institute, and the only one in the Washington, DC, area. For more information, go to http://lombardi. georgetown. edu .

About Georgetown University Medical Center

Georgetown University Medical Center is an internationally recognized academic medical center with a three-part mission of research, teaching and patient care (through MedStar Health). GUMC's mission is carried out with a strong emphasis on public service and a dedication to the Catholic, Jesuit principle of cura personalis -- or "care of the whole person." The Medical Center includes the School of Medicine and the School of Nursing & Health Studies, both nationally ranked; Georgetown Lombardi Comprehensive Cancer Center, designated as a comprehensive cancer center by the National Cancer Institute; and the Biomedical Graduate Research Organization (BGRO), which accounts for the majority of externally funded research at GUMC including a Clinical and Translational Science Award from the National Institutes of Health.