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Family History Ups Breast Cancer Risk Even Without BRCA Gene

Unknown mutations may account for increased odds, researchers say

MONDAY, Nov. 17 (HealthDay News) -- The risk of breast cancer for a woman with a strong family history is four times higher than that of the general population -- even if she does not carry one of the breast cancer-linked mutations of the BRCA gene, a new study finds.

And in women younger than age 40 without the BRCA mutations, but with a very strong family history, the risk is about 15 times higher than the general population, according to the Canadian researchers.

Over a six-year period, the researchers followed up nearly 1,500 women from 365 families who had tested negative for the so-called breast cancer gene mutations in BRCA1 and BRCA2.

The study shows that women with a strong family history but not the BRCA1 and BRCA2 mutations are still very much more at risk than the average woman, said study author Kelly Metcalfe, an associate professor of nursing at the University of Toronto.

The findings suggest there are other genetic mutations that play a role in breast cancer, Metcalfe said. She is to report the finding Monday at the American Association for Cancer Research's annual International Frontiers in Cancer Prevention Research meeting, in Washington, D.C.

About 184,000 new breast cancer cases and 40,000 breast cancer deaths are expected this year in the United States, according to the American Cancer Society.

To be included in the Canadian study, women had to have two or more relatives diagnosed with breast cancer before the age of 50 or three relatives with breast cancer at any age.

The researchers compared the rates of breast cancer among these women with a family history against rates found in the general population based on regional cancer registries.

Over the follow-up period, 15.2 of the women in the family history group would have been expected to get breast cancer, but 65 did -- a fourfold increased risk. Women with family histories who were under the age of 40 had a 15-fold higher risk, the researchers found.

To put these risks in perspective, Metcalfe said a typical woman who tests positive for BRCA1 or 2 has an 80 percent lifetime risk of getting breast cancer, while women such as those in her study with a strong family history but no BRCA1 or 2 mutation have about a 40 percent lifetime risk. The average woman has about a 10 percent lifetime risk of developing breast cancer, she said.

While other studies have found similarly increased risks of breast cancer among women with a strong family history, the current study adds to the information, Metcalfe said. "What we were able to observe were the differences in age," she said.

The new study confirms previous research, said Dr. Shawna Willey, director of the Betty Lou Ourisman Breast Health Center at the Lombardi Cancer Center at Georgetown University, in Washington, D.C.

Women with this strong family history might consider more frequent screening, including breast MRI, said Willey. "They could be a candidate for chemoprevention," she said, referring to the use of anti-cancer drugs such as tamoxifen in high-risk people.

More information

Find out more about BRCA at the U.S. National Cancer Institute.

SOURCE: Kelly Metcalfe, Ph.D., associate professor, nursing, University of Toronto; Shawna Willey, M.D., breast surgeon and director, Betty Lou Ourisman Breast Health Center, Lombardi Cancer Center, Georgetown University, Washington, D.C, and president, American Society of Breast Surgeons; Nov. 17, 2008, presentation, Frontiers in Cancer Prevention Research Conference, American Academy of Cancer Research, Washington, D.C.

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