Researchers Pinpoint Genes' Role in Breast Cancer

Mutations to BRCA1 or BRCA 2 genes increase risk

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HealthDay Reporter

THURSDAY, Oct. 23, 2003 (HealthDayNews) -- Women who carry the BRCA1 or BRCA2 gene mutation have an 82 percent risk of developing breast cancer by the time they are 80 years old.

The silver lining is that even those with the highest genetic risk can stave off the disease with exercise and maintaining a healthy weight when they're younger, says a study in the Oct. 24 issue of Science.

"[The study authors] have characterized probably as best as can be done to date the incidence and risk of developing breast cancer if you fit into this particular group of women," says Dr. Len Lichtenfeld, deputy chief medical officer of the American Cancer Society. "These can be used as guidelines now. They are probably the best and most accurate guidelines that we have to date."

Past risk estimates for women with one of the mutations ranged from 25 percent to 80 percent, but generally focused on women who had a strong family history of breast cancer.

"We wanted to see what was the likelihood of carrying the mutation regardless of family history," says Jessica Mandell, the primary genetic counselor for the study. Mandell, who is with the Human Genetics Graduate Program at Sarah Lawrence College in Bronxville, N.Y., was also the study's research coordinator and a co-author.

Mandell and her colleagues looked at 1,008 Ashkenazi Jewish women with invasive breast cancer who were part of the New York Breast Cancer Study Group. This is an ethnically homogenous group and the mutations, if present, could be expected to be found in specific areas of the BRCA1 and BRCA2 genes.

"In the general population, you would have to look at the entire gene sequence, which is a much more complicated process," Lichtenfeld explains. "By selecting Ashkenazi Jews, they were able to hone in on a couple of places on the gene where you would expect to find an abnormality."

The researchers also found the lifetime risk of ovarian cancer for women with the BRCA1 mutation was 54 percent and, for women with the BRCA2 mutation, 23 percent.

They also found that women born before 1940 had a lower risk of breast cancer than women with the mutation who were born after 1940, strongly suggesting that environmental factors are also at play here. Women who had had a healthy weight and who exercised when they were adolescents had a lower risk.

Overall, about 10 percent of the group (104 women) carried the BRCA1 or BRCA2 mutation.

The risk in this group of developing breast cancer by the age of 40 was 20 percent; by the age of 60, 55 percent; and by the age of 80, 82 percent, the researchers found.

There were other startling differences in breast cancer risk. Women carrying one of the mutations who were born before 1940 had a 24 percent risk of developing breast cancer by age 50. Among those born later, however, that risk jumped to 67 percent.

"This has broad implications because it means that there are other factors that are occurring in the general population that are accounting for increased incidence of breast cancer," Lichtenfeld says.

Based on their findings, the researchers speculate that all women could help reduce their risk of breast cancer by being physically active and maintaining a healthy weight during adolescence.

Significantly, half of the women with a mutation did not have a history of breast cancer in their immediate family.

"We certainly expected to find some women who didn't have a family history but we didn't necessarily predict it would be an equal 50/50 split," Mandell says. "There are a lot of things that can mask the genetic mutation being passed on, for example, inheritance through men in the family, small family size or few women in the family."

What this means is that genetic screening may be appropriate for more women than originally thought. Certainly, if you have a family history of breast cancer you might consider being tested. In addition, age, ancestry and factors such as weight, exercise patterns, tobacco use, age at first menstruation and exposure to hormones need to be taken into account, the researchers say.

The results of a second study, this one appearing in the Oct. 23 issue of Breast Cancer Research, may provide another reason for testing for certain women. This study found that women with the BRCA1 mutation have a poor long-term survival when they develop breast cancer. Chemotherapy, however, can mitigate this effect.

Any decisions having to do with genetic testing and treatment need to be discussed with your physician.

More information

For more on breast cancer genes, visit the Berkeley Lab. The National Cancer Institute has information on genetic screening.

SOURCES: Len Lichtenfeld, M.D., deputy chief medical officer, American Cancer Society, Atlanta; Jessica Mandell, M.S., C.G.S., Human Genetics Graduate Program, Sarah Lawrence College, Bronxville, N.Y.; Oct. 24, 2003, Science

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