Findings Offer Complete View of Breast Cancer Gene Mutations in US Population

A study funded by the National Institutes of Health has provided the clearest picture yet of the prevalence in the U.S. population of mutations in two genes associated with an increased risk of breast cancer.

The genes are called Breast Cancer 1 ("BRCA1") and Breast Cancer 2 ("BRCA2"). In addition, the study identified key predictors for assessing which women are most likely to carry these genetic mutations.

To date, most of the studies on "BRCA1" and "BRCA2" mutations have focused on families known to be at high risk for breast cancer and on women who develop breast cancer at a relatively young age.

The study, published in an issue of journal "Cancer Research", looked at the prevalence and predictors of "BRCA1" and "BRCA2" mutations in under-studied groups of women, such as African Americans and older women.

"Studies of any notable size have focused almost exclusively on white women and young women," said one of the study's lead investigators, Elaine Ostrander, Ph.D., chief of the Cancer Genetics Branch in the National Human Genome Research Institute's Division of Intramural Research.

"This research clearly was needed to improve our means of assessing the likelihood of carrying "BRCA1" and "BRCA2" mutations in a wider spectrum of women."

The researchers examined the prevalence and predictors of "BRCA1" and "BRCA2" mutations in 1,628 women with breast cancer and 674 similar women without breast cancer, all of whom were participants in the National Institute of Child Health and Human Development's (NICHD's) Women's Contraceptive And Reproductive Experiences (CARE) study.

The women involved in the study were white and African American women, ages 35 to 64, who lived in the Atlanta, Detroit, Los Angeles, Philadelphia and Seattle metropolitan areas.

"The advantages of this study include its large sample size, inclusion of under-studied groups of women and the fact that the results are population based," said one of the study's co-authors, Robert Spirtas, Dr. P.H., former chief of NICHD's Contraception and Reproductive Health Branch and now retired.

Researchers found that 2.4 percent of the breast cancer patients had "BRCA1" mutations and 2.3 percent had "BRCA2" mutations.

"BRCA1" mutations were more common among white breast cancer patients, 2.9 percent, than among African American patients, 1.4 percent.

Breast cancer patients of Jewish ancestry were also significantly more likely to have "BRCA1" mutations than non-Jewish patients, 10.2 percent compared to 2.0 percent.

For "BRCA2", African American patients were slightly more likely to have mutations, 2.6 percent, than were white patients, 2.1 percent.

Based on their findings, the researchers went on to calculate the prevalence of "BRCA1" and "BRCA2" mutations in the general U.S. population.

Among white and African American women ages 35 to 64, the prevalence of "BRCA1" mutations is 0.06 percent and the prevalence of "BRCA2" mutations is 0.4 percent, the researchers estimated.

"These findings from our large, population-based study are compatible with earlier estimates made by extrapolating from smaller studies," said the study's other lead investigator, Kathleen Malone, Ph.D., Member of the Public Health Sciences Division at the Fred Hutchinson Cancer Center. 

"However, we found a slightly lower frequency of "BRCA1" mutations and higher frequency of "BRCA2" mutations."

"We think the difference lies in the fact that earlier studies were confined mainly to whites, and that African American women carry "BRCA2" mutations more often than white women."

The researchers also identified key predictors of whether a woman with breast cancer is likely to carry a "BRCA1" or "BRCA2" mutation.

Such information is important because it can help to improve means of assessing which women may benefit the most from genetic testing, increased breast cancer screening and other measures aimed at early detection, treatment or prevention.

The most significant predictors for "BRCA1" mutations were: Jewish ancestry, a family history of ovarian cancer and a family history of breast cancer occurring before age 45.

For "BRCA2" mutations, researchers uncovered fewer predictors and they had more modest effects.

Among the breast cancer patients studied, the only significant predictors of a "BRCA2" mutation were early age of onset (before age 45) in the patient herself or early onset of breast cancer in mother, sisters, grandmothers or aunts.

"These findings underscore why women need to learn as much as they can about their family health history and then share that information with their health-care professionals," said NIH Director Elias A. Zerhouni, M.D.

"However, it must be emphasized that the presence or absence of a predictive factor does not automatically equate with a high or low likelihood of carrying a breast cancer gene mutation."

"The majority of women with breast cancer - even those with a family history of the disease - do not carry mutations in these genes. These predictors need to be considered in the context of each woman's complete family health history."