Results of a study funded by the National Institutes of Health (NIH; Bethesda, Maryland) have "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, i.e., Breast Cancer 1 (BRCA 1) and Breast Cancer 2 (BRCA 2), the NIH said.
However, to date, most of the studies on those two gene 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. Researchers estimated that inherited mutations play a role in anywhere from 5% to 27% of all breast cancer cases, although the majority of breast cancer cases are caused by genetic changes that occur during a woman's lifetime.
The new study, published last week in the journal Cancer Research, looked at the prevalence and predictors of BRCA 1 and BRCA 2 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, PhD, 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 BRCA 1 and BRCA 2 mutations in a wider spectrum of women."
Ostrander was previously head of the genetics program at the Fred Hutchinson Cancer Research Center (Seattle), which is the institution that led the study, the NIH said.
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 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 the 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, PhD, former chief of NICHD's Contraception and Reproductive Health Branch and now retired, the NIH said.
Researchers found that 2.4% of the breast cancer patients had BRCA1 mutations and 2.3% had BRCA2 mutations. BRCA1 mutations were more common among white breast cancer patients (2.9%) than among African-American patients( 1.4%).
Breast cancer patients of Jewish ancestry also were "significantly more likely" to have BRCA 1 mutations than non-Jewish patients (10.2% compared to 2.0%). For BRCA2, African-American patients were slightly more likely to have mutations, or 2.6%, than were white patients, or 2.1%.
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% and the prevalence of BRCA2 mutations is 0.4%, the researchers estimated, according to the NIH.
"These findings from our large, population-based study are compatible with earlier estimates made by extrapolating from smaller studies. However, we found a slightly lower frequency of BRCA1 mutations and higher frequency of BRCA2 mutations," said the study's other lead investigator, Kathleen Malone, PhD, member of the Public Health Sciences Division at the Fred Hutchinson Cancer Center. "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. According to the NIH, such information is important because it can help to improve means of assessing which women may benefit the most from genetic screening, 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, or 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 healthcare professionals," said NIH Director Elias Zerhouni, MD. "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."