American women who do not have a strong family history of breast cancer should not feel the need to be tested for BRCA1, the gene whose mutations are associated with a predisposition to breast cancer.
Cancer researchers, led by Dr. Beth Newman* of the Lineberger Comprehensive Cancer Center at the University of North Carolina at Chapel Hill and Dr. Mary-Claire King* of the University of Washington in Seattle, draw this conclusion after a case-control study of women of all ages with breast cancer, selected without regard to their family history.
Their study is published in the March 25 issue of JAMA, the Journal of the American Medical Association.
“Most of the inherited breast cancer attributable to BRCA1 has been studied in high-risk families with many cases of breast cancer,” said King, who mapped the gene in 1990. “There has been no previous analysis of BRCA1 status in a series of patients identified simply because they have breast cancer, regardless of their ancestry and at any age.”
The researchers (Newman is a former graduate student of King) studied 211 women from North Carolina with breast cancer. White and black patients were included in approximately equal numbers, as part of Newman’s ongoing epidemiological study of the genetic and environmental causes of breast cancer, which now includes more than 1,800 women in North Carolina.
The patients were women aged 20 to 74, diagnosed as having a first invasive breast cancer between 1993 and 1996. They were asked to participate regardless of their age when diagnosed, or the incidence of breast cancer in their families.
“The question was, just how common are these mutations in the American population? In breast cancer patients, both white and black?” said King. “It’s a complicated question, because one must fully test the entire BRCA1 gene, not just a few of the known mutations.”
The researchers screened the complete gene sequence of BRCA1 in each patient, using new screening methods developed by Dr. Hua Mu,* a genetic epidemiologist in the King lab.
The genetic analysis showed that only three of the 120 white women with breast cancer had disease-related BRCA1 mutations (3.3 percent), and none of the 88 black women had disease-related mutations in BRCA1 (0 percent). (There were also three Native American women, none of whom had such mutations.)
“From this study we can conclude that for the general American population, widespread screening is not necessary,” said King. “In contrast, for populations with relatively common ancient gene mutations, such as the Jewish community in America, genetic evaluation of BRCA1 and BRCA2 (the second gene found with disease-causing mutations) can be worthwhile.”
“BRCA1 mutations are sufficiently frequent in families with both breast and ovarian cancer, or with at least four cases of breast cancer (at any age), that genotyping might be considered,” the researchers conclude.
“The emerging picture of BRCA1 population genetics involves complex interactions of family history, age and genetic history, all of which should be taken into account when considering genetic testing or interpreting results.”
A similar evaluation of inherited BRCA2 mutations in the same patients is in progress.
The study was supported in part by the National Institutes of Health Specialized Program of Research in Excellence in Breast Cancer.
* King and Newman hold Ph.D.s; Mu has an M.D. and a Ph.D.