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A new study of the breast cancer genes BRCA1 and BRCA2 shows that researchers still have a lot to learn about how these genes affect ethnic and racial minorities. The study shows that African-American families often have different mutations in these genes than white or Ashkenazi Jewish women -- but researchers don't yet know what these mutations mean for cancer risk.

BRCA1 and BRCA2 are genes that normally help prevent cancer. But when these genes have certain mutations (changes) in them, they can instead raise a woman's risk of developing breast and ovarian cancer. These mutations aren't very common in the general US population; only about 5% -10% of breast cancers are caused by them. But people in certain ethnic groups -- Ashkenazi Jews, for instance -- do seem to be more likely to carry dangerous mutations in BRCA1 and BRCA2.

The only way to find mutations in BRCA1 and BRCA2 is to have a genetic test. But most studies that have tested women for these genes have involved women with white European or Ashkenazi Jewish ancestry. Very little research has included African -Americans, Hispanics, or Asian -Americans. The new study tried to address this gap.

Researchers from the University of Chicago Medical Center recruited 155 families to participate. Half of the families (78) were white (non-Jewish, non-Hispanic), 43 were African-American, and 29 were Ashkenazi Jewish. Just 3 families were Hispanic and 2 Asian. All of them had already decided to be tested for BRCA1 and BRCA2 mutations because they had a strong family history of breast cancer, ovarian cancer, or both. The researchers analyzed the different BRCA mutations found in each ethnic group. They published their findings in this week's Journal of the American Medical Association.

Ashkenazi Jewish families had the highest rate of BRCA1 and BRCA2 mutations that are known to increase risk, followed by white families. African-American families had fewer of the BRCA mutations that are already known to be dangerous, and more of what the researchers called "variants of undetermined significance." Those are changes in the genes that researchers don't know enough about to say whether they're harmful, helpful, or have no impact at all.

"We don't know nearly enough and we need to study it more," said senior researcher Olufunmilayo Olopade, MD, professor of medicine and director of the Cancer Risk Clinic at the University of Chicago Hospitals. "We don't know whether these variants are important or not, or whether there are other genes we should be going after besides BRCA1 or BRCA2.

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Olopade and her team found hints that there may well be other genes involved in inherited breast cancer in some families. Of the 43 African-American families tested, 12 had no mutation at all in BRCA1 or BRCA2, and the researchers found no BRCA mutations in the Hispanic or Asian families. Yet all of these families had a strong history of the disease, suggesting genetic involvement.

One reason researchers know so little about breast cancer genes in minority families, Olopade said, is that very few minority women get genetic tests. There are simply too few minorities in the gene database for researchers to interpret the importance of the gene mutations they have.

"We need to get [minority women] tested and get them into clinical trials to find out what those variants mean," Olopade said.

One barrier to genetic testing is money. Olopade said the test costs about $3,000. Although private insurance and Medicare cover genetic testing for high-risk women, Medicaid does not. A handful of charitable groups also help pay for testing for low-income women at high risk. Olopade said the medical community needs to do more to make genetic testing available to minority women.

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Another barrier is knowledge. Olopade said doctors need to discuss genetic counseling and testing with minority women who have a family history of breast cancer, or early-onset breast cancer.

But not all women should be tested. The US Preventive Services Task Force recently issued its first-ever recommendation on the subject. It said that only women with specific family histories should be tested for BRCA1 and BRCA2 mutations (or sent for genetic counseling about testing). These women include:

• Women who have a relative known to have a dangerous mutation in one of these genes
• Women who have 2 first-degree relatives (mother, daughter, sister) with breast cancer, 1 of whom was diagnosed at age 50 or younger
• Women who have 3 or more first- or second-degree relatives with breast cancer diagnosed at any age
• Women who have a combination a breast and ovarian cancer in first- or second-degree relatives
• Women who have a first-degree relative who had breast cancer in both breasts
• Women who have 2 or more first- or second-degree relatives with ovarian cancer diagnosed at any age
• Women who have a first- or second-degree relative who had both breast and ovarian cancer at any age
• Women who have a male relative who had breast cancer
• Ashkenazi Jewish women with any first-degree relative who had breast or ovarian cancer
• Ashkenazi Jewish women who had 2 second-degree relatives on the same side of the family with breast or ovarian cancer

Women who do not have one of these family history patterns should not be routinely referred for genetic counseling and testing, the USPSTF said. The new recommendation appears in the Annals of Internal Medicine.

Citations: "Genetic Testing in an Ethnically Diverse Cohort of High-Risk Women: A Comparative Analysis of BRCA1 and BRCA2 Mutations in American Families of European and African Ancestry." Published in the Oct. 19, 2005 Journal of the American Medical Association (Vol. 294, No. 15: 1925-1933). First author: Rita Nanda, MD, of the Center for Clinical Cancer Genetics, University of Chicago Medical Center.

"Genetic Risk Assessment and BRCA Mutation Testing for Breast and Ovarian Cancer Susceptibility: Recommendation Statement." Published in the Sept. 6, 2005 Annals of Internal Medicine (Vol. 143, No. 5: 355-361). First author: US Preventive Services Task Force.