Breast cancer survivors
Women under 45
Women over 45
Special populations: Jewish women diagnosed with breast cancer
BRCA1 and BRCA2 mutations are common in people of Eastern European (Ashkenazi) Jewish descent. About 2% of all Ashkenazi Jewish people will test positive for one of three common mutations in these genes. Genetic testing for Jewish people sometimes focuses on only the three most common mutations. For Jewish women with breast cancer, little is known about their chance of carrying a different hereditary mutation that may increase risk. This study looked at expanded genetic testing in Jewish women diagnosed with breast cancer to learn how often they carried mutations other than the three most common BRCA gene mutations found in Ashkenazi Jewish people. (09/13/17)
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The benefit of doing additional genetic testing for Jewish breast cancer survivors who tested negative for the three common Jewish BRCA mutations. Researchers wanted to examine if additional genetic testing would find other inherited mutations within BRCA1, BRCA2, or in other genes that also increase risk of breast cancer.
A founder mutation is a mutation that is common in people who come from a distinct population. In the Ashkenazi Jewish population, three founder mutations, two in BRCA1 and one in BRCA2 have been identified. Ashkenazi Jewish women who carry one of these mutations are at much greater risk of being diagnosed with breast and/or ovarian cancer than Ashkenazi women who do not carry a founder mutation. Having this information can help guide women in their breast cancer treatment choices. But what about Ashkenazi Jewish women diagnosed with breast cancer who test negative for the BRCA founder mutations? What is the chance they may have inherited a unique BRCA mutation or a mutation in another breast cancer gene? How does knowing this additional genetic information affect their medical decisions and health outcomes?
The National Comprehensive Cancer Network (NCCN) is a consortium of cancer and genetics experts that publishes consensus guidelines for genetic testing for inherited mutations that increase cancer risk. NCCN guidelines recommend referral for genetic counseling and testing for people diagnosed with the following cancers:
Any person of Ashkenazi Jewish ethnicity with the following, meets NCCN Guidelines for genetic counseling and testing:
Any person diagnosed with any of the following cancers meets NCCN Guidelines regardless of their ethnicity:
These guidelines are up-to-date as of 10/04/19
NCT03351803: BRCA Founder Outreach Study (BFOR). The study offers BRCA genetic testing for the three common founder mutations to women and men of Ashkenazi (Eastern European) Jewish ancestry, age 25 or older. The study is open to people who live in the Boston, New York, Los Angeles or Philadelphia metropolitan areas.
Both men and women who carry a BRCA mutation have a significantly increased lifetime risk of several types of cancer. People of any race or ethnicity can test positive for a BRCA1 or BRCA2 mutation. Between 1 in 400 and 1 in 800 people in the general U.S. population has an inherited BRCA mutation. That number increases to about 1 in 40 among people of Eastern European Jewish descent. However, many Ashkenazi Jewish women who have been diagnosed with breast cancer test negative for the three founder mutations. In the past, when the cost of genetic testing was much higher, Jewish people with breast cancer sometimes might only undergo limited genetic testing looking only for the three most common founder mutations. Drs. Tom Walsh, Mary-Claire King, and colleagues published a retrospective study in JAMA-Oncology looking at mutations in known and suspected breast cancer genes among the New York Breast Cancer Study Participants. They wanted to know if these women would benefit from genetic sequencing of all breast cancer genes, including BRCA1 and BRCA2, in addition to targeted testing for the Jewish BRCA founder mutations.
How common are unique mutations in BRCA1 and BRCA2 and how common are mutations in other breast cancer genes in Ashkenazi Jewish women diagnosed with breast cancer?
Researchers looked at DNA and data collected from 1996-2000 from 1,007 participants in the New York Breast Cancer Study (NYBCS). All participants were Ashkenazi Jewish women diagnosed with invasive breast cancer, and were not selected based on family history or age at diagnosis. Their DNA had previously been studied for the three common Jewish BRCA mutations. In this new study, researchers used a panel test to identify unique mutations in BRCA1, BRCA2, and other genes known to increase breast cancer risk. They looked at results based on BRCA status, family history, and age at diagnosis.
Of the 1,007 patients in the study:
The results of this study suggest that Ashkenazi Jewish women who have been diagnosed with breast cancer and have tested negative for the three BRCA founder mutations should talk to their health care provider to see if they should consider genetic testing for other mutations in BRCA1, BRCA2 as well as other breast cancer genes. Share this study with your health care provider to see if additional genetic testing makes sense for you.
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