Study: Does expanded genetic testing benefit Jewish women diagnosed with breast cancer?

IN-DEPTH REVIEW OF RESEARCH

Study background:

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.

Researchers of this study wanted to know:

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?

Population(s) looked at in the study:

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.

Study findings:

Of the 1,007 patients in the study:

• 104 women (10.3%) had a BRCA1 or BRCA2 founder mutation.
  • These women were more likely to be younger at age of diagnosis and more likely to have a family history of breast or ovarian cancer than were patients with no founder mutation.
• 903 (90%) had none of the three Jewish founder mutations in BRCA1 or BRCA2.
  • Of these 903 women, 865 women tested negative for any known mutation associated with breast cancer
• A total of 142 women in the NYBCS tested positive for any mutation. Of these women:
  • 104 (74%) had a BRCA founder mutation
  • 7 (5%) had a non-founder BRCA mutation
  • 31 (22%) had a mutation in another gene
    • 29 of these mutations were in the CHEK2 gene
      • Of the 29 CHEK2 mutations, 24 were a known Ashkenazi Jewish founder CHEK2 mutation, c.1283C>T. The other five CHEK2 mutations are common in people of European descent.
    • 1 mutation each was found in BRIP1 and NBN
  • Approximately half of women with an inherited mutation in a breast cancer gene had no family history of breast or ovarian cancer.

Limitations: 

• This study looked only at Ashkenazi Jewish women with invasive breast cancer. Women who were not Ashkenazi Jewish, had non-invasive breast cancer or ovarian cancer, or were cancer-free were not studied.
• Researchers tested only some known breast cancer genes for mutations. Mutations in other cancer genes, such as genes for Lynch syndrome, were not examined.
• The panel test used in this study examined 23 different genes. Although scientists know a lot about many of them, they are still studying these and other genes, meaning cancer risk information is limited and expected to change with further research.
• There are likely mutations that increase risk of breast cancer in other, unknown genes

Conclusions:

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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Posted 9/13/17