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


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Jewish women with breast cancer who previously tested negative for the three most common BRCA mutations

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Checked Breast cancer survivors

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Checked Women over 45

Checked Special populations: Jewish women diagnosed with breast cancer


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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)

Contents

At a glance Clinical trials
Findings                      In-depth                                        
Guidelines Limitations 
Questions for your doctor                     Resources and references                             


STUDY AT A GLANCE

This study is about:

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. 

Why is this study important?

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? 

Study findings: 

  • This study tested 1,007 Ashkenazi Jewish women with breast cancer for mutations in 23 different breast cancer genes.
    • 903 of these women did not carry any of the three BRCA founder mutations. 
      • 7 women (0.8%) carried a unique mutation in BRCA1 or BRCA2.
      • 31 women (3.4%) carried a harmful mutation in another breast cancer gene.

What does this mean for me?

  • If you are an Ashkenazi Jewish women diagnosed with breast cancer:
    • Genetic testing may affect your treatment decisions.
    • If you have never had genetic testing, speak with your health care provider about genetic counseling and testing for a BRCA or other inherited mutation which can cause breast cancer.
    • If you had genetic testing only for the three BRCA founder mutations commonly found in Jewish people and you tested negative, you may benefit from expanded genetic testing. 
    • Expanded genetic testing is often covered by insurance and low-cost options are available for those without insurance coverage. 
    • Even if you have no additional family history of cancer, you may benefit from genetic testing. 
  • If you have been diagnosed with breast cancer and you are not of Ashkenazi Jewish descent, you may benefit from genetic counseling and testing. Although BRCA mutations are especially common in Jewish people, mutations have been found in people of every race and ethnicity. 

Expert Guidelines

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:

  • diagnosed with breast cancer at any age or stage. 
  • diagnosed with high-grade prostate cancer at any age. 

Any person diagnosed with any of the following cancers meets NCCN Guidelines regardless of their ethnicity:

  • Ovarian, fallopian tube or primary peritoneal cancer diagnosed at any age or stage. 
  • Pancreatic cancer diagnosed at any age or stage. 
  • Metastatic prostate cancer.
  • Breast cancer diagnosed at, or younger than age 50.
  • Triple-negative breast cancer diagnosed at, or younger than age 60. 
  • Male breast cancer.
  • More than one breast cancer diagnosis in the same person.
  • Breast cancer at any age and a family history of breast, ovarian, pancreatic or high-grade prostate cancer. 

These guidelines are up-to-date as of 10/04/19

Questions To Ask Your Health Care Provider

  • I previously tested negative for the BRCA founder mutations. Should I be tested for other BRCA mutations?
  • Should I have panel testing for mutations in other, non-BRCA breast cancer genes?
  • If I test positive for a mutation in other breast cancer genes, what does that mean for me and my family as far as screening, cancer prevention, and treatment choices?
  • My insurance will not pay for genetic testing. Are there other options for me to get testing? 

Open Clinical Trials

  • 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.

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

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