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June 2008

Updated Test Improves Detection for Breast and Ovarian Cancer Gene

Mary Beattie, M.D.
UCSF Cancer Risk Program

Patients who tested negative for a BRCA1 and BRCA2 genetic mutation may still be at risk for familial breast or ovarian cancer. Recent research found that standard genetic testing failed to detect cancer-associated mutations in the BRCA1 and BRCA2 genes in about 12 percent of patients at very high risk of hereditary breast and ovarian cancer.

As genetic testing technology has improved, detection rates for BRCA1 and BRCA2 mutations in high-risk populations has increased. In 2002, a "rearrangement panel" in the BRCA1 and BRCA2 genes became available and became part of standard BRCA testing. In 2006, research of families at very high risk of hereditary breast and ovarian cancer detected additional rearrangements in BRCA1 and BRCA2. In response to these findings, a new test to detect these rearrangements in the BRCA1 and BRCA2 genes was developed.

This new technology, called BRACAnalysis® Rearrangement Test (BART), detects rare, large cancer-associated rearrangements of the DNA in the BRCA1 and BRCA2 genes, which were previously undetected by standard genetic testing called comprehensive BRACAnalysis®. BART and BRACAnalysis® were developed by Myriad Genetics Inc., the single supplier of BRCA1 and BRCA2 testing in the United States.

BART, which is a simple blood test, is recommended for patients who have a strong family history of breast or ovarian cancer. It is estimated that about 1 percent of individuals who meet the family history criteria for BART will have a mutation detected by the test. The test is available at leading medical centers where genetic testing and screening are offered, such as the UCSF Cancer Risk Program. BART is not part of standard BRCA testing and must be special ordered.

BRCA1 and BRCA2 Genetic Mutations

Discovered in the 1980s, BRCA1 is a gene on chromosome 17 that is involved in tumor suppression. Female carriers of germline BRCA1 mutations have a lifetime risk of breast cancer exceeding 80 percent and of ovarian cancer approaching 60 percent. BRCA2, another susceptibility gene for breast and ovarian cancer, is found on chromosome 13. Carriers of BRCA2 mutations have a similar risk of breast cancer and a more moderately increased risk of ovarian cancer compared to those with BRCA1 mutations. BRCA1 and BRCA2 mutations are also associated with an increase in prostate and colon cancers in men.

A recent studyof 3,181 breast cancer patients in Northern California— the largest study to date to track the prevalence of BRCA1 mutations among breast cancer patients in four ethnic and racial groups — found that the mutation crosses all ethnic and racial boundaries, providing crucial information that could help doctors decide which patients to refer to genetic counseling and testing.Researchers also hope that it prompts doctors to develop patient education materials on breast cancer and genetic testing that is culturally sensitive and language specific.

The BRCA1 genetic mutation is known to be highest among Ashkenazi Jews. However, the studyfound that although Ashkenazi Jewish women with breast cancer had the highest rate of the BRCA1 mutation at 8.3 percent, Hispanic women with breast cancer were next most likely, with a rate of 3.5 percent. Non-Hispanic whites with breast cancerhad a 2.2 percent rate, followed by 1.3 percent of African-American women of all ages.Among young African-American breast cancer patients under age 35, the mutationwas the highest at16.7 percent. It was the lowest amongAsian-American women at 0.5 percent.

When Is BART Recommended?

If your patient meets the following criteria, she may benefit from BART testing:

  • Family with an inherited pattern of cancer but no previously identified mutation
  • Family history of cancer meets the BART testing criteria (see below)
  • Initial testing produced a result of either "no mutation detected" or "genetic variant of uncertain significance" or "genetic variant, favor polymorphism"
  • Meets criteria above and tested negative for a BRCA mutation prior to August 2006

BART Testing Criteria

Patients who already tested negative for a deleterious mutation by BRACAnalysis®, may meet criteria for additional testing if they meet the following criteria regarding their condition and family history:

  • Condition — Breast cancer before age 50
    Family History — Two or more relatives with breast cancer before age 50 or ovarian cancer at any age *

  • Condition — Ovarian cancer at any age
    Family History — Two or more relatives with breast cancer before age 50 or ovarian cancer at any age *

  • Condition — Male breast cancer at any age
    Family History — Two or more relatives with breast cancer before age 50 or ovarian cancer at any age *

  • Condition — Breast cancer at or after age 50 and ovarian cancer at any age
    Family History — One or more relatives with breast cancer before age 50 or ovarian cancer at any age *

  • Condition — Breast cancer before age 50 and ovarian cancer at any age
    Family History — No additional relatives required

  • Family History — Patients with a known large rearrangement in their family

* At least one relative must be a first- or second-degree relative.

Cancer Risk Program

The UCSF Cancer Risk Program, established in 1996, is a comprehensive genetic counseling service for families with a history of cancer. Genetic counselors assess personal and family history, provide education and counseling and, when appropriate, offer genetic testing for cancer predisposition genes.

Services include:

  • In-depth cancer risk assessment based on personal and family history
  • Education about the genetics of cancer for patients and their families
  • Genetic testing, when appropriate and desired
  • Personalized cancer screening and prevention plan, including lifestyle changes, in collaboration with the patients referring physician
  • Psychological support
  • Access to clinical trials for cancer detection and prevention
  • Classes about inherited cancer predisposition; risks of developing breast, ovarian, colorectal and other cancers; and prevention and early detection procedures

For more information, contact the Physician Referral Service at UCSF Medical Center:

Phone (888) 689-UCSF or (888) 689-8273

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