Genetic Testing for Breast and Ovarian Cancer Susceptibility

 

BACKGROUND:

BRCA1 and BRCA2 are believed to play a role in 5-10% of breast cancer cases and in most families with an inherited predisposition to breast and ovarian cancer. Inherited mutations in the BRCA1 gene on chromosome 17q and in the BRCA2 gene on chromosome 13q are associated with increased susceptibilities to breast and ovarian cancer. These genes, and hence the resulting susceptibilities, are inherited in an autosomal dominant pattern. In families with a strong family history of breast and/or ovarian cancer, the estimated cumulative risk of developing breast cancer by age 70 in carriers of the mutated BRCA1 gene is 85% and the estimated risk for ovarian cancer by age 70 is 63%. In families with a strong family history of breast cancer, women with BRCA2 mutations appear to have similar breast cancer risks as BRCA1 mutation carriers, and a moderately increased risk of ovarian cancer. In contrast to BRCA1 mutations, inherited BRCA2 mutations are associated with an increased risk of breast cancer in men. Sequencing of these genes has identified a wide variety of mutations which makes screening for mutations technically difficult. An exception is testing in the Ashkenazi Jewish population. Recurrent mutations of BRCA1 and BRCA2 may together account for one quarter of all early onset breast cancer in Jewish women. In addition, one in fifty individuals of Ashkenazi Jewish descent is estimated to carry a mutation in one of these genes. The high frequency of these specific recurrent mutations makes mutation detection technically feasible in this population. Testing for mutations in BRCA1 and BRCA2 in individuals outside of the Ashkenazi Jewish population and in Ashkenazi Jewish individuals negative for the common mutations requires full gene sequencing, a very costly and labor intensive technique.

Genetic testing in the Ashkenazi Jewish population allows an individual with breast or ovarian cancer to potentially learn if BRCA1 or BRCA2 is responsible for her cancer. In doing so, she may learn more about her risk of developing a second cancer, as well as the chances of her children and other relatives developing cancer. In addition, healthy individuals who have a family history of breast or ovarian cancer but who have not developed cancer themselves may be able to learn more about their chance of developing these cancers. This information is a valuable resource in developing management plans for the early detection of cancers and when considering prophylactic surgery.

INDICATIONS FOR TESTING:

  • Ashkenazi Jewish women with premenopausal breast cancer.

  • Ashkenazi Jewish women with ovarian cancer.

  • Ashkenazi Jewish men with breast cancer.

  • Ashkenazi Jewish women and men with a family history of early onset breast cancer, male breast cancer, and/or ovarian cancer.

  • Ashkenazi Jewish women and men who are relatives of known BRCA1 or BRCA2 mutation carriers.

SAMPLE REQUIREMENTS:

Blood: Two 5 ml purple top (EDTA) vacutainers of whole blood inverted several times to mix. Forward within 48 hours at room temp.

** A pedigree documenting family history must accompany the sample. Samples will only be accepted from health care professionals adhering to current professional guidelines regarding BRCA1/2 testing.

INTERPRETATION:

PCR based assays are used to detect the common, recurrent mutations seen in the Ashkenazi Jewish population (BRCA1 185delAG, BRCA1 188del11, BRCA1 5382insC, BRCA2 6174delT).

Report will include test results and background information.

COUNSELING ISSUES:

  1. Due to the complex medical and psychosocial issues related to genetic cancer susceptibility testing, samples will be accepted from health care professionals adhering to current professional guidelines regarding BRCA1/2 testing (available upon request).

 

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