Genetic Testing for Breast and Ovarian Cancer Susceptibility

Armen Hareyan's picture

One of the most heralded developments in the molecular genetics of cancer in recent years has been identification of the BRCA1 and BRCA2 genes responsible for familial breast/ovarian cancer syndrome. About 10 percent of women with these cancers carry inherited mutations in one of these genes. Carriers have a considerably elevated lifetime risk of developing breast or ovarian cancer, estimated at 50-70 percent and 10-30 percent respectively, and may also be at elevated risk for colon, prostate, fallopian tube, and peritoneal cancers.

Discovery of the BRCA genes has produced significant demand for genetic testing. Because both genes are large, and mutations are scattered throughout their entire sequence, scientists face considerable technical challenges in developing reliable, cost-effective tests. Clinicians as well face immense challenges in deciding who and when to test, whether or not to inform other family members of test results, how and where to record results, and how best to care for patients found to be mutation carriers.


Candidates for Screening. Since BRCA testing is costly, it generally is focused on individuals at high risk of being a mutation carrier. Occurrence of two or more cases of breast cancer prior to age 50 or ovarian cancer at any age is associated with a 10-20 percent probability of finding a mutation. Male breast cancer in the pedigree is particularly suggestive of BRCA2 mutation. The carrier frequency in the general population is about 1 in 500 (1 in 40 in the Ashkenazi Jewish population).

Genetic testing of a high-risk family is best focused on individuals who have already been affected by cancer. If a specific BRCA mutation is found, other family members can then be tested at less expense. Both false-positive and false-negative test results may occur due to detection of polymorphisms and failure to identify certain types of mutations, complicating the management of high-risk families in which a clearly deleterious mutation is not found.

Genetic testing is important in evaluating families with a strong history of breast and/or ovarian cancer, but should not be offered without pre- and post-test counseling. Genetic counselors play an important role in this process as they have special training and expertise in discussing the complex issues that surround this field. Issues for the physician and genetic counselor to discuss with anyone considering BRCA screening include: limitations of available tests; costs of the test and counseling; emotional impact of the results on herself and family members; insurance ramifications and potential for discrimination; and choices concerning clinical management if she is found to carry a BRCA mutation.

Issues of Discrimination. In April 1995, the U.S. Equal Employment Opportunity Commission issued guidelines clarifying that the 1990 Americans with Disabilities Act extends protection to individuals discriminated against on the basis of genetic information. More than 27 states have also extended some protection to genetic information. Nonetheless, patients justifiably have misgivings about the nonmedical consequences of a genetic finding. Misuse of genetic information can have devastating consequences