Statements based on evidence are accompanied by citation; statements without citation represent the consensus opinion of participating experts.

1. STATEMENT OF THE PROBLEM

The recent identification of genes associated with hereditary susceptibility to breast and ovarian cancer poses new challenges for health care professionals. Because of the increasing commercial availability of genetic testing, practitioners must determine the most appropriate process through which cancer susceptibility testing should be provided. In response to these issues, the American College of Medical Genetics, with support from the New York State Department of Health, has convened representatives of relevant professional societies, industry representatives, and consumer groups to develop these Guidelines to aid the health care professional with counseling and testing for genetic susceptibility to breast and/or ovarian cancer.

It is currently held that approximately 5 to 10% of breast cancer in the general population is associated with the inheritance of mutations that convey a very high risk of developing the disease (Claus et al 1996). Two genes - BRCA1 and BRCA2 - have been isolated and a number of tests have been developed to detect inherited mutations. Initial estimates of risk came from studies performed on families with large numbers of affected individuals. Based on such families, a BRCA1 or BRCA2 mutation was estimated to confer an up to 85% risk by age 70 of developing breast cancer, and (particularly for BRCA1) an up to 50% risk by age 70 of developing ovarian cancer, as well as significantly increased risks for colon, prostate, and perhaps other cancers (Easton et al 1993; Wooster et al 1995; Green 1997). In families with a smaller number of affected individuals, the risks may be different. Early studies support this notion, indicating a substantially reduced risk, for example, in mutation-positive Ashkenazi Jews without significant family history (Struewing et al 1997).

When a known mutation has been identified in a family, the finding of a "negative" result can provide a degree of reassurance for the individual being tested. The finding of a "positive" result can justify enhanced cancer surveillance. In both circumstances, however, the results can also have untoward consequences.

While many families have already benefitted from genetic susceptibility testing in research studies, testing in these studies has been provided in the context of extensive genetic counseling, education, and psychological support (e.g., Lerman et al 1996). Now that testing is available commercially, health care professionals will increasingly be asked about the availability of such testing by those who already have had cancer and by those who perceive themselves to be at risk. Unfortunately, at the present time, there continues to be a considerable degree of uncertainty regarding the sensitivity of different testing methodologies, the specific cancer risks associated with the various mutations, and the effectiveness of the interventions commonly recommended for those individuals found to have mutations. Legal issues concerning protection of confidentiality and potential abuse of genetic information by insurance companies or employers present additional challenges to both the provider and the consumer of these services (see Appendix XIV).

Therefore, before initiating the discussion of such testing, the clinician should determine whether the patient's history warrants it and must be committed to educating the patient as to the limitations and risks, as well as the benefits, of current testing. Patients who inquire about testing, but who are not at increased risk due to their personal and family history, also deserve consideration of their concerns, including an explanation of why testing may be inappropriate for them, a review of routine surveillance measures, and reassurance.