BRCA1/2 testing: Complex themes in result interpretation

Since the cloning of BRCA1 and BRCA2, genetic testing for breast and ovaria n carrier susceptibility has became more widespread. However, interpretatio n of test results is not always straightforward. To illustrate this point, five vignettes adapted from actual cases are presented. As these cases demo nstrate, in many high-risk families, a deleterious mutation in BRCA1 or BRC A2 is not identified in an affected proband, There are several potential ex planations for such a finding, namely that an undetected mutation in BRCA1 or BRCA2 may exist, or there could be a mutation in a rare or undiscovered gene. In addition, the possibility that women with breast cancer represent sporadic cases within hereditary cancer families must also be considered. F inally, the occurrence of BRCA1/2 variants of uncertain significance, often missense mutations, further complicates the risk assessment. In some of th ese instances, extending testing to relatives can be helpful to clarify res ults. When hereditary breast cancer cannot be ruled out, individuals may st ill be at increased risk for cancer and therefore need to obtain appropriat e surveillance. The process of genetic counseling is critical both before a nd after resting to ensure that patients understand the potential medical a nd psychosocial implications of testing and are aware of available options and resources, A multidisciplinary approach ta service delivery, which incl udes clinicians in genetics and oncology, can facilitate patients' decision making and provide continued access To information and support. J Clin Onc ol 19:2555-2565. (C) 2001 by American Society of Clinical Oncology.