Cancer Risk Models: Translating Family History into Clinical Management

BRCA1 and BRCA2 mutation carriers have a very high lifetime risk for breast or ovarian cancer. Because strategies to reduce these risks are effective (1), identifying appropriate individuals for genetic testing is very important. During genetic counseling, a professional obtains a detailed 3-generation pedigree, examines it to determine potential inheritance patterns, and decides whether to recommend genetic testing. The probability that a person has a BRCA1 or BRCA2 mutation is 1 factor in deciding about genetic testing and medical management. Researchers have developed statistical models that predict the absolute risk for breast and other types of cancer and estimate the probability of finding germline mutations in cancer susceptibility genes. In this issue, Parmigiani and colleagues (2) tested the ability of 6 of these models to discriminate BRCA1 and BRCA2 mutation carriers from noncarriers. The models included in the study, as well as several others (3, 4), are in current use in cancer risk assessment programs (5).

Being systematic about estimating genetic cancer risk is important. One issue is cost. Full sequencing of BRCA1 and BRCA2 costs approximately $3000. Therefore, identifying individuals who are most likely to benefit from genetic testing is important. Accuracy is another issue. Women tend to overestimate their risk for breast cancer and their probability of having a BRCA1 or BRCA2 mutation (6). Models are useful for placing the risk of a family in context for both the patient and the clinician. Fairness is yet another issue. Adopting standard algorithms to recommend genetic testing could help to ensure fair, appropriate, and equal access to this costly but potentially life-saving technology. One strategy to ensure fairness would be to adopt a specific threshold probability of a germline mutation, above which to recommend testing for BRCA1 and BRCA2 mutations. Despite the appeal of a specific …