The Accuracy of Clinical Criteria to Predict Mutations in BRCA1- and BRCA2-Related Hereditary Breast and Ovarian Cancer Syndrome

Abstract

The Hereditary Breast and Ovarian Cancer (HBOC) Clinic located in Winnipeg accepts province-wide referrals to assess cancer risk and provide testing for mutations in BRCA1 and BRCA2 when indicated. Given the economic realities of public health care, a limited number of patients can be offered full gene testing. Manitoba has developed fourteen eligibility criteria based on personal and family history of breast and ovarian cancer that are thought to identify patients with at least a 10% chance of having a mutation. In this retrospective clinic-based study, we evaluate the association between these criteria and mutation frequency to determine which characteristics are statistically associated with BRCA1 and BRCA2 mutations. Information from hospital and lab records was collected for 429 probands tested between 1995 and 2010. Twenty-one percent of probands tested through the HBOC Clinic were found to have a disease-causing BRCA1 or BRCA2 mutation. Consistent with other studies, multiple tumor diagnoses and a strong family history of breast/ovarian cancer were the characteristics most strongly associated with the finding of mutations. Ethnicity of the Manitoba population in relation to BRCA1 or BRCA2 mutation frequency was also explored. The recurrent mutations found in the study population partially reflected the ethnic composition of the Manitoba population. All of the criteria examined in this study are achieving ≥10% mutation detection rate, but some re-evaluation is recommended to explore broadening criteria based on personal history of tumors and to adjust ethnic-specific screening by adding a Mennonite and dropping one of the Eastern European founder mutations.