Genotype-first approach to the detection of hereditary breast and ovarian cancer risk, and effects of risk disclosure to biobank participants.

Genotype-first approach allows to systematically identify carriers of pathogenic variants in BRCA1/2 genes conferring a high risk of familial breast and ovarian cancer. Participants of the Estonian biobank have expressed support for the disclosure of clinically significant findings. With an Estonian biobank cohort, we applied a genotype-first approach, contacted carriers, and offered return of results with genetic counseling. We evaluated participants' responses to and the clinical utility of the reporting of actionable genetic findings. Twenty-two of 40 contacted carriers of 17 pathogenic BRCA1/2 variants responded and chose to receive results. Eight of these 22 participants qualified for high-risk assessment based on National Comprehensive Cancer Network criteria. Twenty of 21 counseled participants appreciated being contacted. Relatives of 10 participants underwent cascade screening. Five of 16 eligible female BRCA1/2 variant carriers chose to undergo risk-reducing surgery, and 10 adhered to surveillance recommendations over the 30-month follow-up period. We recommend the return of results to population-based biobank participants; this approach could be viewed as a model for population-wide genetic testing. The genotype-first approach permits the identification of individuals at high risk who would not be identified by application of an approach based on personal and family histories only.

Adherence Patterns to National Comprehensive Cancer Network Guidelines for Referral of Women With Breast Cancer to Genetics Professionals.

OBJECTIVE: Genetic predisposition is responsible for 5% to 10% of breast cancer. The National Comprehensive Cancer Network (NCCN) established guidelines delineating appropriate candidates for genetic counseling. This study aims to determine referral patterns for genetic counseling in women who met such guidelines. MATERIALS AND METHODS: Utilizing an institutional tumor registry, patients from an academic oncology program who met a subset of NCCN guidelines for genetic referrals between 2004 and 2010 were identified (breast cancer diagnosis ≤50 y without a known BRCA mutation). A retrospective chart review was conducted. Statistics were analyzed using SAS version 9.2. RESULTS: A total of 314 patients were identified and 107 (34.1%) were referred for genetic counseling. Median age at diagnosis was younger for those referred versus not referred (43 and 46 y; P<0.0001). Women were more likely referred with a family history suspicious for an inherited cancer syndrome (67.3% vs. 36.2%; P<0.0001). There was no difference in stage at diagnosis, insurance, or race among women referred. Those patients who choose prophylactic contralateral mastectomy were likely to have been referred for genetic counseling (63.6% vs. 36.4%, P<0.0001). Among patients referred, 77.6% consulted with a genetics counselor, 95.2% underwent genetic testing, and 16.5% had a BRCA mutation. CONCLUSIONS: Genetic counseling and testing is being underutilized in women who meet NCCN referral guidelines. Age and family history were noted to be predictive of referral for genetic evaluation. Further research is needed to determine additional factors that may impact not only referral rates but subsequent care for women with possible genetic predispositions to cancer.