Population genetic screening for hereditary breast and ovarian cancer in at-risk patients: A novel testing and prevention model for community hospitals reveals high mutation rates rurally.

Abstract

1575 Background: Genetic testing for at risk non-cancer patients continues to increase (Guo F, et al Cancer 2020). We identified a high risk of familial breast and ovarian cancer in rural eastern North Carolina, and created a systematic approach for genetic screening, counseling and testing. Methods: A family history questionnaire was designed to assess for the risk for hereditary breast and ovarian cancer (HBOC) using NCCN guidelines, and used at key intake points within the unaffected population to determine eligibility for genetic testing. First it was offered at the time of all mammograms. Second, we offered it in the primary gynecology care setting to capture younger patients not participating in screening mammography. Patients meeting HBOC criteria were sent a letter and two phone calls to schedule genetic counseling. Analysis via descriptive statistics. Results: 3000 rural women screened using our systematic approach to genetic risk assessment. 22.4% (673/3000) of female patients met NCCN criteria for HBOC panel testing. All offered consultation and counseling. With a backlog to see patients due to higher than expected accrual, 217 patients have completed pre-test genetic counseling, 201 completed local 19-gene panel test, and 201 had post-test counseling. Germline mutations (=>1) that predict for genetic susceptibility to cancer(s) occur in 7.8% of our screened and tested population. Currently 1 in 400 patients screened in our unaffected population carry a BRCA mutation, and 1 in 200 carry some pathogenic mutation that increases risk for HBOC. Conclusions: This rural model of screening and prevention of at risk patients for HBOC is successful at detecting pathogenic mutations in unaffected patients before they are diagnosed with cancer. Interestingly, the rate of positivity in the unaffected population (meeting criteria) is as high as the known breast cancer population rate of germline mutations (5-10%), validating the use of testing guidelines with our model. Discovering this susceptibility before a cancer diagnosis resulted in appropriate high risk management with prevention and risk reduction strategies. We plan to expand this model to the male screening population in 2021, and streamline genetic assessment and testing for the larger population at risk by engaging more rural primary care clinics over time to increase testing compliance. We also plan to consider broader gene panels as newer mutations become linked to HBOC. Clinical trial information: UMCIRB 19-001052.