Abstract P1-08-07: Predisposing germline mutations in a clinic based breast cancer (BC) population

Background: Evaluation of women with BC for germline mutations associated with hereditary breast and ovarian cancer (HBOC) has become increasingly common due to its impact on management. Guidelines for genetic evaluation indicate testing for cases with early onset, triple negative disease or family cancer history. However, the majority of breast cancer occurs in patients without these high risk characteristics. The prevalence of mutations associated with HBOC has not been well characterized in this population. Methods: We performed a cross sectional study using DNA from blood samples from consecutive new invasive BC patients seen at the Dana-Farber Cancer Institute (01/01/2010 to 07/31/2102) who consented to research. Subjects were otherwise unselected. Mutations in 25 cancer genes were identified using a next generation sequencing based panel. Germline sequence variations and large rearrangements were classified for pathogenicity. Results: 456 samples from eligible subjects were included. The mean age of BC diagnosis was 50 years. Mutations were found in 51 women, 49 of which were associated with breast cancer (10.8%, 95% CI 8.1-14.0). BRCA1/2 mutations were found in 6.6% [95% CI 4.5-9.2%] while mutations in other BC-associated genes were found in 4.4% [95% CI 2.7-6.7%], particularly CHEK2 (2.2%, 95% CI 1.1, 4.0). Of the 49 women with BC-related mutations, 21 (43%) had BC diagnosed after age 45. In univariate analyses, age at diagnosis, Ashkenazi Jewish ancestry, triple negative histology and family BC/ovarian cancer (OC) history were associated with BRCA1/2 mutations, but no factors were significantly associated with mutations in other genes. Among 261 women with no FDR/SDR with BC/OC, 26 (10.0%) had a mutation. Nineteen mutations (10 BRCA1/2 ) were found in the 256 women (7.4%) who had not had previous genetic testing. Conclusions: In a single academic institution, 11% of new breast cancer patients had a germline mutation in a breast cancer predisposition gene: 6.6% were in BRCA1/2 . The elevated prevalence compared to population-based series may reflect the practice composition of academic centers, which often attract women younger at BC diagnosis. In an academic practice with an active cancer genetics program, 10 women with BRCA1/2 and 9 with other mutations had not had genetic testing. Expanded testing identifies additional predisposing mutations, the utility of which are being defined for the care of breast cancer patients and their families. Citation Format: Garber JE, Tung NM, Elkin EP, Allen BA, Singh NU, Wenstrup R, Hartman A-R, Winer EP, Lin NU. Predisposing germline mutations in a clinic based breast cancer (BC) population. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P1-08-07.