Abstract P4-06-06: Frequency of mutations in multi-gene panel testing of 3,011 breast cancer patients

Objectives: Here, we describe the characteristics of 3,011 individuals with a self-reported diagnosis of breast cancer who received a multi-gene panel genetic test for hereditary cancer risk. Methods: These 3,011 patients were referred physician order for a multi-gene, next generation sequencing panel for hereditary cancer risk. Analysis was limited to 19 genes associated with hereditary breast and ovarian cancer (ATM, BARD1, BRCA1, BRCA2, BRIP1, CDH1, CHEK2, EPCAM, MLH1, MSH2, MSH6, NBN, PALB2, PMS2, PTEN, RAD51C, RAD51D, STK11, TP53). All patient demographic information was collected via a self-reported online health history questionnaire. Results: In this cohort, the median reported age at breast cancer diagnosis was 49.3. Overall, 360 pathogenic or likely pathogenic variants were identified and reported. A total of 344 individuals were found to carry a single pathogenic mutation in one of the 19 genes analyzed, and 8 individuals were found to carry two concurrent pathogenic mutations in different genes. Notably, 173 of the 360 mutations identified were reported in the BRCA1 and BRCA2 genes (48.1%), yielding an overall BRCA1 and BRCA2 mutation carrier rate of 5.7%. Additionally, 12.2% of the cohort reported having bilateral breast cancer. The mutation carrier rate amongst these individuals was 15.0% (50/334), 60.8% of the mutations found in these individuals were in BRCA1 or BRCA2, and the average age at breast cancer diagnosis was 49.4 (43.3 amongst mutation carriers). In the entire cohort, a pathogenic mutation was identified in 15 of the 19 genes analyzed. Conclusion: In summary, the overall mutation carrier rate in this cohort for breast and ovarian cancer risk genes was 11.7% (352/3,011). Taken together, these data support the recommendation that all patients with breast cancer should undergo germline testing for hereditary cancer risk. Citation Format: Zhou AY, van den Akker J, Zimmer A, McFadden W. Frequency of mutations in multi-gene panel testing of 3,011 breast cancer patients [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P4-06-06.