Abstract Background: Next generation sequencing and broadened genetic testing guidelines have made it possible to perform multi-gene testing upfront for patients at risk for hereditary breast cancer. Breast surgeons and oncologists are ideally situated at the forefront of cancer treatment to initiate these tests since results can impact treatment decisions. This study evaluates the utility of multi-gene testing in a multidisciplinary breast practice. Methods: Data was collected retrospectively from 500 consecutive patients who underwent multi-gene panel testing July 2013 – September 2014. Patients were evaluated at time of visit if they met criteria for genetic testing based on NCCN guidelines. Results: Most patients had no prior genetic testing; 28.8% of patients had previous negative BRCA1 and BRCA2 (BRCA1/2) tests. All patients had a personal and/or family history of breast or ovarian cancer. All patients were evaluated with a multi-gene panel consisting of a minimum of 5 breast-cancer related genes (BRCA1, BRCA2, PTEN, TP53, and CDH1) and most (68.0%) had extended panel testing of up to 43 cancer-associated genes. Pathogenic mutations were identified in 32 (6.4%) patients. The majority of patients (79.0%) were not found to carry any mutations, while 16.2% had at least one genetic variant of uncertain significance. Of the patients with pathogenic mutations, 37.5% had a mutation in BRCA1/2 while most patients had mutations in non-BRCA1/2 genes. PatientMutationPersonal History of CancerBreast CancerAge at Breast Cancer DxType of Breast CancerOther Cancer1ATMyes47DCIS 2ATMyes77IDC 3BARD1, CHEK2yes39IDC 4BRCA1yesno Ovarian, age 515BRCA1yes46IDC 6BRCA2yes42IDC 7BRCA2yes76ILCOvarian, age 558BRCA2yes43DCIS 9BRCA2yes46IDC 10BRCA2yes54IDC 11BRCA2yes36ILC 12BRCA2yes38ILC 13BRCA2yes64IDC 14BRCA2yes35IDC 15BRCA2nono 16CHEK2yes35not availableThyroid, age 6017CHEK2yes66IDC 18CHEK2yes65DCIS 19CHEK2yes44IDC 20CHEK2yes43IDC 21CHEK2nono 22MRE11Anono 23MSH2nono 24MUTYHyes41DCIS 25MUTYHyes53DCIS 26MUTYHnono 27NBNyes72IDC 28PALB2yes59IDC 29PALB2yes42IDC 30PALB2yes53IDC 31RAD51Cyesno Ovarian, age 6532TP53yes46DCIS The majority of patients with mutations had a personal history of cancer including breast, ovarian, and thyroid cancer. There was no significant difference between age of breast cancer diagnosis and having a BRCA1/2 mutation compared to having a non-BRCA gene mutation. The majority of gene-positive patients with cancer had hormone-positive invasive ductal carcinoma(IDC) while only two patients had triple negative breast cancer. Compared to patients with BRCA1/2 mutations, patients with non-BRCA mutations were more likely to have a family history of non-breast or ovarian cancer(58.3% vs 90%, respectively, p=0.0735). Conclusions: Multi-gene panel testing will identify more patients with risk of breast and ovarian cancer than routine BRCA1/2 testing alone, and may have an impact on screening for other cancers as well. Obtaining a thorough personal and family cancer history is necessary to provide optimal counseling and screening. Citation Format: Kapoor NS, Curcio LD, Patrick M, Swisher J, West JD, Banks K. Multi-gene panel testing and the cancers identified in patients at risk for hereditary breast cancer. [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 PD7-05.