Abstract Background: Although African ancestry is not included in the NCCN guidelines for identifying women with invasive breast cancer who may benefit from genetic testing, African American women (AAW) are at increased risk of being diagnosed at a young age and/or with triple negative breast cancer, both factors that do meet NCCN criteria for genetic testing. Because AAW represent a frequently underserved population, we evaluated the utilization and results of germline testing of cancer predisposition genes in AAW with invasive breast cancer. Methods: 546 self-described AAW with invasive breast cancer enrolled in the Clinical Breast Care Project from 2001-2017). Eligibility status for genetic testing was assessed using the NCCN guidelines version 1.2019. In patients without clinical panel testing performed and with an available genomic DNA sample, targeted sequencing across 94 cancer predisposition genes was performed. Variants were classified as pathogenic, likely pathogenic, uncertain significance (VUS), likely benign or benign using ClinVar. Results: 60% of the patients were eligible for genetic testing of which 37% of underwent clinical testing. Within the high-risk women who pursued clinical testing, the mutation frequency was 13% and included mutations in ATM (n=2), BRCA1 (n=7), BRCA2 (n=5) and TP53 (n=1). High-risk women who were tested only in the research setting had a mutation frequency of 9% including BRCA1 (n=2) and BRCA2 (n=2) and single carriers of mutations in BLM, CHEK2, MLH1, MUTYH, PALB2, PMS2 and RECQL4. Within the 111 women who did not meet NCCN criteria, the mutation frequency was 5% with mutations in BRCA2 (n=3), PMS2 (n=1), SBHD (n=1) and TSC2 (n=1). Six women had previously unreported variants in BRCA1, BRCA2, TP53, ALK and RB1 and 29% of the women had VUS in genes including BRCA1 and BRCA2. Conclusions: Under current NCCN guidelines, the majority of AAW with invasive breast cancer were eligible for genetic testing; however, translating eligibility into pursuit of germline testing remains a challenge. For example, 33% of the high-risk women underwent clinical testing and 40% of the mutation carriers within the high-risk group were detected in the research setting. Furthermore, 5% of low-risk women, not currently eligible for genetic testing, were mutation carriers. In addition, while the majority (66%) of mutations detected were in BRCA1 or BRCA2, multi-gene testing allowed for an additional 50% of mutation carriers to be identified. Because identification of germline mutations may alter patient management and prevent secondary cancers, it is critical to identify and address barriers, such as evolving NCCN guidelines, cost, and patient preference, to testing and optimize the selection of AAW for genetic testing. The views expressed in this abstract are those of the author and do not reflect the official policy of the Department of Army/Navy/Air Force, Department of Defense, or U.S. Government. Citation Format: Leann A. Lovejoy, Seth K. Rummel, Craig D. Shriver, Rachel E. Ellsworth. Germline testing in African American women with invasive breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 621.