Embedding germline genetic testing into African oncology care: Early results from the Genetic Cancer Families (GenCAF) program.

10572 Background: Breast cancer outcomes in sub-Saharan Africa are marked by early onset, advanced stage at diagnosis, and high mortality. Although prior studies demonstrate a high burden of inherited cancer susceptibility variants in African populations, access to ancestry-informed genetic counseling and testing remains limited due to infrastructure constraints and poor integration into routine oncology care. The GenCAF program was developed to translate prior genomic evidence from Nigeria into a scalable, clinically embedded cancer genomics implementation model in African settings. Methods: Consecutive breast cancer patients were prospectively enrolled and offered genetic counseling and testing regardless of age or family history. Germline testing was performed using the Color Hereditary Cancer Test (Color Health Inc). Counseling and result disclosure were delivered by locally trained oncology nurses or breast health specialists using a structured protocol. Clinical and tumor characteristics were correlated with genetic findings. The program was designed for scalability across English- and French-speaking sites. Results: Among 263 participants, 235 unrelated index breast cancer cases underwent germline testing. Overall, 43.0% (101/235) had a reportable germline finding, including 21.7% (51/235) with pathogenic or likely pathogenic (P/LP) variants and 21.3% (50/235) with variants of uncertain significance (VUS). Among genes present in ≥5% of cases with variant calls, VUS were most frequent in APC, ATM, PALB2, PMS2 , and BRCA2 , with several moderate-penetrance DNA repair genes exhibiting disproportionately high VUS burden, representing key candidates for future reclassification as African-ancestry reference data and gene–environment context expand. P/LP variants were most common in BRCA1 (n = 22), BRCA2 (n = 13), ATM (n = 4), and PALB2 (n = 4). P/LP carriers tended to be diagnosed before age 30 (13.7% vs 7.6%) and were more frequently diagnosed with advanced-stage disease (stage III–IV, 30.6%). Mean age did not differ overall; however, BRCA1 P/LP carriers had an earlier onset (mean age 40.1 years). Conclusions: These findings support integrating germline cancer genetics into routine breast cancer care in Africa through a scalable, nurse-led counseling model. The substantial VUS burden underscores the need for ancestry-informed interpretation and future reclassification efforts incorporating population-specific and environmental data. Planned implementation of point-of-care next-generation and long-read sequencing will further strengthen local diagnostic capacity and enable sustainable, locally driven precision prevention and oncology through risk-informed care. Age Group (yrs) P/LP (%) VUS (%) <30 13.7 7.6 30–39 15.7 23.9 40–49 23.5 23.4 50–59 27.5 26.6 ≥60 15.6 19.0