Abstract 7402: High frequency of germline mutations among breast cancer patients in Jamaica

Abstract Breast cancer (BCa) is the most common cancer among Jamaican women, with 60-70% presenting at advanced stages (III or IV). Incidence rates are slightly lower (43.1 per 100, 000) than global rates (47.8 per 100, 000) and mortality rates are notably higher (18.1 per 100, 000 versus 13.6 per 100, 000). This study investigated germline testing in Jamaican women with BCa to examine clinicopathologic associations and to compare the utility of two genetic testing panels within this population. A retrospective, cross-sectional study was conducted on 178 Jamaican women with pathologically confirmed BCa at 8 hospital sites during 2018 - 2024. Cancer data extracted from patients' medical records included BCa type, cancer surgeries performed, metastatic sites, tumor stage, molecular markers (ER, PR, HER2, Ki67) and documentation of family history of cancer. Germline genetic testing was performed using comprehensive multigene panel tests from either Invitae (n=126) or Blueprint Genetics (n=52). The Invitae panel assessed 84 genes associated with hereditary cancer syndromes, while the Blueprint panel examined 160 genes. Both panels included core BCa susceptibility genes (BRCA1, BRCA2, PALB2, CHEK2, ATM). Data underwent quality control measures including removal of duplicates, standardization of formats, appropriate handling of missing values, and validation of outliers prior to statistical analysis using STATA 18 Software. The mean age was 44.5±10.5 years with most patients having at least one variant classification (36.5%). Just over 40% and 34% had Luminal A/B and triple negative molecular subtypes respectively, and 36% had advanced stage. Variants classified as pathogenic or likely pathogenic (P/LP) were identified in 15.7% of cases. P/LP status was significantly associated with multiple variant status (p<0.001) with 57.1% of cases with P/LP status having two or more gene variants overall when compared to 42.4% with VUS status. Of the 75 genes examined amongst the cases, 10.7% had mutations in BRCA2. Thirty-two of the 255 variants classified were unique P/LP variants. Of these variants, BRCA2 had the most positive (30.6%); c.3109C>T p.(Gln1037*) being the most common P/LP variant overall (8.3%). Other high frequency variants were c.303T>G p.(Tyr101*) in BRCA1 and c.258+2T>C in SBDS. A greater proportion of patients carried P/LP variants when tested by Blueprint Genetics (19%) in contrast to 14% when tested by Invitae. No genetic variants were identified for 32.6% of participants. Our findings reveal a high frequency of germline mutations in Jamaican BCa patients. This supports the need for implementing germline testing as part of treatment planning and to ensure the utilization of targeted therapies. Further investigations of broader gene panels beyond the traditional BCa susceptibility genes may be warranted for better understanding of the germline mutation landscape in this population. Citation Format: Patrick Roberts, Rory Thompson, Richard Shaw, Alison Ayoub, Imani Hewitt, Derria Cornwall, Natalie Guthrie-Dixon, Camille Ragin, Simone Ann Marie Badal. High frequency of germline mutations among breast cancer patients in Jamaica [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 7402.