Clinical implications of universal germline testing in breast cancer patients in an Arab population: The Jordanian Exploratory Cancer Genetics (Jo-ECAG) study

e22535 Background: Germline genetic testing (GGT) for breast cancer (BC) has implications for surgical decision-making, treatment selection, clinical follow-up and cascade testing. As uptake of GGT increases globally, it is important to examine its impact on clinician decision-making, particularly in different ethnic groups. Methods: The Jo-ECAG Study consisted of unselected, newly diagnosed cancer patients (pts) from a single center in Jordan. Pts were classified as meeting (in criteria, IC) or not meeting (out of criteria, OOC) National Comprehensive Cancer Network (NCCN) v.1.2020 GGT criteria. Pts underwent a 84 gene test with clinician-reported outcomes collected >2 months post GGT. Analysis was limited to pts with BC. Pts with one PGV in a gene associated with autosomal recessive inheritance (“carriers”) were excluded from overall PGV count. Blank responses were considered uninformative. Descriptive statistics and Fisher’s exact test were employed. Results: 1648 (21 male) Arabic pts with BC, 36% metastatic, with a mean age at diagnosis of 50.5 were tested; 67% were IC. 212 PGVs were identified in 202 (12%) pts, with a significantly higher rate in IC vs. OOC pts (14% vs. 8%, p=0.0002). PGVs were most common in BRCA1/2 (4%), APC I1307K (4%), and other BC-associated genes such as ATM, CHEK2, PALB2 and TP53 (collectively, 3%). 2% of pts were carriers and 57% had uncertain results. Among pts with PGVs and informative responses (Table), 18% had changes to treatment (11% OOC) and 82% to surveillance/follow up (16% OOC) based on GGT results. Genetic counseling and/or GGT was recommended for relatives of >90% of PGV and carrier pts. No changes to treatment or follow-up were made for pts with negative or uncertain results. Conclusions: 1 in 8 Jordanian BC pts had a PGV identified, with a similar breakdown of PGVs observed in other ethnic cohorts, aside from a higher percentage of APC I1307K. Both treatment and surveillance/follow-up decisions were impacted by GGT results. Appropriately treatment or management was not escalated for pts with negative or uncertain results. [Table: see text]