—Breast cancer (BC) remains a health challenge in Iraq, with patients presenting at younger ages and advanced stages. While gene fusions, particularly ETV6-NTRK3, are established oncogenic drivers in subtypes like secretory breast carcinoma (SBC), their prevalence within the Iraqi population remains unexplored. This study aimed to detect the ETV6-NTRK3 gene fusion in Iraqi patients with BC to define its diagnostic specificity and clinicopathological correlates. Formalin-fixed paraffin-embedded tissue blocks from 60 women (aged 20–50 years) diagnosed with BC were collected. Samples were classified into three equal groups: SBC, Invasive Carcinoma of no special type, and invasive lobular carcinoma (n = 20 for each). The ETV6-NTRK3 fusion was detected using fluorescence in situ hybridization with a dual-color break-apart probe. The ETV6-NTRK3 fusion was detected exclusively in the SBC, with a prevalence of 100% (19/19 successfully scored cases), while it was absent in all scored cases of other groups, yielding a positive predictive value of 100% and a negative predictive value of 100%. Fusion-positive SBC tumors were associated with clinicopathological features: they were exclusively low to intermediate histological grade (Grades I-II) and predominantly presented at early pathological stages (Stage I-II: 84.2%). The fusion-positive cases were 93 times more likely to present with an early stage of disease compared with fusion-negative cases (odds ratio: 93.33; 95% confidence interval: 16.15–539.19). In conclusion, the ETV6-NTRK3 fusion may be a definitive molecular hallmark of SBC in Iraqi patients, and could demonstrate perfect diagnostic specificity and association with a less aggressive phenotype.
