Simple SummaryBreast cancer (BC) in adolescents and young adults (AYA) has unique biological qualities, but the details of these features remain unclear, and treatment options are comparable to those of other age groups. In this study, we identified a gene that demonstrates a strong association with patient prognosis solely in AYA patients, despite the fact that its expression does not differ by age group. Although this gene,GALNT1, has no prognostic significance in whole BC, when examined in AYA BC, highGALNT1was significantly associated with worse survival. Furthermore, highGALNT1expression was found to be an independent factor for survival among several clinical features of AYA patients. Finally, highGALNT1BC is associated with increased EMT, angiogenesis, and protein secretion in AYA patients, but not in the elderly. We report the clinical relevance of theGALNT1gene in AYA BC.AbstractIt is well established that genetic information differs amongst the adolescent and young adult population (AYA) and older patients. Although several studies on genetic information have been conducted, no current prognostic biomarker exists to help differentiate survival outcomes amongst AYA patients. The GALNT family of genes have been associated with several cancer etiologies, such as the Tn antigen and epithelial-mesenchymal transition (EMT); however, the clinical significance ofGALNT1expression in breast cancer (BC) remains unclear. We investigated the clinical relevance ofGALNT1expression in BC using two large independent cohorts. We found that, although triple-negative BC (TNBC) had the highestGALNT1expression compared to ER-positive/HER2-negative BC,GALNT1levels in BC were not associated with clinical aggressiveness, including histological grade, AJCC stage and N-category, and patient survival, consistently in both the METABRIC and GSE96058 cohorts. There was also no biological difference between low- and high-GALNT1expression BC, as analyzed by hallmark gene sets via gene set enrichment analysis (GSEA). Further, no significant difference was found inGALNT1expression levels among AYAs and older patients. However, highGALNT1expression was associated with significantly worse survival in AYA patients, in both cohorts. Furthermore, highGALNT1expression was found to be an independent factor among several clinical features, including subtype, histological grade, AJCC T and N-category, in AYA patients. In both cohorts, BC with highGALNT1expression demonstrated low levels of CD8+T-cell infiltration, but not other anti-cancerous or pro-cancerous immune cells. Finally, high levels ofGALNT1BC demonstrated increased EMT, angiogenesis, and protein secretion in the AYA population, but not in older patients. In conclusion, our findings demonstrate thatGALNT1expression was found to be associated with angiogenesis and EMT, and may have potential as prognostic biomarker, specifically in AYA patients.