Age-stratified analysis of invasive lobular carcinoma reveals comparable clinicopathological and molecular features across age groups

Young-onset breast cancer (YOBC) is generally associated with aggressive behavior and poor prognosis. Young-onset invasive lobular carcinoma (Y-ILC) is rare, and its clinicopathological and molecular features remain unclear. This study aimed to clarify its characteristics using public datasets. Clinical, pathological, survival and genomic data for invasive lobular carcinoma (ILC) were collected from The Cancer Genome Atlas, Molecular Taxonomy of Breast Cancer International Consortium and Memorial Sloan Kettering Cancer Center databases. Patients were classified into three age groups: Y-ILC (≤ 45 years), middle-aged ILC (M-ILC, 46–69 years) and older ILC (O-ILC, ≥ 70 years). Comparative analyses of clinicopathological features, survival outcomes and genetic profiles were performed among the three cohorts. Y-ILC accounted for only 5.4% of YOBC cases, confirming its rarity. Among 402 ILC cases, 30 (7.5%) were Y-ILC, 259 (64.4%) M-ILC and 113 (28.1%) O-ILC. No significant differences in clinicopathological parameters were observed among the three age groups. Survival analysis revealed significant differences in 5- and 10-year overall survival and restricted mean survival time among the groups, with O-ILC showing markedly poorer outcomes. Y-ILC tended to show higher frequencies of BRCA1 and CASP8 mutations, while copy number alterations in FGF4, FGF19 and CCND1 increased progressively with age. Y-ILC is rare and clinically comparable to ILC in older age groups, showing broadly similar molecular profiles with subtle age-related differences. Although YOBC is generally viewed as high-risk, Y-ILC did not demonstrate inferior survival; rather, survival deterioration was confined to the older cohort.