Clinicopathological characteristics and tumor-detected genetic variations in Chinese patients with ductal carcinoma in situ of the breast.

OBJECTIVES: This study investigates relationships among the multi-omics features of ductal carcinoma in situ (DCIS) and provides evidence to support non-invasive classification and personalized treatment strategies. METHODS: A large cohort of patients with DCIS (n = 224) was established for integrated analyses encompassing genomic alterations, clinicopathological characteristics, histopathological morphology, and mammographic features. RESULTS: Analysis of the mutational landscape identified TP53 as the most frequently altered gene (53.13%), followed by PIK3CA (38.84%) and KMT2C (27.67%). Distinct molecular subtypes showed unique mutational profiles. TP53 mutations were particularly prevalent in the triple-negative (91.67%) and HER2-enriched (81.96%) subtypes, whereas PIK3CA (53.06%) and GATA3 (28.57%) mutations were more common in luminal subtypes. Significant associations were also observed between recurrent gene variations and clinical exposure factors, including age, reproductive history, and family history of cancer. Alterations in key signaling pathways varied considerably across the morphological and mammographic characteristics of DCIS. For instance, alterations in the RTK/RAS pathway were more frequently detected in comedo-type DCIS and were significantly associated with fine pleomorphic and fine linear/fine linear branching microcalcifications, which typically show linear or segmental distributions. CONCLUSION: The observed associations among genomic, morphological, and mammographic features indicate that imaging characteristics can reflect the underlying biological heterogeneity of DCIS. These results represent an important step toward the non-invasive assessment of tumor biology and may facilitate more individualized treatment approaches for patients with DCIS.