Multiplatform Genomic and Transcriptomic Profiling of Breast Carcinomas with an Invasive Micropapillary Component

Background/Objectives: Invasive micropapillary carcinoma (IMPC) of the breast is a rare subtype with a strong propensity for lymph node metastasis, but its molecular features remain incompletely defined. We characterized the genomic and transcriptomic features of breast carcinomas with an invasive micropapillary component. Methods: Thirteen tumors with a micropapillary component of at least 10%, including four pure IMPCs, were analyzed by targeted sequencing (n = 11), whole-exome sequencing with array comparative genomic hybridization (n = 2), and whole-transcriptome sequencing (n = 9). Alteration frequencies were compared with TCGA-BRCA across all 375 panel genes, with multiple-testing correction and a sensitivity analysis restricted to truncating and hotspot variants. Results:TP53 was the most frequently altered gene (72.7%), followed by ERBB2 amplification (45.5%); PIK3CA and GATA3 were each altered in 27.3%. Four rarely mutated genes were more frequent than in TCGA-BRCA after correction, but these differences were based on few tumors and predominantly on uncertain missense variants and were not retained under the stringent definition. Recurrent high-level amplification was concentrated in 17q12-q21, and both pure IMPCs analyzed by array comparative genomic hybridization showed 8q gain. All five tumors with panel ERBB2 amplification were HER2-positive by immunohistochemistry, and TCGA-anchored PAM50 classified all three HER2-positive transcriptomes as HER2-enriched. Fourteen fusion transcripts were detected, none recurrent. Conclusions: These findings support a heterogeneous molecular landscape characterized by established breast cancer drivers, recurrent copy-number changes involving 8q and 17q, predominantly private fusion events, and cross-platform concordance of ERBB2 amplification with HER2 protein expression and PAM50 HER2-enriched classification.