ArticleJCO precision oncology2026
Breast Neuroendocrine Carcinoma: Molecular Insights Beyond Histology.
Article in JCO precision oncology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Authors and funding
11 authors.
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Abstract
purposePrimary breast neuroendocrine carcinomas (NECs) are rare, high-grade malignancies that are frequently grouped with invasive breast carcinomas with neuroendocrine differentiation (IBC-NED), despite uncertain biological equivalence. We sought to define the clinicopathologic, immunophenotypic, and genomic features of breast NEC and to determine whether they represent a biologically distinct entity.
methodsWe performed a retrospective analysis of 24 primary breast NECs and compared them with 28 grade-matched IBC-NEDs. Clinicopathologic features, treatment response, and outcomes were evaluated. Immunohistochemical profiling included neuroendocrine and breast lineage markers and retinoblastoma (Rb) expression. Targeted tumor-normal next-generation sequencing was performed in a subset of NEC (n = 10) and IBC-NED (n = 7) to characterize genomic alterations and pathway-level differences.
resultsBreast NECs were predominantly estrogen receptor (ER)-negative/human epidermal growth factor receptor-2-negative (63%) and frequently exhibited small cell morphology. Despite radiographic response to neoadjuvant chemotherapy, no patients achieved pathologic complete response. Immunophenotypically, NECs demonstrated diffuse neuroendocrine marker expression and frequent loss of Rb protein (93%), consistent with RB pathway disruption. Compared with IBC-NED, NECs showed significantly lower ER expression and reduced GATA3 positivity. Genomically, NECs were enriched for
conclusionBreast NEC is characterized by a distinct clinicopathologic and molecular profile compared with grade-matched IBC-NED, defined by frequent
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