Breast Neuroendocrine Carcinoma: Molecular Insights Beyond Histology.
Breast neuroendocrine carcinomas show far more frequent TP53 mutations than similar breast cancers
Breast Neuroendocrine Carcinoma: Molecular Insights Beyond Histology.
Primary breast neuroendocrine carcinomas (neuroendocrine carcinomas) are rare, high-grade malignancies that are frequently grouped with invasive breast carcinomas with neuroendocrine differentiation (invasive breast carcinomas with neuroendocrine differentiation), despite uncertain biological equivalence.
We sought to define the clinicopathologic, immunophenotypic, and genomic features of breast neuroendocrine carcinomas and to determine whether they represent a biologically distinct entity.
We performed a retrospective analysis of 24 primary breast neuroendocrine carcinomas and compared them with 28 grade-matched IBC-NEDs.
TP53 mutations are far more common in neuroendocrine carcinomas than invasive breast carcinomas with neuroendocrine differentiation
Breast neuroendocrine carcinomas were predominantly estrogen receptor (estrogen receptor)-negative/human epidermal growth factor receptor-2-negative (63%) and frequently exhibited small cell morphology.
Immunophenotypically, neuroendocrine carcinomas demonstrated diffuse neuroendocrine marker expression and frequent loss of Rb protein (93%), consistent with RB pathway disruption.
Compared with invasive breast carcinomas with neuroendocrine differentiation, neuroendocrine carcinomas showed significantly lower estrogen receptor expression and reduced GATA3 positivity.
Breast neuroendocrine carcinomas is characterized by a distinct clinicopathologic and molecular profile compared with grade-matched invasive breast carcinomas with neuroendocrine differentiation, defined by frequent TP53 and RB1 alterations, RB pathway disruption, and limited response to neoadjuvant therapy.
These findings support classification of breast neuroendocrine carcinomas as a biologically distinct subtype and highlight potential avenues for biomarker-driven therapeutic strategies in this rare malignancy.