ArticleModern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc2022
Genetic and immunohistochemical profiling of small cell and large cell neuroendocrine carcinomas of the breast.
Article in Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 20 citations in OpenAlex.
- Breast Neuroendocrine Carcinoma: Molecular Insights Beyond Histology.JCO precision oncology · 2026Article
- Primary large cell neuroendocrine carcinoma of the breast with metastasis in the lymph nodes: a case report and literature review.Frontiers in oncology · 2026Article
- Emerging Breast Cancer Subpopulations: Functional Heterogeneity Beyond the Classical Subtypes.International journal of molecular sciences · 2025Review
- Mammary small cell neuroendocrine carcinomas that showed excellent pathologic response following etoposide-based neoadjuvant chemotherapy.Breast cancer research and treatment · 2025Article
- Diagnostic relevance of p53 and Rb status in neuroendocrine tumors G3 from different organs: an immunohistochemical study of 465 high-grade neuroendocrine neoplasms.Virchows Archiv : an international journal of pathology · 2025Article
- Primary neuroendocrine tumor of the breast: A case report.Oncology letters · 2025Article
- A case-based review of urachal carcinoma with mixed small cell neuroendocrine and adenocarcinoma components, with one new case report and analysis of nine published cases.Frontiers in endocrinology · 2025Review
- Neuroendocrine Neoplasms of the Breast: Current Insights and Future Directions.Cancer reports (Hoboken, N.J.) · 2024Review
- RB1 Genetic Alterations in Estrogen Receptor-Positive Breast Carcinomas: Correlation With Neuroendocrine Differentiation.Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc · 2024Article
- Defining triple-negative breast cancer with neuroendocrine differentiation (TNBC-NED).The journal of pathology. Clinical research · 2023Article
- Comprehensive analysis of clinicopathologic features and p53 mutation in neuroendocrine neoplasms of the breast: experience from a large academic center.Breast cancer research and treatment · 2022Article
Corrections and comments
- Erratum issued
Authors and funding
9 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Neuroendocrine carcinomas (NEC) of the breast are exceedingly rare tumors, which are classified in the WHO system as small cell (SCNEC) and large cell (LCNEC) carcinoma based on indistinguishable features from their lung counterparts. In contrast to lung and enteropancreatic NEC, the genomics of breast NEC have not been well-characterized. In this study, we examined the clinicopathologic, immunohistochemical, and genetic features of 13 breast NEC (7 SCNEC, 4 LCNEC, 2 NEC with ambiguous small versus large cell morphology [ANEC]). Co-alterations of TP53 and RB1 were identified in 86% (6/7) SCNEC, 100% (2/2) ANEC, and 50% (2/4) LCNEC. The one SCNEC without TP53/RB1 alteration had other p53 pathway aberrations (MDM2 and MDM4 amplification) and was immunohistochemically RB negative. PIK3CA/PTEN pathway alterations and ZNF703 amplifications were each identified in 46% (6/13) NEC. Two tumors (1 SCNEC, 1 LCNEC) were CDH1 mutated. By immunohistochemistry, 100% SCNEC (6/6) and ANEC (2/2) and 50% (2/4) LCNEC (83% NEC) showed RB loss, compared to 0% (0/8) grade 3 neuroendocrine tumors (NET) (p < 0.001) and 38% (36/95) grade 3 invasive ductal carcinomas of no special type (IDC-NST) (p = 0.004). NEC were also more often p53 aberrant (60% vs 0%, p = 0.013), ER negative (69% vs 0%, p = 0.005), and GATA3 negative (67% vs 0%, p = 0.013) than grade 3 NET. Two mixed NEC had IDC-NST components, and 69% (9/13) of tumors were associated with carcinoma in situ (6 neuroendocrine DCIS, 2 non-neuroendocrine DCIS, 1 non-neuroendocrine LCIS). NEC and IDC-NST components of mixed tumors were clonally related and immunophenotypically distinct, lacking ER and GATA3 expression in NEC relative to IDC-NST, with RB loss only in NEC of one ANEC. The findings provide insight into the pathogenesis of breast NEC, underscore their classification as a distinct tumor type, and highlight genetic similarities to extramammary NEC, including highly prevalent p53/RB pathway aberrations in SCNEC.
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