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Review
. 2021 Dec 31;14(1):196.
doi: 10.3390/cancers14010196.

Neuroendocrine Neoplasms of the Breast: The Latest WHO Classification and Review of the Literature

Yukinori Ozaki  1   2 , Sakiko Miura  3 , Ryosuke Oki  1   4 , Teppei Morikawa  3 , Keita Uchino  1
Affiliations
Review

Neuroendocrine Neoplasms of the Breast: The Latest WHO Classification and Review of the Literature

Yukinori Ozaki et al. Cancers (Basel). .

Abstract

Breast tumors with neuroendocrine (NE) differentiation comprise an uncommon and heterogeneous group of tumors, including invasive breast cancer of no special type (IBC-NST) with NE features, neuroendocrine tumors (NETs), and neuroendocrine carcinoma (NEC). The most recent World Health Organization (WHO) classification in 2019 defined neuroendocrine neoplasms (NENs) of the breast (Br-NENs) as tumors in which >90% of cells show histological evidence of NE differentiation, including NETs (low-grade tumors) and NEC (high-grade). Due to the low prevalence of these tumors and successive changes in their diagnostic criteria over the years, only limited evidence of these tumors exists, derived mainly from case reports and retrospective case series. Breast tumors with NE differentiation are usually treated like the more commonly occurring IBC-NSTs. Immunohistochemistry (IHC) of breast tumors with NE differentiation usually shows a hormone receptor (HR)-positive and human epidermal growth factor type 2 (HER2)-negative profile, so that hormonal therapy with cyclin-dependent kinase (CDK)4/6 inhibitors or other targeted agents would be reasonable treatment options. Herein, we present a review of the literature on breast tumors with NE differentiation as defined in the latest WHO 2019 classification, and discuss the clinical management of these tumors.

Keywords: classification; management; neuroendocrine carcinoma; neuroendocrine carcinoma of the breast; neuroendocrine tumor; review.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Literature flow chart of the PubMed database using terms of “breast” AND (“neuroendocrine carcinoma” OR “neuroendocrine tumors” OR “neuroendocrine differentiation”).
Figure 2
Figure 2
Summary of changes in the WHO Classification of NE tumors over the years (original figure by authors).
Figure 3
Figure 3
Morphological and immunohistochemical features of NEC of the breast. Neuroendocrine carcinoma (NEC) of the breast showing infiltrative, densely packed hyperchromatic cells with a high nuclear-to-cytoplasmic ratio. Mitotic figures are seen (arrows). (A) H & E staining (×200); (B) positive immunostaining for chromogranin A (×200) (Pictures by authors).
Figure 4
Figure 4
Morphological and immunohistochemical features of NET of the breast. Neuroendocrine tumor (NET) of the breast characterized by closely packed nests of cells with round and uniform nuclei. (A) H & E staining (×200); (B) positive immunostaining for synaptophysin (×200) (Pictures by authors).
Figure 5
Figure 5
Overview of treatment strategy for resectable Br-NEN. Treatment strategy including surgery, adjuvant systemic therapy, and radiotherapy should be considered based on recommendations for IBC-NST. Neoadjuvant systemic therapy should be considered for locally advanced disease.
Figure 6
Figure 6
Systemic therapy for recurrent or metastatic Br-NEN. Systemic therapy for recurrent or metastatic Br-NEN including chemotherapy, hormonal therapy for HR-positive disease, anti-HER2 therapy for HER2-positive disease, somatostatin analogue, peptide receptor radionuclide therapy, and other agents.
See this image and copyright information in PMC

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