Translate this page into:
Current Understanding of Neuroendocrine Tumors of Breast - An Integrated Review
-
Received: ,
Accepted: ,
How to cite this article: Singhal BM, Kewlani V. Current Understanding of Neuroendocrine Tumors of Breast - An Integrated Review. Int J Recent Surg Med Sci. 2025:11(e014). doi: 10.25259/IJRSMS_40_2025
Abstract
Neuroendocrine tumors of the breast are a rare heterogeneous subgroup that is still not well understood. They can occur in both pure and mixed forms. The incidence of Breast neuroendocrine neoplasms (BrNEN) is <1% of all NENs reported in the body. Malignant neuroendocrine neoplasm (NEN) of the breast is also known as Neuroendocrine Breast Cancer (NEBC) and has an incidence rate of 0.3-0.5%, which is 0.1-5% of all breast cancers. The BrNEN expresses positive staining for Chromogranin (CgA), Synaptophysin (Syn), Neurone specific Enolase (NSE), and CD56, which are usually negative in invasive breast cancers (IBCs). Most subtypes of BrNEN/NEBC are Hormone Receptor positive and HER-2 neu negative. They may belong to either the luminal A or B molecular subtypes and are considered a distinct subtype of luminal breast cancer, mainly affecting post-menopausal women. Immunohistochemical (IHC) markers for ER, PR, and AR are positive in most well-differentiated neuroendocrine tumors (NETs) and >50% of poorly differentiated NETs.
Currently, due to a lack of specific guidelines, management of BrNEN is the same as Invasive Ductal Carcinoma (IDC), which is based on tumor node metastasis (TNM) staging and prognostic factors-based protocols. In this review, we have aimed to summarize our current understanding of BrNENs and particularly the NEBC, regarding their molecular characteristics, diagnostic criteria, current treatment strategies, as well as future perspectives in BrNENs. Advances in understanding the molecular characteristics of these tumors might be helpful in further improvement in the diagnostic accuracy, determination of actual incidence, as well as development of standard protocols for precision-targeted therapy.
Keywords
Breast cancer
BrNEN
Carcinoid breast
NEBC
Neuroendocrine breast carcinoma
INTRODUCTION
Neuroendocrine Neoplasms (NENs) are a rare, heterogeneous group of tumors that arise from neuroendocrine cells. These cells are present in various organs of the body, and have been reported from multiple sites like central nervous system (CNS), respiratory tract, larynx, gastro-intestinal tract (GIT), thyroid, Skin, uro-genital system, and breast.[1,2]
Breast cancer with a neuroendocrine (NE) subtype was first reported by Feyrter & Hartmann in 1963.[3] It was followed by the reporting of eight cases of “Primary Carcinoid of the breast” by Cubilla & Woodruff in 1977.[4] Furthermore, in 1982, based on silver staining and ultra-structural evaluation, Argyrophil carcinoma of the breast was reported.[5] It was followed by the identification of positive chromogranin A (CgA) expression in the normal mammary parenchyma by Bussolati et al in 1985, which gave definitive proof of NE differentiation in breast carcinoids.[6]
The incidence of Breast Neuroendocrine Neoplasm (BrNEN) is <1% of all NENs reported in the body.[7] Malignant NEN of the breast is also known as NE Breast Cancer (NEBC) and has an incidence rate of 0.3-0.5%, which is 0.1-5% of all breast Cancers. 30% percent of invasive breast cancers (IBCs), like mucinous and solid papillary carcinomas, may also have NE differentiation.[8,9] The variation in the reported incidence rate may be due to constantly changing histological and diagnostic criteria over the years. Another reason is that routine immunohistochemical (IHC) staining for NE markers is not done in all specimens of breast cancer.
This review aims to summarize our current understanding of BrNENs and particularly the NEBC, regarding their molecular characteristics, diagnostic criteria, current treatment strategies, as well as future perspectives in Breast NENs.
Histogenesis
The two most acceptable hypotheses regarding the origin of BrNENs are stated below:
-
1.
-
2.
There is early differentiation of neoplastic stem cells into both NE and epithelial cells. This is supported by the fact that benign NETs of the breast are not found, and studies report that NE cells are clonally related to malignant epithelial cells. The existence of both exocrine–endocrine differentiation within the same tumor also suggests a common origin from mammary stem cells. This is also supported by molecular studies, identifying both NE cells and exocrine cells in poorly differentiated carcinoma of the breast.[7,11,13-17]
PATHOLOGY & CHANGES IN WHO DIAGNOSTIC CRITERIA
Sapino et al in 2000 initially defined the diagnostic and histogenetic features of the various types of “NE differentiated carcinomas of the breast,” as a spectrum of breast tumors largely composed of NE cells to be distinguished from “breast carcinomas not otherwise specified (NOS) with NE differentiation.”[18]
Following this report, World Health Organization (WHO) Classification of Breast And Reproductive System Tumours, (3rd) Edition in 2003 recognized BrNENs as a distinctive epithelial origin neoplasm with morphological features similar to NE tumors of gastrointestinal tract and pulmonary origin, and >50% of tumor cells expressing NE markers (CgA and Synaptophysin-Syn). Based on morphology, degree of differentiation, and grade, BrNENs were subdivided into three subtypes: small cell/oat cell carcinoma, large cell NE carcinoma, and solid NE carcinoma.[10,19,20]
In 2012, WHO classification of breast tumours, 4th edition, modified the 50% threshold for IHC expression of CgA, and Syn was removed. This classification defined BrNEN as “Tumors with similar morphological characteristics to gastrointestinal and lung NE tumors and expressing NE markers to varying degree.” BrNENs were subtyped into well-differentiated NET, poorly differentiated NET/small cell carcinoma, and invasive carcinoma with NE differentiation (included special types: hypercellular mucinous carcinoma and solid papillary carcinoma).[8,10,20-21]
Again in 2019, WHO classification of breast tumors, 5th Edition, due to difficulties in differentiating between breast cancer with NE features and NEBC. The criteria for BrNEN were also reclassified into two subtypes: well-differentiated NET and poorly-differentiated NEBC (included small cell and large cell NEC).[8,10,20,22,23]
As per 2019 WHO Classification of Breast tumors, 5th Edition, the criteria for defining a tumor as Pure BrNEN are:
-
morphological characteristics similar to gastrointestinal and lung NE tumors
-
> 90% of tumor cells express NE Markers CgA and Syn.
If the <10% cells express NE markers, it should be classified as IBC with a focal NE pattern. Specimens with 10-90% cells expressing NE markers should be diagnosed with IBC along with NET/NEC.[10]
Histopathological features as enumerated in the WHO classification of Breast tumors, (5th) Edition, are the presence of dense cells arranged in large or small nests along with trabeculae split by thin collagenous fibrovascular stroma and numerous small fine vessels. Cells may be fusiform, oval to polygonal, plasmatoid, or spindle-shaped with granular eosinophilic cytoplasm and eccentric nuclear placement. There may be tumor nests floating in large mucinous pools. Small cell NEC has invasive growth, with dense distribution of uniformly small cells, unclear cellular boundaries, meager cytoplasm, high nuclear/cytoplasm ratio, and vague nucleoli. In large cell NECs, cells are big with abundant cytoplasm, polymorphic nuclei, and coarse chromatin. Both small and large cell NECs usually have marked mitoses, with areas of focal necrosis and lymphatic emboli that are common. In primary BrNEN/NEBC, additional foci of ductal carcinoma in situ (DCIS) may be present. Mitotic count is the principal consideration for grading these tumors. Most of the Breast NETs are Grade 1 or 2 as per Nottingham Criteria for breast cancer. Some authors have classified breast NETs as G1, G2, and G3, which have not yet been recognized by the WHO.[10]
Some authors find it more appropriate to consider breast NETs as a subtype of INCs‐no specific type (IBCs‐NST), as morphology, prognosis, and treatment of NEBC are similar to IBC-NST. Breast NET often lacks classic carcinoid-like features (ribbons, cords, and rosettes). In the diagnosis of primary breast NET, it is important to exclude metastases from other sites and breast cancer with NE features.[1,10,24]
Immuno-histochemical (IHC) features
The BrNEN expresses positive staining for CgA, Syn, Neurone-specific Enolase (NSE), and CD56, which are usually negative in IBC.[20] CgA and Syn are the most sensitive and specific NE Markers, and Syn in particular is significantly more sensitive than CgA. The NSE as well as CD56 are less sensitive and less specific markers, limiting their usefulness to screening for NE differentiation rather than in diagnosis. Recent studies have found new biomarkers like Insulinoma-associated protein (INSM) transcriptional repressor 1 (INSM1), ISL LIM homeobox 1 (ISL1), and secretagogin (SECG), having sensitivities similar to or marginally less than that of CgA and Syn.[10,20,25,26]
To verify origin, primarily from breast positive expression of certain site-specific makers like GATA-3, Mammoglobin, and GCDFP-15 is helpful. Negative expression for Thyroid transcription factor 1 (TTF1) (Lung), Caudal-related homeobox transcription factor 2 (CDX2) Gastro-intestinal tract (GIT), Paired box protein 8 and Paired box protein 6 (PAX8/PAX6) (GIT) and Glypican 3 (Hepatic) helps in excluding extra-mammary sites.[20,24,27,28]
Most of the subtypes of BrNEN/NECB are hormone receptor positive and HER-2 neu negative. They may belong to either the luminal A or B molecular subtypes and are considered to be a distinct subtype of luminal breast cancer mainly affecting post-menopausal women, by some authors. estrogen receptor (ER), progesterone receptor (PR), androgen receptor (AR) IHC markers are positive in most well-differentiated NETs and >50% of poorly differentiated NET.[24,29,30]
Molecular features
As BrNEN and NECB are not common, there is limited literature on molecular and mutational profiling of these tumors. Studies have shown that NECB has a different mutational profile than hormone-positive breast cancers, having a lower rate of PIK3CA mutation.[20,31-33] It has been reported that NECB has a significantly lower frequency of PIK3CA and TP53 mutations in comparison to Luminal cancers.[8,34]
In one study, various molecular markers were evaluated, and it was found that 52% of BrNEN are of Luminal A and 48% are of the Luminal B subtype. They have reported that BrNEN are ER (+ve) in 100%, and PR (+ve) in 89%, GATA3 (+ve) in 98%, FOXA1 (+ve) in 96%, and CDK 8/18 (+ve) in 98%.[30] In other studies, several genes like FOXA1, TBX3, GATA3, and ARIDIA with a high rate of mutation were also reported.[10,33,35]
Research by Veranic et al has highlighted that predictive expression of TROP-2, FOLR1, and H3K36Me3 was detected in different subsets of tumors, which has the potential for the development of novel targeted therapies in some patients with breast NECs.[36]
CLINICAL PRESENTATION & DIAGNOSIS
The clinical presentation of BrNEN is mostly very similar to breast cancer, including a breast mass, nipple or skin retraction, blood-stained nipple discharge, ulceration, etc. It is more common in post-menopausal women of 60-70 years of age and rarely seen in men.[37-40] Majority of patients have metastases at time of diagnosis, and most common metastatic sites are bone, lung & pleura, liver, brain, bone marrow, skin, and even adrenals.[34,41-45] Most cases are not associated with carcinoid syndrome, and approximately 40% of them are associated with regional lymph node metastases.[22,34,44,46,47] Well-differentiated NET may produce hormones, but poorly differentiated tumors are essentially non-functional. There are occasional reports of BrNEN causing ectopic ACTH, norepinephrine, and calcitonin-related syndrome.[48-50] Differential diagnoses include neuroendocrine tumors metastatic to the breast, Merkel cell carcinoma, lymphoma, melanoma, adenoid cystic cancer, and triple-negative breast cancer (TNBC).[10,11,22]
BrNEN does not have any distinctive characteristics, and imaging features are nonspecific. USG shows a hypoechoic irregular solid mass with irregular margins and hypervascularity. No posterior enhancement or cystic area can be seen.[1,39,51] Mammography revealed a round, oval, lobulated masses hyperdense mass with irregular margins. Microcalcification is usually absent.[10,20,51-53] Magnetic Resonance Imaging (MRI) also suggests a breast mass with irregular margins, with heterogenous mild enhancement and washout kinetics consistent with malignant lesions.[20,39] Contrast-enhanced computed tmography (CECT) scan of chest and abdomen has a limited role, mainly to rule out metastases from other primary sites, if suspected.[8,20] Positron emission tomography (PET CT) with gallium-labelled somatostatin analog is useful in assessing well-differentiated NET. But for poorly differentiated NECBs and small cell carcinomas, 18 Fludeoxyglucose (FDG) PET scan is more useful. It is employed in case of uncertainty between primary and secondary disease and evaluation of metastatic spread.[7,20,54,55]
As BrNEN can be diagnosed only by morphological and IHC characteristics of the tumor. Fine needle aspiration cytology (FNAC) is not suitable, and only core needle biopsy provides adequate tissue for evaluation.
TREATMENT
There are no specific guidelines for the management of BrNEN, as these tumors are not so common. Currently, it is the same as Invasive ductal carcinoma (IDC), which is based on TNM staging and prognostic factors. Like IBCs, prognostic factors taken into consideration for stage-wise treatment planning are tumour size, lymph node involvement, distant metastasis, expression of ER, PR, & Her-2Neu, Ki67 index, genotype & nuclear Grade, age, menopausal status, and performance status of the patient. Both adjuvant and neoadjuvant chemotherapy for locally invasive disease has been found to be effective in decreasing the risk of local and distal recurrence and improving survival.[1,11,30,55-58]
For localized disease, surgery is the primary modality, and choice of surgical procedure depends on the location of the tumor as well as on the clinical stage. In most cases standard surgical option is Modified Radical Mastectomy (MRM), but early stage tumors can be corrected with Breast Conservation Surgery (BCS) also.[30,59] Based on histopathological analysis of the surgical specimen, adjuvant chemotherapy or chemoradiation is planned. For Metastatic Disease, Palliative chemotherapy is the main modality.
BrNEN are uncommon tumors, so most of the chemotherapy protocols are based on data from small cell lung cancer chemotherapy studies. Presently, for well-differentiated BrNENs and IBCs with neuro-endocrine differentiation, anthracycline-based and taxane-based chemotherapy is recommended. For poorly-differentiated, small cell, and large cell NEBCs, platinum-etoposide regimens are recommended.[1,17,53,60-62]
In unusual instances of HER-2 Neu over-expression in NECB, treatment with trastuzumab was found to be very effective. There are reports of partial and long-term response to anti-HER-2 Neu therapy (trastuzumab, pertuzumab, TDM-1, and ADC), when given both as adjuvant treatment or in metastatic disease.[63-70]
As the majority of BrNEN are ER PR positive, Hormonal therapy with aromatase inhibitors has also been reported to be effective in certain instances in HR-positive BrNEN.[1,37,61,71,72]
Although there are conflicting opinions on the benefits of radiotherapy (RT) in BrNEN, adjuvant RT to the chest wall and regional lymph node regions is being advised as per management protocols for IBC.[10,30,73,74]
Most of the reports suggest that, stage by stage, NEBCs are associated with poorer prognosis in comparison to IBC. A population-based study from the SEER database also reported worse overall survival (OS) and disease-specific survival (DSS) in NEBC.[38] Among subtypes, poorly-differentiated NE carcinomas fare worse in comparison to other subtypes.[35]
Future therapeutic options
As many studies have reported significant response to CDK 4/6 inhibitors in combination with aromatase inhibitors or fuvestrant in advanced or metastatic HR positive IBCs, it is being considered for use in metastatic BrNEN. Promising results have also been reported with tyrosine kinase inhibitors such as lapatinib, neratinib, and tucatinib in HER-2 Neu-positive advanced breast cancer, so they can be utilized in HER-2 Neu-positive BrNEN also.[10,75,76] A systematic review found panzopanib to be efficacious in metastatic and locally advanced NENs.[77] Genomic studies have reported alterations in PIK3CA/PTEN pathway in 46% small cell carcinoma of breast; therefore, targeting the PI3K/AKT/mTOR pathway by PI3K inhibitors like alpelisip and mTOR inhibitors like everolimus seems to be a potential modality for HR positive BrNENs due to their proven efficacy in metastatic IBC.[1,20,30,78-80] In gut and pancreatic NETs, somatostatin analogs have proven efficacy, and BrNENs have also been found to be positive for somatostatin receptors (SSTR2A and SSTR5) on IHC. So BrNEN are a potential target for such therapy, but in clinical studies, these were not found to be effective.[30,81,82] Studies using radiolabeled Somatostatin analogues (90Y- DOTATOC AND 177Lu-DOTATOC) for Peptide Receptor Radionucleotide Therapy (PRRT) have reported promising results.[10,30,83,84]
In a study for therapeutic biomarkers, Vranic et al detected TROP-2 proteins and FOLRI1, making them a potential target for antibody drug conjugates like sacituzumab govitecan for TROP-2 positive patients and farletuzumab & mirvetuximab soravtansine for FOLRI1 positive patients.[10,20,36,85] In patients with FGFR aberrations, FGFR inhibitors like pemigatinib, infigratinib and erdafitinib may prove beneficial, as they are being used in cholangiocarcinoma and urothelial carcinoma. Studies suggest that bevacizumab and PARP inhibitors can also be useful in NEBC.[10,20]
Immune checkpoint inhibitors have been found to be beneficial in high-grade NEN from other primary sites, so they also have a potential use in PD-LI-positive NENs.[20] Additionally, NENs with gene mutations in TP53, KRAS, and HRAS can also benefit from immune checkpoint inhibitor therapy.[10,86]
CONCLUSION
BrNENs are a rare heterogenous subgroup of breast tumors, which is still not well understood despite continuing progress in WHO classification in defining and diagnosing this entity. They can occur in both pure form and mixed form. It is important to exclude metastases from other primary sites, as well as Breast Cancer with NE features, to avoid misdiagnosis. Currently, due to a lack of specific guidelines, management of BrNEN is the same as IDC, which is based on TNM Staging and Prognostic factors-based protocols. These are uncommon tumors, so most of the chemotherapy protocols are based on data from studies on small cell lung cancer and NET of other sites. Advances in understanding the molecular characteristics of these tumors might be helpful in further improvement in the diagnostic accuracy, determination of actual incidence, as well as development of standard protocols and precision targeted therapy.
Ethical approval
The Institutional Review Board has waived the ethical approval for this study
Declaration of patient consent
Patient’s consent not required as there are no patients in this study.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
Use of artificial intelligence (AI)-assisted technology for manuscript preparation
The authors confirm that there was no use of artificial intelligence (AI)-assisted technology for assisting in the writing or editing of the manuscript and no images were manipulated using AI.
References
- Primary neuroendocrine neoplasms of the breast: Still open issues. Front Endocrinol (Lausanne). 2021;11:610230.
- [CrossRef] [PubMed] [PubMed Central] [Google Scholar]
- Nothing but NET: A review of neuroendocrine tumors and carcinomas. Neoplasia. 2017;19:991-1002.
- [CrossRef] [PubMed] [PubMed Central] [Google Scholar]
- Uber Die Carcinoide Wuchsform Des Carcinoma Mammae, Insbesondere Das Carcinoma Solidum (Gelatinosum) Mammae [On the Carcinoid Growth Form of the Carcinoma Mammae, especially the Carcinoma Solidum (Gelatinosum) Mammae] Frankf Z Pathol.. 1963;73:24-39.
- [PubMed] [Google Scholar]
- ‘Carcinoid’ tumours of the breast: The morphological spectrum of argyrophil carcinomas. Histopathology. 1982;6:549-6.
- [CrossRef] [PubMed] [Google Scholar]
- Chromogranin-reactive endocrine cells in argyrophilic carcinomas (“carcinoids”) and normal tissue of the breast. Am J Pathol. 1985;120:186-92.
- [PubMed] [PubMed Central] [Google Scholar]
- Neuroendocrine neoplasms of the breast: The latest WHO classification and review of the literature. Cancers (Basel). 2021;14:196.
- [CrossRef] [PubMed] [PubMed Central] [Google Scholar]
- Management of neuroendocrine breast carcinoma (NEBC): Review of literature. Oncol Rev. 2024;18:12114.
- [CrossRef] [PubMed] [PubMed Central] [Google Scholar]
- Primary neuroendocrine carcinoma of breast. J Cytol. 2011;28:91-2.
- [CrossRef] [PubMed] [Google Scholar]
- Neuroendocrine neoplasms of the breast: Current insights and future directions. Cancer Rep (Hoboken). 2024;7:e70059.
- [CrossRef] [PubMed] [PubMed Central] [Google Scholar]
- Neuroendocrine carcinoma of the breast: Current evidence and future perspectives. Oncologist. 2016;21:28-32.
- [CrossRef] [PubMed] [PubMed Central] [Google Scholar]
- Neuroendocrine cells associated with neuroendocrine carcinoma of the breast: Nature and significance. J Clin Pathol. 2012;65:699-703.
- [CrossRef] [PubMed] [Google Scholar]
- Neuroendocrine differentiation and prognosis in breast adenocarcinoma. Histopathology. 2002;40:215-22.
- [CrossRef] [PubMed] [Google Scholar]
- Primary mammary small-cell carcinoma: A molecular analysis of 2 cases. Hum Pathol. 2001;32:753-7.
- [CrossRef] [PubMed] [Google Scholar]
- Electron microscopy and immunostaining of the normal breast and its benign lesions A search for neuroendocrine cells. Histol Histopathol. 1987;2:73-7.
- [PubMed] [Google Scholar]
- Expression of neuroendocrine markers in different molecular subtypes of breast carcinoma. Biomed Res Int. 2014;2014:408459.
- [CrossRef] [PubMed] [PubMed Central] [Google Scholar]
- Locally-advanced primary neuroendocrine carcinoma of the breast: Case report and review of the literature. World J Surg Oncol. 2013;11:128.
- [CrossRef] [PubMed] [PubMed Central] [Google Scholar]
- Expression of the neuroendocrine phenotype in carcinomas of the breast. Semin Diagn Pathol. 2000;17:127-37.
- [PubMed] [Google Scholar]
- Pathology and genetics. In: Tumors of the breast and female genital organs. WHO Classification of Tumors Series. Lyon, France: IARC Press; 2003. p. :32-34.
- [Google Scholar]
- Primary neuroendocrine tumor of the breast: Current understanding and future perspectives. Front Oncol. 2022;12:848485.
- [CrossRef] [PubMed] [PubMed Central] [Google Scholar]
- WHO classification of tumours of the breast (4th ed). Lyon: IARC Press; 2012. p. :62-63.
- WHO Classification of Tumours— Breast Tumours (5th ed). Lyon: IARC Press; 2019. p. :155-159.
- The 2019 World Health Organization classification of tumours of the breast. Histopathology. 2020;77:181-5.
- [CrossRef] [PubMed] [Google Scholar]
- Li JJX, Tse GM. Neuroendocrine tumor. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/breastmalignantneuroendocrine.html. Accessed June 6th, 2025.
- Clinical routine application of the second-generation neuroendocrine markers ISL1, INSM1, and secretagogin in neuroendocrine neoplasia: Staining outcomes and potential clues for determining tumor origin. Endocr Pathol. 2020;31:401-10.
- [CrossRef] [PubMed] [PubMed Central] [Google Scholar]
- INSM1 is a novel prognostic neuroendocrine marker for luminal B breast cancer. Pathology. 2021;53:170-8.
- [CrossRef] [PubMed] [Google Scholar]
- Neuroendocrine neoplasm of the breast presenting as a liver metastasis: A rare diagnostic challenge. Cureus. 2021;13:e16860.
- [CrossRef] [PubMed] [PubMed Central] [Google Scholar]
- Neuroendocrine tumors of the breast. Arch Pathol Lab Med. 2017;141:1577-81.
- [CrossRef] [PubMed] [Google Scholar]
- Neuroendocrine neoplasms of the breast: A review of literature. Virchows Arch. 2024;485:197-212.
- [CrossRef] [PubMed] [PubMed Central] [Google Scholar]
- Novel mutations in neuroendocrine carcinoma of the breast: Possible therapeutic targets. Appl Immunohistochem Mol Morphol. 2015;23:97-103.
- [CrossRef] [PubMed] [Google Scholar]
- Comparison of the mutational profiles of neuroendocrine breast tumours, invasive ductal carcinomas and pancreatic neuroendocrine carcinomas. Oncogenesis. 2022;11:53.
- [CrossRef] [PubMed] [PubMed Central] [Google Scholar]
- The genetic landscape of breast carcinomas with neuroendocrine differentiation. J Pathol. 2017;241:405-19.
- [CrossRef] [PubMed] [PubMed Central] [Google Scholar]
- Comprehensive clinical and molecular analyses of neuroendocrine carcinomas of the breast. Mod Pathol. 2018;31:68-82.
- [CrossRef] [PubMed] [Google Scholar]
- Neuroendocrine tumours of the breast: A genomic comparison with mucinous breast cancers and neuroendocrine tumours of other anatomic sites. J Clin Pathol. 2022;75:10-7.
- [CrossRef] [PubMed] [PubMed Central] [Google Scholar]
- Potential novel therapy targets in neuroendocrine carcinomas of the breast. Clin Breast Cancer. 2019;19:131-6.
- [CrossRef] [PubMed] [Google Scholar]
- Invasive neuroendocrine carcinoma of the breast: A population-based study from the surveillance, epidemiology and end results (SEER) database. BMC Cancer. 2014;14:147.
- [CrossRef] [PubMed] [Google Scholar]
- Breast neuroendocrine tumor arising in the axilla of a man: A case report. J Med Case Rep. 2022;16:467.
- [CrossRef] [PubMed] [PubMed Central] [Google Scholar]
- Primary neuroendocrine carcinoma of the breast: Clinical, imaging, and histologic features. AJR Am J Roentgenol. 2014;203:W221-30.
- [CrossRef] [PubMed] [Google Scholar]
- Invasive neuroendocrine carcinoma of the breast: A distinctive subtype of aggressive mammary carcinoma. Cancer. 2010;116:4463-73.
- [CrossRef] [PubMed] [Google Scholar]
- Cutaneous spread of primary neuroendocrine breast carcinoma with apocrine differentiation. J Eur Acad Dermatol Venereol. 2015;29:1440-1.
- [CrossRef] [PubMed] [Google Scholar]
- Multinodular cutaneous spread in neuroendocrine tumor of the breast : An unusual presentation. Am J Clin Dermatol. 2007;8:379-83.
- [CrossRef] [PubMed] [Google Scholar]
- Validation of prognostic significance of the proposed uniform classification framework in neuroendocrine neoplasms of the breast. Breast Cancer Res Treat. 2021;186:403-15.
- [CrossRef] [PubMed] [PubMed Central] [Google Scholar]
- Neuroendocrine cancer of the breast: A rare entity. J Clin Med. 2020;9:1452.
- [CrossRef] [PubMed] [PubMed Central] [Google Scholar]
- A population-based analysis of outcomes for small cell carcinoma of the breast by tumor stage and the use of radiation therapy. Springerplus. 2015;4:138.
- [CrossRef] [PubMed] [PubMed Central] [Google Scholar]
- The epidemiology and survival of extrapulmonary small cell carcinoma in South East England, 1970-2004. BMC Cancer. 2009;9:209.
- [CrossRef] [PubMed] [PubMed Central] [Google Scholar]
- Neuroendocrine breast tumours: Breast cancer or neuroendocrine cancer presenting in the breast? Breast. 2014;23:120-7.
- [CrossRef] [PubMed] [Google Scholar]
- Adrenocorticotropin production by a mammary carcinoma. Cancer. 1981;47:1823-7.
- [CrossRef] [PubMed] [Google Scholar]
- Norepinephrine-producing tumors of bilateral breasts: A case report. Cancer. 1978;41:2002-7.
- [CrossRef] [PubMed] [Google Scholar]
- Secretion of immunoreactive calcitonin by human breast carcinomas. Br Med J. 1975;4:197-9.
- [CrossRef] [PubMed] [Google Scholar]
- Solid neuroendocrine breast carcinoma: Mammographic and sonographic features in thirteen cases. Chin J Cancer. 2012;31:549-56.
- [CrossRef] [PubMed] [PubMed Central] [Google Scholar]
- Neuroendocrine differentiated breast carcinoma: Imaging features correlated with clinical and histopathological findings. Eur Radiol. 2003;13:788-93.
- [CrossRef] [PubMed] [Google Scholar]
- Primary neuroendocrine neoplasms of the breast: Case series and literature review. Cancers (Basel). 2020;12:733.
- [CrossRef] [PubMed] [PubMed Central] [Google Scholar]
- The evolution of neuroendocrine tumor treatment reflected by ENETS guidelines. Neuroendocrinology. 2018;106:357-65.
- [CrossRef] [PubMed] [PubMed Central] [Google Scholar]
- ENETS consensus guidelines for the standards of care in neuroendocrine tumors: Radiological, nuclear medicine and hybrid imaging. Neuroendocrinology. 2017;105:212-44.
- [CrossRef] [PubMed] [Google Scholar]
- Surgery of the primary tumor in metastatic breast cancer: Closing the barn door after the horse has bolted? J Clin Oncol. 2006;24:2694-6.
- [CrossRef] [PubMed] [Google Scholar]
- Management of neuroendocrine carcinomas of the breast: A rare entity. Oncol Lett. 2011;2:887-90.
- [CrossRef] [PubMed] [Google Scholar]
- Primary large-cell neuroendocrine carcinoma of the breast occurring in a pre-menopausal woman. Breast Care (Basel). 2015;10:281-3.
- [CrossRef] [PubMed] [PubMed Central] [Google Scholar]
- Customizing local and systemic therapies for women with early breast cancer: The St gallen international consensus guidelines for treatment of early breast cancer 2021. Ann Oncol. 2021;32:1216-35.
- [CrossRef] [PubMed] [PubMed Central] [Google Scholar]
- A case of primary neuroendocrine breast carcinoma that responded to neo-adjuvant chemotherapy. Front Med. 2015;9:112-6.
- [CrossRef] [PubMed] [Google Scholar]
- Primary neuroendocrine tumors of the breast: Two case reports and review of the literature. J Med Case Rep. 2020;14:41.
- [CrossRef] [PubMed] [PubMed Central] [Google Scholar]
- Primary neuroendocrine carcinoma of the breast: A case report of liver and lymph node metastases after eight years from diagnosis. Breast J. 2020;26:505-7.
- [CrossRef] [PubMed] [Google Scholar]
- HER2-positive neuroendocrine breast cancer: Case report and review of literature. Breast Care (Basel). 2016;11:424-6.
- [CrossRef] [PubMed] [PubMed Central] [Google Scholar]
- Rare human epidermal growth factor receptor 2 (HER-2)-positive neuroendocrine carcinoma of the breast: A Case report with 9-year follow-up. Am J Case Rep. 2020;21:e925895.
- [CrossRef] [PubMed] [PubMed Central] [Google Scholar]
- Pertuzumab, trastuzumab, and docetaxel for HER2-positive metastatic breast cancer (CLEOPATRA): End-of-study results from a double-blind, randomised, placebo-controlled, phase 3 study. Lancet Oncol. 2020;21:519-30.
- [CrossRef] [PubMed] [Google Scholar]
- Adjuvant pertuzumab and trastuzumab in early HER2-positive breast cancer. N Engl J Med. 2017;377:122-31.
- [CrossRef] [PubMed] [PubMed Central] [Google Scholar]
- Trastuzumab emtansine for residual invasive HER2-positive breast cancer. N Engl J Med. 2019;380:617-28.
- [CrossRef] [PubMed] [Google Scholar]
- Trastuzumab emtansine for HER2-positive advanced breast cancer. N Engl J Med. 2012;367:1783-91.
- [CrossRef] [PubMed] [PubMed Central] [Google Scholar]
- Tucatinib, trastuzumab, and capecitabine for HER2-positive metastatic breast cancer. N Engl J Med. 2020;382:597-609.
- [CrossRef] [PubMed] [Google Scholar]
- Trastuzumab deruxtecan in previously treated HER2-positive breast cancer. N Engl J Med. 2020;382:610-21.
- [CrossRef] [PubMed] [PubMed Central] [Google Scholar]
- Solid neuroendocrine breast carcinomas: Incidence, clinico-pathological features and immunohistochemical profiling. Oncol Rep. 2008;20:1369-74.
- [PubMed] [Google Scholar]
- Small cell carcinoma of the breast: A clinicopathologic and immunohistochemical study of nine patients. Am J Surg Pathol. 2000;24:1231-8.
- [CrossRef] [PubMed] [Google Scholar]
- Tumeurs neuroendocrines primitives du sein: Mythe ou réalité? Une revue de la littérature. Bulletin du Cancer. 2018;105:431-9.
- [CrossRef] [PubMed] [Google Scholar]
- Primary small cell carcinoma of the breast: A case report. J Med Case Rep. 2017;11:290.
- [CrossRef] [PubMed] [PubMed Central] [Google Scholar]
- FDA drug approval summary: Lapatinib in combination with capecitabine for previously treated metastatic breast cancer that overexpresses HER-2. Oncologist. 2008;13:1114-9.
- [CrossRef] [PubMed] [Google Scholar]
- Neratinib plus capecitabine versus lapatinib plus capecitabine in HER2-positive metastatic breast cancer previously treated with >/= 2 HER2-directed regimens: phase III NALA Trial. J Clin Oncol. 2020;38:3138-49.
- [CrossRef] [PubMed] [PubMed Central] [Google Scholar]
- Phase-II trials of pazopanib in metastatic neuroendocrine neoplasia (mNEN): A systematic review and meta-analysis. Front Oncol. 2020;10:414.
- [CrossRef] [PubMed] [PubMed Central] [Google Scholar]
- Genetic and immunohistochemical profiling of small cell and large cell neuroendocrine carcinomas of the breast. Mod Pathol. 2022;35:1349-61.
- [CrossRef] [PubMed] [PubMed Central] [Google Scholar]
- Genomic landscape of small cell carcinoma of the breast contrasted to small cell carcinoma of the lung. Breast Cancer Res Treat. 2016;158:195-202.
- [CrossRef] [PubMed] [Google Scholar]
- Neuroendocrine breast carcinoma: A rare but challenging entity. Med Oncol. 2020;37:70.
- [CrossRef] [PubMed] [PubMed Central] [Google Scholar]
- Investigation of somatostatin receptor profile of neuroendocrine carcinomas of the breast. Pathol Res Pract. 2020;216:153066.
- [CrossRef] [PubMed] [Google Scholar]
- Somatostatin analogs in clinical practice: A review. Int J Mol Sci. 2020;21:1682.
- [CrossRef] [PubMed] [PubMed Central] [Google Scholar]
- Somatostatin receptor type 2A immunohistochemistry in neuroendocrine tumors: A proposal of scoring system correlated with somatostatin receptor scintigraphy. Mod Pathol. 2007;20:1172-82.
- [CrossRef] [PubMed] [Google Scholar]
- 177Lu-DOTATOC peptide receptor radionuclide therapy in a patient with neuroendocrine breast carcinoma and breast invasive ductal carcinoma. Clin Nucl Med. 2020;45:e232-5.
- [CrossRef] [PubMed] [Google Scholar]
- Efficacy and safety of anti-trop-2 antibody drug conjugate sacituzumab govitecan (IMMU-132) in heavily pretreated patients with metastatic triple-negative breast cancer. J Clin Oncol. 2017;35:2141-8.
- [CrossRef] [PubMed] [PubMed Central] [Google Scholar]
- Comprehensive analysis of clinicopathologic features and p53 mutation in neuroendocrine neoplasms of the breast: Experience from a large academic center. Breast Cancer Res Treat. 2022;196:463-9.
- [CrossRef] [PubMed] [PubMed Central] [Google Scholar]