Primary Neuroendocrine Tumor of the Breast: Current Understanding and Future Perspectives

Abstract

Primary neuroendocrine carcinoma of the breast (NECB) is characterized with heterogeneity, rarity, and poor differentiation, which is probably an underestimated subtype of breast cancer, including small cell NECs and large cell NECs. The diagnostic criteria for NECB have been constantly updated as the disease changes and the understanding increases. According to the latest WHO Classification, primary neuroendocrine neoplasm (NEN) of the breast consists of well-differentiated neuroendocrine tumors (NET), extremely aggressive neuroendocrine carcinomas (NEC) as well as invasive breast cancers of no special type (IBCs-NST) with neuroendocrine differentiation. The accurate diagnosis of NECB remains a challenge for its low incidence, which needs multi-disciplinary methods. For the rarity of the disease, there is a lack of large samples and prospective clinical research. For these invasive tumors, there are no standardized therapeutic guidelines or norms, and the treatment often refers to nonspecific breast cancer. In addition, the prognosis of such patients remains unknown. In 2003, the World Health Organization (WHO) listed NECB as an independent entity for the first time, while few features of NECB were clarified. In this review, it presents the WHO Classification, clinicopathologic characteristics, diagnosis, treatment, and prognosis of these patients. In addition, it summarizes the latest studies on molecular features of NECB, aiming to provide new therapeutic perspectives for the disease.

Mixed neuroendocrine carcinoma consisting of small cell neuroendocrine carcinoma, metaplastic carcinoma, and invasive ductal carcinoma in the breast: A case report and review of the literature

“…It is our venture to speculate whether the development of neuroendocrine carcinoma components is related to metaplastic carcinoma and whether it is a speci c type of metaplastic carcinoma that has not been reported. We consider whether this conjecture can be veri ed with the help of molecular assays and other methods, and it has been shown that a certain percentage of PIK3CA mutation rate exists in both NECB and MpBC [1,5] .…”

“…Neuroendocrine carcinoma of the breast (NECB) is a rare clinical cancer with neuroendocrine morphology, immunophenotype, and high-grade cytological features, including small cell neuroendocrine carcinoma (SCNEC) and large cell neuroendocrine carcinoma (LCNEC). NECB is characterized by heterogeneity, rarity, and poor differentiation [1] . To date, the mechanisms, molecular changes, clinicopathological features, and prognosis of NECB are not well understood.…”

Primary neuroendocrine breast cancer—an unusual occurrence

“…The histological origin of BNEN is still unclear but the latest data postulates two theories. Some researchers propose that these tumours arise due to differentiation in breast cancer cells as NE cells have not been found in breast tissues, while another school of thought suggests NE cell proliferation in breast parenchyma in isolated clusters may be related to some precancerous states [ 10 ].…”

“…The differential diagnosis for these primary carcinomas is essentially metastasis from NECs at other sites. Presence of DCIS and the absence of tumours in other organs in radiology help in clinching the diagnosis of primary NEC of the breast [ 10 ]. In the current case, DCIS was not found, however, there were no symptoms or radiological findings suggesting metastasis from other organs.…”

Case report: Neuroendocrine breast carcinoma with a germline EGFR T790M mutation

“…There is a lack of high-quality data regarding therapeutic options in patients with disease progression of neuroendocrine carcinoma of the breast ( 58 ). Neuroendocrine carcinoma follows a more aggressive course than ductal carcinoma ( 57 , 59 ).…”