Current Understanding of Neuroendocrine Tumors of Breast - An Integrated Review

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.