Primary neuroendocrine breast cancer, how much do we know so far?

Primary neuroendocrine cancer of the breast (NECB) is an extremely rare tumor. In 2003, the World Health Organization (WHO) recognized this category with three well-described subtypes: small cell, large cell, and carcinoid-like carcinoma; very few peer-review publications based on the WHO definition were encountered in the literature, and we conducted a literature search to investigate the reported incidence, diagnosis, prognosis, hormone receptor status, and treatment options for this rare tumor. Confirming the breast as an origin of neuroendocrine tumor represents a challenge. The diagnosis is mainly dependent on the exclusion of other extra-mammary organs based on clinical, radiological, and pathological data. Except for the very rare type small cell carcinoma, estrogen and progesterone receptors were reported to be expressed in 90 and 83% of NECB, respectively. It is hypothesized that primary breast neuroendocrine carcinoma differentiates from the epithelial cells during the carcinogenesis process; the prognosis of non-small cell primary NECB seems to improve as the amount of mucinous component increases in the tumor specimen. Management similar to interventions utilized to manage the usual ductal-type carcinoma has been attempted in the past, such as chemotherapy and hormonal therapy; however, due to the rarity of the tumor, none of the published studies are randomized nor do they have a large number of patients. Additionally, none of reports analyzed NECB based on its distinct subtypes. These limitations make recommendations largely based on anecdotal and small observatory studies and call for the need for further research in this extremely rare tumor.