What is the summary, etiology, clinical features, diagnostic workup, standard of care and treatment, and prognosis of Neuroendocrine (NE) tumors of the breast?

From the Guidelines

Neuroendocrine tumors of the breast are rare malignancies that arise from neuroendocrine cells in the breast tissue. Summary: Neuroendocrine tumors of the breast are typically slow-growing and have a relatively good prognosis, but can be aggressive in some cases, as noted in studies such as 1. Etiology: The exact cause of neuroendocrine tumors of the breast is unknown, but they are thought to arise from neuroendocrine cells in the breast tissue, possibly due to genetic mutations or hormonal influences, similar to other neuroendocrine tumors 1. Clinical Features: Patients with neuroendocrine tumors of the breast may present with a palpable breast mass, nipple discharge, or breast pain, and the tumors are often estrogen receptor-positive and progesterone receptor-positive, as discussed in 1. Diagnostic Workup: Diagnosis is typically made by core needle biopsy or excisional biopsy, with immunohistochemical staining for neuroendocrine markers such as synaptophysin, chromogranin, and estrogen receptor, as recommended in 1. Standard of Care and Treatment: Treatment for neuroendocrine tumors of the breast usually involves a multidisciplinary approach, including surgery, radiation therapy, and hormone therapy, with surgical options including lumpectomy or mastectomy, depending on the size and location of the tumor, and hormone therapy with tamoxifen 20mg daily for 5-10 years may be recommended for patients with estrogen receptor-positive tumors, as suggested in 1. Prognosis: The prognosis for neuroendocrine tumors of the breast is generally good, with a 5-year survival rate of around 80-90%, but the prognosis can vary depending on the tumor size, grade, and presence of lymph node metastases, and regular follow-up with a healthcare provider is essential to monitor for recurrence and manage any side effects of treatment, as noted in 1.

From the Research

Summary

• Neuroendocrine (NE) tumors of the breast are a heterogeneous group of tumors, accounting for less than 1% of all NE tumors 2.
• They are classified into neuroendocrine tumors (NETs) (G1, G2) and neuroendocrine carcinomas (NECs) (small cell carcinoma, large cell neuroendocrine carcinoma) according to the 5th edition of the WHO Classification of Breast Tumors in 2019 2.

Etiology

• The exact pathogenesis of NE tumors of the breast is still unclear, and further exploration is required to determine the tissue origin of these tumors 2.
• It is hypothesized that primary breast neuroendocrine carcinoma differentiates from the epithelial cells during the carcinogenesis process 3.

Clinical Features

• Clinical features and morphology are not helpful to distinguish NE tumors of the breast from other subtypes of breast cancer 4.
• The clinical features and radiological characteristics of NE tumors of the breast are not different from those of other types of breast cancer 5.

Diagnostic Workup

• The diagnosis of NE tumors of the breast relies on the presence of a neuroendocrine architecture and the expression of neuroendocrine markers (chromogranin A and/or synaptophysin) 5.
• Immunohistochemistry markers for neuroendocrine differentiation, mainly chromogranin and synaptophysin, should be routinely used to confirm the diagnosis 4.
• The diagnosis is mainly dependent on the exclusion of other extra-mammary organs based on clinical, radiological, and pathological data 3.

Standard of Care and Treatment

• The treatment of NE tumors of the breast is still based on invasive breast carcinomas of no special type (IBCs-NST), and without any difference from invasive carcinoma with NE features 2.
• Early stage tumors are usually treated with the same strategy used for the other types of invasive breast cancer, including anthracycline- and taxane-based regimens 4.
• Adjuvant chemotherapy is recommended for patients with a Ki-67 index of ≥10%, and hormonal treatment appears to be feasible in patients who are positive for estrogen and/or progesterone receptor 6.
• A multimodality therapeutic strategy can be considered on an individual basis, with chemotherapy, endocrine therapy, peptide receptor radionuclide therapy, radiation therapy, surgery, or a combination of the above 4.

Prognosis

• The prognosis of NE tumors of the breast remains unclear, while the prognosis for NECs is significantly poorer than invasive breast carcinomas of no special type (IBCs-NST) 2.
• The prognosis of non-small cell primary NE tumors of the breast seems to improve as the amount of mucinous component increases in the tumor specimen 3.
• The clinical outcome is still poorly defined due to discordant results 5.