Background: Neuroendocrine neoplasms (NENs) of the breast are rare, heterogeneous malignancies varying from well-differentiated neuroendocrine tumours (NETs) to poorly differentiated neuroendocrine carcinomas (NECs). Diagnosis is challenging due to histopathologic overlap with invasive breast carcinoma of no special type and the absence of consensus-based treatment guidelines. The objective of this study was to characterise the clinicopathologic spectrum, immunophenotype, management strategies and outcomes of primary breast NENs treated at a tertiary cancer centre in North India.
Methods: We retrospectively reviewed 12 histologically confirmed cases of breast NENs diagnosed between 2019 and 2024. Clinical, radiologic, histopathologic, immunohistochemical, staging, treatment and survival data were tabulated and analysed to identify any distinctive patterns, specifically clinical presentation, tumour grade, neuroendocrine markers and overall survival.
Results: Median age was 47.5 years (interquartile range: 43–61.5); right breast involvement predominated (75%). Histologic subtypes included small-cell NEC (n = 7), NET-G2 (n = 3) and large-cell NEC (n = 2). All tumours expressed ≥1 neuroendocrine marker, with INSM1 and synaptophysin most consistently positive. Hormone receptor expression was heterogeneous, while all tumours were HER2-negative. Axillary lymph node involvement occurred in 83% of patients, and distant metastases occurred in 33%, with clinical staging (American Joint Committee on Cancer Tumor,Nodes,Metastasis TNM) ranging from cT1cN0M0 to cT4bN2M1. Treatment included neoadjuvant chemotherapy (42%) and surgery (58%), followed by adjuvant systemic therapy or radiotherapy as indicated. At a median follow-up of 24 months, 33% of patients were alive with disease, 25% were alive without disease and 25% had died of progressive disease or treatment-related complications.
Conclusion: Breast NENs remain diagnostically challenging and clinically aggressive in a subset of patients, as evidenced by the death of a quarter of patients at 2-year follow-up. Accurate classification requires meticulous histopathologic evaluation supported by immunohistochemistry. Treatment mirrors standard breast cancer regimens, but outcomes remain variable, underscoring the need for collaborative research and standardised management algorithms.
