Abstract / Summary
Abstract Introduction: Primary small cell neuroendocrine carcinoma (SCNEC) of the breast comprises less than 0.1% of all breast cancers. Optimal management remains undefined due to the absence of prospective data and therapeutic strategies. Case Presentation: We present a 56-year-old woman diagnosed with poorly differentiated SCNEC of the breast Stage IIIA (cT2N1M0), triple negative. She progressed on neoadjuvant carboplatin and etoposide and developed new hepatic metastases. Liver biopsy confirmed S CNEC (ER 0%, PR 0%, HER2 IHC 0, Ki-67 99%, PD-L1 CPS 0, DLL3 IHC 90%). She was then treated with weekly paclitaxel but progressed within six weeks. Subsequently, she received tarlatamab, a DLL3-directed bispecific T-cell engager, but experienced hepatic progression after only three cycles. Genomic profiling identified high PRAME expression, and the patient was enrolled on a PRAME-directed T cell receptor (TCR)-engineered T cell therapy. Imaging showed favorable response on Day 42 post T-cell-infusion, however, day 60 scans revealed new liver lesions. She is currently enrolled in a clinical trial evaluating safety and tolerability of a DLL3 ADC, BL-M14D1 (NCT07080242, study registration date: 7/14/2025, https://www.clinicaltrials.gov). Conclusion: This case illustrates and rapidly evolving landscape of targetable biology in SCNEC of the breast. It highlights the potential relevance of DLL3 expression as a biomarker across neuroendocrine histology and the emerging role of PRAME-directed therapies. Further research is needed for advancing the management of this rare breast cancer subtype.