Metastatic primary breast neuroendocrine neoplasms: A case series

Abstract

Background: Breast neuroendocrine neoplasms (NENs) represent a rare subtype of breast cancer and have not been well studied or characterised, particularly in the metastatic setting. Aim(s): The aim of this case series is to discuss the clinical and pathologic features, treatment and prognosis of patients with metastatic NENs of breast origin and review the current literature. Case Presentation: We present a series of six female patients with primary neuroendocrine breast cancer as defined by the 2012 WHO classification with metastatic disease diagnosed over a period of 8 years (2011-2019) from a single centre. Median age at diagnosis was 49 years (range 39 to 63). Four of six patients presented with widespread metastatic disease at diagnosis. Diagnosis was made with wide local excision or mastectomy in three patients, breast core biopsy in one and liver biopsy in two. Five of six tissue samples expressed synaptophysin and chromogranin andwere also oestrogen and progesterone receptor positive; median ki67 index was 40% (range 20-90%). All six patients had demonstrated avidity on FDG PET imaging and the five who underwent DOTATATE PET all had significant avidity. Treatment modalities and sequencing varied but all patients received chemotherapy during their disease course, usually carboplatin and etoposide, and four of six patients received anti-oestrogen treatment. Four patients received three or more lines of treatment. Medianoverall survival was not reached and median progression-free survival with first-line therapy was 6.8 months (range 1.8-36). Conclusion(s): Primary breast NENs are uncommon and more research is needed, particularly in the metastatic setting where patients are younger and tend to have high-grade disease. This series shows the use of multiple modalities in treating this disease, with different sequencing in different patients. Larger series and further molecular characterisation are required to aid clinicians in managing this condition and to guide optimal treatment sequencing.