Neuroendocrine carcinoma of the breast is considered a rare entity, and for this reason there are no data from prospective clinical trials on its optimal management. Early stage tumors are usually treated with the same strategy used for the other types of invasive breast cancer. Anthracycline-and taxane-based regimens represent the most frequently administered chemotherapy in neoadjuvant and adjuvant setting, as well as for metastatic disease, although combinations of platinum compounds and etoposide have been widely used, in particular for small-cell histology and tumors with a high proliferation index. For metastatic disease, 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. In the near future, a better knowledge of the biology of these tumors will hopefully provide new therapeutic targets for personalized treatment. In this review, we discuss the current evidence and the future perspectives on diagnosis and treatment of neuroendocrine carcinoma of the breast. The Oncologist 2016;21:28-32 Implications for Practice: Neuroendocrine carcinoma of the breast (NECB) is a distinct entity of breast cancer. Clinical features and morphology are not helpful to distinguish NECB from other subtypes of breast cancer; therefore, immunohistochemistry markers for neuroendocrine differentiation, mainly chromogranin and synaptophysin, should be routinely used to confirm the diagnosis, especially in cases of mucinous or solid papillary carcinoma in which the suspicion of NECB may be relevant. Adjuvant treatment should be offered according to the same recommendations given for the other types of invasive breast cancer. An accurate diagnosis of NECB is also important in the metastatic setting, in which a multimodality approach including specific therapies such as peptide receptor radionuclide therapy can be considered.

Immunotherapy with checkpoint inhibitors, allowing recovery of effector cells function, has demonstrated to be highly effective in many tumor types and represents a true revolution in oncology. Recently, the anti-PD1 agent pembrolizumab was granted FDA approval for the first line treatment of patients with advanced non–small cell lung cancer (NSCLC) whose tumors show PD-L1 expression in ≥ 50% of neoplastic cells and as a second line treatment for patients with NSCLC expressing PD-L1 in ≥1% of neoplastic cells, evaluated with a validated assay. For the large majority of patients such evaluation is made on small biopsies. However, small tissue samples such as core biopsies might not be representative of tumors and may show divergent results given the possible heterogeneous immunoexpression of the biomarker. We therefore sought to evaluate PD-L1 expression concordance in a cohort of 239 patients using tissue microarrays (TMA) as surrogates of biopsies stained with a validated PD-L1 immunohistochemical assay (SP263) and report the degree of discordance among tissue cores in order to understand how such heterogeneity could affect decisions regarding therapy.We observed a discordance rate of 20% and 7.9% and a Cohen's κ value of 0.53 (moderate) and 0,48 (moderate) for ≥ 1% and ≥ 50% cutoffs, respectively.Our results suggest that caution must be taken when evaluating single biopsies from patients with advanced NSCLC eligible for immunotherapy; moreover, at least 4 biopsies are necessary in order to minimize the risk of tumor misclassification.

The high sensitivity of Ga-PET/CT in NET detection is known. The high PPV of F-PET/CT in the identification of G2 forms suggests its potential role in PanNETs prognostication and risk stratification.

Purpose: The aim of this study was to evaluate the effect of combined ⁶⁸Ga and ¹⁸F-FDG PET/CT on treatment management for patients with pancreatic neuroendocrine tumor (PNET). Methods: Between January 2012 and April 2014, 49 consecutive patients with a cytologically and/or histologically proven diagnosis of PNET underwent combined ⁶⁸Ga and ¹⁸FDG PET/CT on the same day. Results: The study group consisted of 21 males and 28 females with a median age of 59 years. Disease detection was achieved in 48 out of the 49 cases with ⁶⁸Ga imaging, and in 36 of the 49 cases with ¹⁸FDG PET/CT. These results corresponded to sensitivities of 98% for ⁶⁸Ga versus 73% for ¹⁸FDG PET/CT. Patients with NET-G1/NET-G2 had a positive ⁶⁸Ga and negative ¹⁸FDG PET/CT in 13 cases, whereas both ⁶⁸Ga and ¹⁸FDG PET/CT were positive in 27 cases. Patients with NEC-G3 were positive by both ⁶⁸Ga and ¹⁸FDG PET/CT in 7 cases and positive only by ¹⁸FDG in 1 case. Another NEC-G3 patient was only positive by ⁶⁸Ga PET/CT. The median Ki67 was 7% for ⁶⁸Ga PET/CT-positive tumors and 10% for tumors with both ⁶⁸Ga and ¹⁸FDG PET/CT positivity (p = 0.130). Half of the patients with a prevalent uptake of ¹⁸FDG (n = 7) had an NEC-G3 compared with 12% of patients with a prevalent uptake of ⁶⁸Ga (p = 0.012). There were no significant differences between patients with positive ⁶⁸Ga and those with positive ¹⁸FDG with regards to treatment choice. Conclusions: The association of ¹⁸FDG slightly increases sensitivity of ⁶⁸Ga PET/CT alone in the diagnosis of PNET. A combined dual tracer PET/CT does not influence the choice of treatment strategy.