Characteristics of male triple negative breast cancer: A population-based study.

Male triple negative breast cancer (TNBC), which lacks expression of the estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2), is a very rare entity, comprising only a very small percentage of all male breast cancer cases. Management strategies are typically based off research conducted in female TNBC patients; however, there is still much that remains unknown in the male cohort, such as risk factors for developing these malignancies, the optimal treatment approach, and both short-term and long-term outcome data. In this retrospective cohort study, we aimed to address these concerns by assessing both the characteristics of male patients who develop TNBC as well as their outcomes. We harnessed data from the National Cancer Institute Surveillance, Epidemiology, and End Results (SEER) Program and identified 66 male patients diagnosed with TNBC between 2010 and 2016. Patients were stratified by several variables including age, insurance status, time period of diagnosis, histology, nodal status, tumor grade, tumor stage at diagnosis, and treatment strategy employed for the assessment of overall survival (OS) differences. Our analysis demonstrated that stage remains the most important prognostic factor for OS, with higher stage corresponding to worse OS. A significant OS benefit was also identified in men undergoing a total mastectomy, compared to partial mastectomy or no surgery at all. We also identified that male patients are more likely to present with more advanced disease stages compared to their female counterparts and, therefore, have worse outcomes on average. This may be due to various factors, including the rarity of male TNBC cases and less clear screening guidelines for male breast cancer in general. Trends toward poorer OS with higher tumor grade, higher tumor T stage, advanced age, earlier time period of diagnosis, and ductal histology were also identified, but did not achieve statistical significance. The remaining variables did not appear to influence outcomes in a meaningful manner. In summary, our study suggests, similar to population studies of women with TNBC, that tumor stage is a major prognostic factor of OS in men with TNBC. The data also suggest that the surgical treatment strategy employed is also likely of significance, with improved OS being seen with total mastectomies over partial mastectomies. Other variables such as tumor grade and T stage also likely play a role, but did not achieve statistical significance owing to the small population size. Owing to the rarity of cases, further studies of male TNBC are needed to better understand this rare entity and guide future management strategies.

Mechanisms by which the orexigen NPY regulates anorexigenic α-MSH and TRH.

Protein posttranslational processing is a cellular mechanism fundamental to the generation of bioactive peptides, including the anorectic α-melanocyte-stimulating hormone (α-MSH) and thyrotropin-releasing hormone (TRH) peptides produced in the hypothalamic arcuate (ARC) and paraventricular (PVN) nuclei, respectively. Neuropeptide Y (NPY) promotes positive energy balance in part by suppressing α-MSH and TRH. The mechanism by which NPY regulates α-MSH output, however, is not well understood. Our results reveal that NPY inhibited the posttranslational processing of α-MSH's inactive precursor proopiomelanocortin (POMC) by decreasing the prohormone convertase-2 (PC2). We also found that early growth response protein-1 (Egr-1) and NPY-Y1 receptors mediated the NPY-induced decrease in PC2. NPY given intra-PVN also decreased PC2 in PVN samples, suggesting a reduction in PC2-mediated pro-TRH processing. In addition, NPY attenuated the α-MSH-induced increase in TRH production by two mechanisms. First, NPY decreased α-MSH-induced CREB phosphorylation, which normally enhances TRH transcription. Second, NPY decreased the amount of α-MSH in the PVN. Collectively, these results underscore the significance of the interaction between NPY and α-MSH in the central regulation of energy balance and indicate that posttranslational processing is a mechanism that plays a specific role in this interaction.