Low baseline vitamin D levels increase the risk of bone metastases among females with breast cancer - Hospital based cohort study.

BACKGROUND: Serum vitamin D (Vit-D) has been linked to the development of breast cancer (BC); however, their effect on pathological features and outcomes is undetermined. The purpose of this study was to examine the prognostic significance of baseline Vit-D levels and their effect on clinical outcomes. METHODS: We evaluated baseline serum Vit-D levels and baseline clinic-pathological features of female patients with non-metastatic BC between October 2018 and December 2019. A low Vit-D level was described as less than 30 nanogram per liter (ng/l). Patients were observed for a median of 24 months. To evaluate relationships between qualitative variables, the chi-square test was used. The Kaplan-Meier technique was used for survival analysis, and the log-rank test was used to compare the two survival curves. Correlation analysis was also used to examine the link between Vit-D levels and clinical outcomes. RESULTS: The eligibility criteria were fulfilled by 221 patients. The median age of onset was (50.7). The median Vit-D level was (23.1 ng/l) with a range of (4-46 ng/l). Approximately half of the patients (56.5%) had Vit-D levels < 30 ng/l, with HER2 positive and triple negative (TNBC) patients having a greater proportion of low Vit-D levels (p = <0.001). Patients with low baseline Vit-D levels had a larger tumor size, more positive lymph nodes, and were diagnosed at a later stage. Following follow-up, Vit-D deficiency was associated with a significantly increased risk of bone metastases (HR 3.37, 95% CI 1.32-8.59, p = 0.006), and Vit-D levels were significantly correlated with disease-free survival (DFS) and overall survival (OS) (r = 0.850, r = 0.573, p < 0.00, p < 0.001, respectively). CONCLUSIONS: Low serum Vit-D is associated with advanced stage and adverse characteristics. It is more prevalent in HER-2 positive and TNBC patients; it increases the chance of bone metastases, and has a significant correlation with DFS and OS.

Eye metastasis in breast cancer: case report and review of literature.

The paradigm of breast cancer management has been revolutionised, resulting in prolonged survival that echoes an increasing incidence of metastasis in uncommon sites. With orbital metastases - despite being rare - the incidence scales up to 13% of breast cancer cases with no specific management guidelines. We report a case of a 31-year-old luminal B breast cancer patient who initially presented with T2N2M0 disease and received six cycles of adjuvant chemotherapy (5-Fluorouracil (5-FU) 600 mg/m2 IV, Doxorubicin 60 mg/m2 IV, Cyclophosphamide 600 mg/m2 IV), followed by radiotherapy (RTH) and adjuvant Tamoxifen. Two years later, the patient experienced successive bone metastasis, so she received several lines of endocrine therapy as Fulvestrant and aromatase inhibitors in combination with luteinizing hormone-releasing hormone (LHRH) analogues. Later on, she presented with right eye ptosis and magnetic resonance imaging (MRI) showed a soft tissue mass in the superior and lateral rectus muscles. The patient received six cycles of chemotherapy with no improvement. Further disease progression occurred 3 months later, so the patient received palliative RTH resulting in no response. One month later, the patient was deceased, secondary to progressive disease. With the rising incidence of ocular metastasis due to breast cancer, oncologists should be aware of symptoms and use the proper diagnostic modalities. Here we provide a literature review on similar cases and discuss possible treatment modalities for those patients. The main concern is to evaluate the need for chemotherapy in such cases in the presence of highly effective endocrinal treatment.

PAF-R on activated T cells: Role in the IL-23/Th17 pathway and relevance to multiple sclerosis.

IL-23 is a potent stimulus for Th17 cells. These cells have a distinct developmental pathway from Th1 cells induced by IL-12 and are implicated in autoimmune and inflammatory disorders including multiple sclerosis (MS). TGF-ß, IL-6, and IL-1, the transcriptional regulator RORγt (RORC) and IL-23 are implicated in Th17 development and maintenance. In human polyclonally activated T cells, IL-23 enhances IL-17 production. The aims of our study were: 1). To validate microarray results showing preferential expression of platelet activating factor receptor (PAF-R) on IL-23 stimulated T cells. 2). To determine whether PAF-R on activated T cells is functional, whether it is co-regulated with Th17-associated molecules, and whether it is implicated in Th17 function. 3). To determine PAF-R expression in MS. We show that PAF-R is expressed on activated T cells, and is inducible by IL-23 and IL-17, which in turn are induced by PAF binding to PAF-R. PAF-R is co-expressed with IL-17 and regulated similarly with Th17 markers IL-17A, IL-17F, IL-22 and RORC. PAF-R is upregulated on PBMC and T cells of MS patients, and levels correlate with IL-17 and with MS disability scores. Our results show that PAF-R on T cells is associated with the Th17 phenotype and function. Clinical Implications Targeting PAF-R may interfere with Th17 function and offer therapeutic intervention in Th17-associated conditions, including MS.