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High neutrophil to lymphocyte ratio (NLR) and monocyte to lymphocyte ratio (MLR) are respectively associated with systemic inflammation and immune suppression and have been associated with a poor outcome. Plasmatic exosomes are extracellular vesicles involved in the intercellular communication system that can exert an immunosuppressive function. Aim of this study was to investigate the interplay between the immune system and circulating exosomes in metastatic breast cancer (MBC). A threshold capable to classify patients according to MLR, NLR and PLR, was computed through a receiving operator curve analysis after propensity score matching with a series of female blood donors. Exosomes were isolated from plasma by ExoQuick solution and characterized by flow-cytometry. NLR, MLR, PLR and exosomal subpopulations potentially involved in the pre-metastatic niche were significantly different in MBC patients with respect to controls. MLR was significantly associated with number of sites at the onset of metastatic disease, while high levels of MLR and NLR were found to be associated with poor prognosis. Furthermore, exosomal subpopulations varied according to NLR, MLR, PLR and both were associated with different breast cancer subtypes and sites of distant involvement. This study highlights the nuanced role of immunity in MBC spread, progression and outcome. Moreover, they suggest potential interaction mechanisms between immunity, MBC and the metastatic niche. [ABSTRACT FROM AUTHOR]

Background: Limited data are available on the prognostic performance of Adjuvant! Online (AOL) and Nottingham Prognostic Index (NPI) in young breast cancer patients.Methods: This multicentre hospital-based retrospective cohort study included young (⩽40 years) and older (55-60 years) breast cancer patients treated from January 2000 to December 2004 at four large Belgian and Italian institutions. Predicted 10-year overall survival (OS) and disease-free survival (DFS) using AOL and 10-year OS using NPI were calculated for every patient. Tools ability to predict outcomes (i.e., calibration) and their discriminatory accuracy was assessed.Results: The study included 1283 patients, 376 young and 907 older women. Adjuvant! Online accurately predicted 10-year OS (absolute difference: 0.7%; P=0.37) in young cohort, but overestimated 10-year DFS by 7.7% (P=0.003). In older cohort, AOL significantly underestimated both 10-year OS and DFS by 7.2% (P<0.001) and 3.2% (P=0.04), respectively. Nottingham Prognostic Index significantly underestimated 10-year OS in both young (8.5%; P<0.001) and older (4.0%; P<0.001) cohorts. Adjuvant! Online and NPI had comparable discriminatory accuracy.Conclusions: In young breast cancer patients, AOL is a reliable tool in predicting OS at 10 years but not DFS, whereas the performance of NPI is sub-optimal. [ABSTRACT FROM AUTHOR]

Although antiangiogenic treatments have produced milestone advances in the treatment of several diseases, and have significantly extended the median survival of cancer patients, these agents share some weaknesses, including a limited impact on the overall cure rate, a fleeting effect because of redundant pathways or early appearance of resistance mechanisms, and the lack of predictive factors for treatment selection. Recent data suggest that antibodies targeting the vascular endothelial growth factor axis exert their activity through the inhibition of vascular endothelial growth factor receptor-2 phosphorylation, which has a pivotal role in the neoangiogenic process. Ramucirumab, a fully humanized monoclonal antibody specifically directed against the extracellular domain of the receptor, administered intravenously every 2 or 3 weeks, is emerging as a novel antiangiogenic opportunity. Starting with preclinical data and early clinical results, this concise review focuses on the development of the novel compound across multiple cancers (including gastrointestinal malignancies, breast cancer, lung carcinoma, and genitourinary tumors), and presents available data from randomized phase II and phase III trials. REGARD was the first phase III study to report on the efficacy of single-agent ramucirumab in patients with advanced cancer. Many other ongoing phase III trials are testing the efficacy of this interesting antiangiogenic compound as a single agent or in combination with chemotherapy in different cancer types. [ABSTRACT FROM AUTHOR]