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Background: Female breast cancer (BC) remains the most common cause of total cancer deaths around the world. Several studies have investigated BC biomarkers, but vital circulating biomarkers for early diagnosis of malignancy are still scarce. Thus, finding sensitive, selective and accurate biomarkers is required to get better BC outcome and to prolong patients’ survival. Therefore, this review investigated the feasibility of using circulating trace elements (TEs) as the new promising biological biomarkers for BC diagnosis and prevention. Methods: We systematically searched EMBASE, Medline, Google Scholar, PubMed, SciELO, Scopus databases or Web of Science for orginal studies presenting the significant changes in the concentrations of circulating TEs in terms of serum, plasma or blood from female breast cancer patients. Results: The search yielded 2697 articles, of which 39 were considered for this review. The study showed that four essential TEs (Se, Cu, Zn and Mn) significantly decreased when only one essential trace elemnt (Fe) increased consistently, while five toxics circulating TEs (Cd, Cr, Pb, Co, Mo) increased significantly with a significant difference compared to healthy groups. The essential TEs, Se and Cu were reported to decrease the most in fifteen and twenty-one studies, respectively. However, regarding the toxic circulating TEs, Cd and Pb were found to increase most significantly in seven studies. Among the essential TEs, Se and Zn were reported to have the most potential, with Cd and Pb having the most potential for use as new promising biomarkers to diagnose or prevent BC. Conclusion: The findings provide an insight into the TEs circulating biomarkers for early BC diagnosis and prevention. Due to its high heterogeneity, meta-analysis was not assessed; hence, futher investigation may be required on their clinical outcomes in BC with high sensitivity and specificity for accurate therapeutic response.

The renin angiotensin system (RAS) is composed of several enzymes and substrates on which angiotensin converting enzyme (ACE) 1 and renin act to produce angiotensin II. ACE1 and its substrates control blood pressure, affect cardiovascular and renal function, hematopoiesis, reproduction, and immunity. The increased expression of ACE1 has been observed in human monocytes during congestive heart failure and abdominal aortic aneurysm. Moreover, T lymphocytes from hypertensive patients presented increased expression of ACE1 gene after in vitro stimulation with Angiotensin-II (AngII) with the highest ACE1 expression observed in hypertensive patients with low-grade inflammation. Our group and others have shown that aging is associated with comorbidities, chronic inflammation and immunosenescence, but there is a lack of data about ACE1 expression on immune cells during the aging process. Therefore, our aim was to evaluate the levels of ACE1 expression in non-lymphoid as compared to lymphoid cells in association with the immunosenescence profile in adults older than 60 years. Cryopreserved peripheral blood mononuclear cells obtained from blood samples were used. Cells were stained with monoclonal antibodies and evaluated by flow cytometry. We found that ACE1 was expressed in 56.9% of non-lymphocytes and in more than 90% of lymphocytes (all phenotypes). All donors exhibited characteristics of immunosenescence, as evaluated by low frequencies of Naive CD4+and CD8+T cells, high frequencies of EMRA CD8+T cells, and double-negative memory B cells. These findings in addition to the increased C-reactive protein levels are intriguing questions for the study of ACE1, inflammaging, immunosenescence and perspectives for drug development or repurposing.