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Introduction: Breast cancer (BC) is the most widely studied disease due to its higher prevalence, heterogeneity and mortality., Objectives: This study aimed to compare female BC trends among 21 world regions and globally over 28 year of data and to assess the association between sociodemographic transitions and female BC risks., Methods: We used Global burden of disease study data and measure the female BC burden according to 21 world regions and sociodemographic indices (SDI). Age-period-cohort (APC) analysis was used to estimate time and cohort trend of BC in different SDI regions., Results: By world regions, age-standardised rate of female BC incidence were high in high-income-North America (ASR, 92.9; (95 %UI, 89.2, 96.6)), Western Europe (84.7; (73.4, 97.2)) and Australia (86; (81.7, 90.2)) in 2017. Whereas this rate was significantly increased by 89.5% between 1990 and 2017 in East Asia. We observed negative association between SDI and death, and DALYs in 25th and below percentiles of death and DALYs for the worldwide regions. Further, there was observed a strong negative correlation between SDI and case fatality percent (r 2017  = -0.93; r 1990  = -0.92) in both 2017 and 1990 worldwide and highest case fatality percentage was observed in Central Sub-Saharan Africa. Overall, the risk of case-fatality rate tends to decrease most noticeably in high middle SDI countries, and the reduction of the risk of case-fatality rate in the recent cohort was the lowest in the low SDI countries., Conclusions: Remarkable variations exist among various regions in BC burden. There is a need to reduce the health burden from BC in less developed and under developing countries, because under-developed countries are facing higher degree of health-related burden. Public health managers should execute more classified and cost-effective screening and treatment interferences to lessen the deaths caused by BC, predominantly among middle and low SDI countries having inadequate healthcare supplies., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Authors. Published by Elsevier B.V. on behalf of Cairo University.)

Introduction: Hydrogen sulphide (H 2 S) has been established as a key member of the gasotransmitters family that recently showed a pivotal role in various pathological conditions including cancer., Objectives: This study investigated the role of H 2 S in breast cancer (BC) pathogenesis, on BC immune recognition capacity and the consequence of targeting H 2 S using non-coding RNAs., Methods: Eighty BC patients have been recruited for the study. BC cell lines were cultured and transfected using validated oligonucleotide delivery system. Gene and protein expression analysis was performed using qRT-PCR, western blot and flow-cytometry. In-vitro analysis for BC hallmarks was performed using MTT, BrdU, Modified Boyden chamber, migration and colony forming assays. H 2 S and nitric oxide (NO) levels were measured spectrophotometrically. Primary natural killer cells (NK cells) and T cell isolation and chimeric antigen receptor transduction (CAR T cells) were performed using appropriate kits. NK and T cells cytotoxicity was measured. Finally, computational target prediction analysis and binding confirmation analyses were performed using different software and dual luciferase assay kit, respectively., Results: The H 2 S synthesizing enzymes, cystathionine β-synthase (CBS) and cystathionine γ-lyase (CSE), exhibited elevated levels in the clinical samples that correlated with tumor proliferation index. Knock-down of CBS and CSE in the HER2+ BC and triple negative BC (TNBC) cells resulted in significant attenuation of BC malignancy. In addition to increased susceptibility of HER2+ BC and TNBC to the cytotoxic activity of HER2 targeting CAR T cells and NK cells, respectively. Transcriptomic and phosphoprotein analysis revealed that H 2 S signaling is mediated through Akt in MCF7, STAT3 in MDA-MB-231 and miR-155/ NOS2/NO signaling in both cell lines. Lastly, miR-4317 was found to function as an upstream regulator of CBS and CSE synergistically abrogates the malignancy of BC cells., Conclusion: These findings demonstrate the potential role of H 2 S signaling in BC pathogenesis and the potential of its targeting for disease mitigation., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2020 The Authors. Published by Elsevier B.V. on behalf of Cairo University.)