Estimating disparities in breast cancer screening programs towards mortality, case fatality, and DALYs across BRICS-plus.

BACKGROUND: Numerous studies over the past four decades have revealed that breast cancer screening (BCS) significantly reduces breast cancer (BC) mortality. However, in BRICS-plus countries, the association between BCS and BC case fatality and disability are unknown. This study examines the association of different BCS approaches with age-standardized mortality, case-fatality, and disability-adjusted life years (DALYs) rates, as well as with other biological and sociodemographic risk variables, across BRICS-plus from a national and economic perspective. METHODS: In this ecological study applying mixed-effect multilevel regression models, a country-specific dataset was analyzed by combining data from the Global Burden of Disease study 2019 on female age-standardized BC mortality, incidence, and DALYs rates with information on national/regional BCS availability (against no such program or only a pilot program) and BCS type (only self-breast examination (SBE) and/or clinical breast examination (CBE) [SBE/CBE] versus SBE/CBE with mammographic screening availability [MM and/or SBE/CBE] versus SBE/CBE/mammographic with digital mammography and/or ultrasound (US) [DMM/US and/or previous tests] in BRICS-plus countries. RESULTS: Compared to self/clinical breast examinations (SBE/CBE) across BRICS-plus, more complex BCS program availability was the most significant predictor of decreased mortality [MM and/or SBE/CBE: - 2.64, p < 0.001; DMM/US and/or previous tests: - 1.40, p < 0.001]. In the BRICS-plus, CVD presence, high BMI, second-hand smoke, and active smoking all contributed to an increase in BC mortality and DALY rate. High-income and middle-income regions in BRICS-plus had significantly lower age-standardized BC mortality, case-fatality, and DALYs rates than low-income regions when nationwide BC screening programs were implemented. CONCLUSIONS: The availability of mammography (digital or traditional) and BCS is associated with breast cancer burden in BRICS-plus countries, with regional variations. In light of high-quality evidence from previous causal studies, these findings further support the preventive role of mammography screening for BCS at the national level. Intervening on BCS related risk factors may further reduce the disease burden associated with BC.

Epidemiological and sociodemographic transitions of female breast cancer incidence, death, case fatality and DALYs in 21 world regions and globally, from 1990 to 2017: An Age-Period-Cohort Analysis.

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 (r2017 = -0.93; r1990 = -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.

Evaluation of lifestyle risk factor differences in global patterns of breast cancer mortality and DALYs during 1990-2017 using hierarchical age-period-cohort analysis.

BACKGROUND: Statistical evidence on breast cancer (BC) burden related to health and lifestyle risk factors are valuable for health policy-making. This study aimed to compare the trends in BC mortality and disability adjusted life years (DALYs) attributable to various health and life style risk factors among different world's regions according to sociodemographic index (SDI). METHODS: We extracted the age-standardized and age-specific rate of mortality and DALYs of women BC during 1990-2017 using the comparative risk assessment framework of the 2017 global burden of disease (GBD) study. We performed hierarchical age-period-cohort analysis to estimate age- and time-related trends, and effect of interactions between different risk factors on BC risk. RESULTS: During 1990-2017, the age-standardized rate of mortality and DALYs of women BC was increasing in less developed and under developing regions. The risk factor alcohol use [RR 51.3(95%CI 17.6-149.7)] and smoking [5.9(2.0-17.3)] were significantly highly contributor to increased mortality risk in high SDI region. Whereas in the low-SDI region, the greater mortality risk was observed in alcohol use [6.9(2.4-17)] and high FPG [2.7(1.5-3.1)]-related deaths. The adjusting for individual age, period, and risk factor effects, the significant interaction effect between metabolic risk factors and older ages were observed in all SDI regions and globally as well. However, an increasing cohort effect of alcohol, high fasting plasma glucose (FPG) and smoking-related death, and DALYs was observed during 1960 to 1985 cohorts among low-SDI regions. CONCLUSIONS: The age-standardized rates of mortality and DALYs due to BC has been increasing in low-SDI region. Alcohol consumption, high body mass index (BMI), high FPG, and smoking are potential BC risk factors particularly in older ages that leading to adverse disease outcomes. Therefore, rapid aging and prevalence of these prospective risk factors may strengthen the increasing mortality and DALYs of BC in low-SDI region. Hence, preventive measure along with strict action against concerned BC risk factors should be taken to reduce the disease burden specifically among lower-SDI regions.

A Hierarchical Age-Period-Cohort Analysis of Breast Cancer Mortality and Disability Adjusted Life Years (1990-2015) Attributable to Modified Risk Factors among Chinese Women.

Limited studies quantified the age, period, and cohort effects attributable to different risk factors on mortality rates (MRs) and disability-adjusted life years (DALYs) due to breast cancer among Chinese women. We used data from the Global Burden of Disease Study (GBD) in 2017. Mixed-effect and hierarchical age-period-cohort (HAPC) models were used to assess explicit and implicit fluctuations in MRs and DALYs attributable to different breast cancer associated risk factors. As the only risk factor, high body mass index (HBMI) showed continuously increasing trends in MRs and DALYs across ages, periods, and cohorts. Age, recent periods (2010-2015), and risk factor HBMI showed significant positive effect on MRs and DALYs (p < 0.05). Moreover, we reported significant interaction effects of older age and period in recent years in addition to the interplay of older age and risk factor HBMI on MRs and DALYs. Increased age and obesity contribute to substantially raised breast cancer MRs and DALYs in China and around the globe. These discoveries shed light on protective health policies and provision of healthy lifestyle for improving the subsequent breast cancer morbidity and mortality for China, as well as other related Asian regions that are presently facing the same public health challenges.

Correlation of MLH1 polymorphisms, survival statistics, in silico assessment and gene downregulation with clinical outcomes among breast cancer cases.

This study aimed to investigate the role of MLH1 polymorphisms, respective protein structure prediction, survival analysis, related clinicopathological details and MLH1 expression in breast cancer (BC). Genotyping of selected SNPs in BC patients (493) and age matched controls (387) were performed by Tetra-ARMS PCR. Gene expression among breast tumors (127) and adjacent control tissues were analysed using reverse transcriptase PCR (RT-PCR) and immunohistochemistry. Statistical analysis was performed by SPSS and MedCalc. Conditional logistic regression analysis was applied to compute the odds ratio and confidence interval. Phyre2 and I-TASSER were used to generate MLH1 protein structures and verified by a variety of computational tools. Genotyping illustrated that MLH1 polymorphisms (rs63749795 and rs63749820) were significantly associated (P ≤ 0.05) with risk of developing BC. Down regulation of MLH1 gene expression/loss of the MLH1 protein (OR 12; CI 2.8-53.1) was observed in BC cases, illustrating its potential role in disease development. Moreover, loss of the MLH1 protein was found to be associated with higher grade cancer (P = 0.02) and lymph node positivity (P = 0.03), highlighting its essential role, as a component of the mismatch repair (MMR) machinery. Bioinformatics analysis confirmed that nonsense mutations produce a truncated MLH1 protein, causing a reduction in MMR efficiency. No association between MLH1 polymorphisms and overall and progression free survival statistics was observed among BC cases, possibly due to short follow-up study. Results at DNA, RNA and protein levels, along with in silico analysis, highlights the potential role of MLH1 in DNA repair mechanisms, within BC. Therefore, it was concluded that MLH1 may contribute towards BC development and progression.