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Background Female breast cancer (FBC) is a malignancy involving multiple risk factors and has imposed heavy disease burden on women. We aim to analyze the secular trends of mortality rate of FBC according to its major risk factors. Methods Death data of FBC at the global, regional, and national levels were retrieved from the online database of Global Burden of Disease study 2017. Deaths of FBC attributable to alcohol use, high body-mass index (BMI), high fasting plasma glucose (FPG), low physical activity, and tobacco were collected. Estimated average percentage change (EAPC) was used to quantify the temporal trends of age-standardized mortality rate (ASMR) of FBC in 1990–2017. Results Worldwide, the number of deaths from FBC increased from 344.9 thousand in 1990 to 600.7 thousand in 2017. The ASMR of FBC decreased by 0.59% (95% CI, 0.52, 0.66%) per year during the study period. This decrease was largely driven by the reduction in alcohol use- and tobacco-related FBC, of which the ASMR was decreased by 1.73 and 1.77% per year, respectively. In contrast, the ASMR of FBC attributable to high BMI and high FPG was increased by 1.26% (95% CI, 1.22, 1.30%) and 0.26% (95% CI, 0.23, 0.30%) per year between 1990 and 2017, respectively. Conclusions The mortality rate of FBC experienced a reduction over the last three decades, which was partly owing to the effective control for alcohol and tobacco use. However, more potent and tailored prevention strategies for obesity and diabetes are urgently warranted.

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Background. The purpose of this study was to investigate the regulatory mechanisms of ceRNAs in breast cancer (BC) and construct a new five-mRNA prognostic signature. Methods. The ceRNA network was constructed by different RNAs screened by the edgeR package. The BC prognostic signature was built based on the Cox regression analysis. The log-rank method was used to analyse the survival rate of BC patients with different risk scores. The expression of the 5 genes was verified by the GSE81540 dataset and CPTAC database. Results. A total of 41 BC-adjacent tissues and 473 BC tissues were included in this study. A total of 2,966 differentially expressed lncRNAs, 5,370 differentially expressed mRNAs, and 359 differentially expressed miRNAs were screened. The ceRNA network was constructed using 13 lncRNAs, 267 mRNAs, and 35 miRNAs. Kaplan-Meier (K-M) methods showed that two lncRNAs (AC037487.1 and MIR22HG) are related to prognosis. Five mRNAs (VPS28, COL17A1, HSF1, PUF60, and SMOC1) in the ceRNA network were used to establish a prognostic signature. Survival analysis showed that the prognosis of patients in the low-risk group was significantly better than that in the high-risk group (p=0.0022). ROC analysis showed that this signature has a good diagnostic ability (AUC=0.77). Compared with clinical features, this signature was also an independent prognostic factor (HR: 1.206, 95% CI 1.108−1.311; p<0.001). External verification results showed that the expression of the 5 mRNAs differed between the normal and tumour groups at the chip and protein levels (p<0.001). Conclusions. These ceRNAs may play a key role in the development of BC, and the new 5-mRNA prognostic signature can improve the prediction of survival for BC patients.

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