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Objectives: To evaluate the performance of readout-segmented echo-planar imaging DWI (rs-EPI DWI) in detecting and characterizing breast cancers in a large Chinese cohort with comparison to dynamic contrast-enhanced MRI (DCE-MRI). Methods: The institutional review board approved this retrospective study with waived written informed consent. A total of 520 women (mean age, 43.1- ± 10.5-years) were included from July 2013 to October 2019. First, the ability of rs-EPI DWI in detecting breast lesions identified by DCE-MRI was evaluated. The lesion conspicuity of rs-EPI-DWI and DCE-MRI was compared using the Wilcoxon signed rank test. With pathology as a reference, the performance of rs-EPI DWI and DCE-MRI in distinguishing breast cancers was evaluated and compared using the Chi-square test. Results: Of 520 women, 327/520 (62.9%) patients had 423 lesions confirmed by pathology with 203 benign and 220 malignant lesions. The rs-EPI DWI can detect 90.8% (659/726) (reader 1) and 90.6% (663/732) (reader 2) of lesions identified by DCE-MRI. The lesion visibility was superior for DCE-MRI than rs-EPI-DWI (all p < 0.05). With pathology as a reference, the sensitivities and specificities of rs-EPI DWI in diagnosing breast cancers were 95.9% (211/220) and 85.7% (174/203) for reader 1 and 97.7% (215/220) and 86.2% (175/203) for reader 2. No significant differences were found for the performance of DCE-MRI and rs-EPI DWI in discriminating breast cancers (all p > 0.05). Conclusions: Although with an inferior lesion visibility, rs-EPI DWI can detect about 90% of breast lesions identified by DCE-MRI and has comparable diagnostic capacity to that of DCE-MRI in identifying breast cancer. [ABSTRACT FROM AUTHOR]

Toll-like receptor 3 (TLR3) is a viral sensor that induces apoptosis in response to double-stranded RNA (dsRNA). Common genetic changes in the TLR3 gene may influence breast cancer susceptibility and development. However, all of the polymorphisms in the previous study were only markers of the TLR3 gene, not causative polymorphisms. In this study, we performed a case-control study focusing on the relationship between rs5743305 (−926T>A), a single nucleotide polymorphism (SNP) in the promoter region of TLR3, and breast cancer. We found that the genetic variant rs5743305 increased the risk of breast cancer under the dominant and codominant models (dominant model: AT+AA vs TT.: OR = 1.3023, 95%CI: 1.0778–1.5736, P =.0062; codominant model: AA vs. TT: OR = 1.3919, 95%CI: 1.0177–1.9036, P =.0384; AT vs. TT: OR = 1.2799, 95%CI: 1.0475–1.5639, P =.0158) but not under the recessive model (TT vs. AT+AA, OR = 1.2387, 95%CI: 0.9197–1.6682, P =.1588). The same trends were found in the age-adjusted logistic regression study and stage 2 study. Furthermore, the electrophoretic mobility shift assay (EMSA) and luciferase reporter assay showed that rs5743305 decreased the transcriptional activity of TLR3. There was consistently reduced TLR3 mRNA and protein expression in human breast cancer samples from patients with TLR3 − 926A. Therefore, TLR3 rs5743305 increases the risk of breast cancer by decreasing the transcriptional activity of TLR3. This study may provide a better understanding of the genetic architecture underlying disease susceptibility and may advance the potential for preclinical prediction in future genetic testing. [ABSTRACT FROM AUTHOR]

Toll-like receptor 3 (TLR3) is a receptor recognizing double-stranded RNA (dsRNA) from viruses as well as from lytic mammalian cells. In the present study, we performed a two-stage association study (n = 3,551) and found that the minor alleles of two SNPs (the T-allele of rs5743312 and the T-allele of rs3775296) conferred increased risks of breast cancer incidence. The adjusted odds ratios (ORs) were 2.281 (P = 7.01 × 10−5) and 2.086 (P = 8.69 × 10−5), respectively. Specifically, the susceptibility variants within TLR3 were significantly associated with larger tumor size (adjusted P-values: 0.004 for rs5743312 and 0.004 for rs3775296). Furthermore, we investigated the biological function of the TLR3 protein in breast cancer cell lines. Notably, the stable expression of TLR3 directly inhibited cell proliferation both in vitro and in vivo. We also verified that TLR3 conferred less invasive phenotypes on breast cancer cells by regulating the mRNA expression of a panel of genes. TLR3-mediated inhibition of proliferation was caused by downregulation of the EGFR/PI3K/AKT pathway. In summary, our findings strongly suggest that common genetic changes in the TLR3 gene may influence breast cancer susceptibility and development, and TLR3 plays a negative regulatory role in the initiation and progression of human breast cancer cells, at least in part by downregulating the EGFR/PI3K/AKT pathway. [ABSTRACT FROM AUTHOR]