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Objective: To investigate whether preoperative localization of sentinel lymph node (SLN) by contrast-enhanced ultrasound (CEUS) can further improve the accuracy of sentinel lymph node biopsy (SLNB). Method: Collect published literatures or conference reports by searching electronic databases. The Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) evaluation method is used to evaluate the quality of the screened literatures. The pooled risk ratio of cancer metastasis of SLN identified by CEUS (CE-SLN) compared with SLN not identified by CEUS (nonCE-SLN) is calculated, and the pooled diagnostic accuracy of CE-SLN for pathological status of all SLNs is also evaluated. Result: Through search and screening, a total of 16 studies were included, of which five and seven studies, respectively, entered the meta-analysis of metastatic risk ratio and diagnostic accuracy. The localization rate of preoperative CEUS for sentinel lymph nodes was 70 to 100%. The meta-analysis shows that the risk of metastasis of SLN identified by CEUS is significantly higher than that not identified by CEUS, 26.0% vs 4.6%, and risk ratio (RR) is 6.08 (95% CI 4.17-8.85). In early-stage breast cancer, the pathological status of CE-SLN is a good representative of all SLNs, with a pooled sensitivity of 98% (95% CI 0.94-1.00), pooled specificity of 100% (95% CI 0.99-1.00), diagnostic odds ratio (DOR) of 2153.18 (95% CI 476.53-9729.06), and area under the subject receiver operating characteristic (SROC) curve of 0.9968. Conclusion: In early-stage breast cancer, preoperative localization of SLN by CEUS is expected to further improve the accuracy of sentinel lymph node biopsy (SLNB).

BackgroundPrevious studies suggested that the molecular subtypes were strongly associated with sentinel lymph node (SLN) status. The purpose of this study was to determine whether molecular subtype classification was associated with non-sentinel lymph nodes (NSLN) metastasis in patients with a positive SLN.Methodology and Principal FindingsBetween January 2001 and March 2011, a total of 130 patients with a positive SLN were recruited. All these patients underwent a complete axillary lymph node dissection. The univariate and multivariate analyses of NSLN metastasis were performed. In univariate and multivariate analyses, large tumor size, macrometastasis and high tumor grade were all significant risk factors of NSLN metastasis in patients with a positive SLN. In univariate analysis, luminal B subgroup showed higher rate of NSLN metastasis than other subgroup (P = 0.027). When other variables were adjusted in multivariate analysis, the molecular subtype classification was a determinant of NSLN metastasis. Relative to triple negative subgroup, both luminal A (P = 0.047) and luminal B (P = 0.010) subgroups showed a higher risk of NSLN metastasis. Otherwise, HER2 over-expression subgroup did not have a higher risk than triple negative subgroup (P = 0.183). The area under the curve (AUC) value was 0.8095 for the Cambridge model. When molecular subtype classification was added to the Cambridge model, the AUC value was 0.8475.ConclusionsExcept for other factors, molecular subtype classification was a determinant of NSLN metastasis in patients with a positive SLN. The predictive accuracy of mathematical models including molecular subtype should be determined in the future.

Genetic variants may influence miRNA-mRNA interaction through modulate binding affinity, creating or destroying miRNA-binding sites. Twenty-four single nucleotide polymorphisms (SNPs) that were predicted to affect the binding affinity of breast cancer-related miRNAs to 3'-untranslated regions (UTR) of known genes were genotyped in 878 breast cancer cases and 900 controls in Chinese women. Three promising SNPs (rs10494836, rs10857748 and rs7963551) were further validated in additional 914 breast cancer cases and 967 controls. The variant allele (C) of rs7963551 at 3'-UTR of RAD52 showed a consistently reduced breast cancer risk in two stages with a combined odds ratio (OR) of 0.84 [95% confidence interval (CI) = 0.75-0.95], which was more prominent among women with early age at first live birth (OR = 0.71, 95% CI = 0.58-0.87). A significant interaction was observed between rs7963551 and age at first live birth on breast cancer risk (P for interaction = 0.04). Luciferase activity assay showed a higher expression level for rs7963551 C allele as compared with A allele (P = 5.19 × 10(-3) for MCF-7 cell lines), which might be due to a reduced inhibition from a weakened binding capacity of miRNA to 3'-UTR of RAD52 harboring C allele. These findings indicate that rs7963551 located at hsa-let-7 binding site may alter expression of RAD52 through modulating miRNA-mRNA interaction and contribute to the development of breast cancer in Chinese women.