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Background: In recent years, breast cancer has become the most common cancer in the world, increasing women's health risks. Approximately 60% of breast cancers are categorized as human epidermal growth factor receptor 2 (HER2)-low tumors. Recently, antibody-drug conjugates have been found to have positive anticancer efficacy in patients with HER2-low breast cancer, but more studies are required to comprehend their clinical and molecular characteristics. Methods: In this study, we retrospectively analyzed the data of 165 early breast cancer patients with pT1-2N1M0 who had undergone the RecurIndex testing. To better understand HER2-low tumors, we investigated the RecurIndex genomic profiles, clinicopathologic features, and survival outcomes of breast cancers according to HER2 status. Results: First, there were significantly more hormone receptor (HR)-positive tumors, luminal-type tumors, and low Ki67 levels in the HER2-low than in the HER2-zero. Second, RI-LR (P =.0294) and RI-DR (P =.001) scores for HER2-low and HER2-zero were statistically significant. Third, within HER2-negative disease, HR-positive/HER2-low tumors showed highest ESR1, NFATC2IP, PTI1, ERBB2, and OBSL1 expressions. Fourth, results of the survival analysis showed that lower expression of HER2 was associated with improved relapse-free survival for HR-positive tumors, but not for HR-negative tumors. Conclusions: The present study highlights the unique features of HER2-low tumors in terms of their clinical characteristics as well as their gene expression profiles. HR status may influence the prognosis of patients with HER2-low expression, and patients with HR-positive/HER2-low expression may have a favorable outcome. In this study, the data of patients with early stage breast cancer who had undergone RecurIndex testing was analyzed. To better understand HER2-low tumors, genomic profiles, clinicopathologic features, and survival outcomes of breast cancers according to HER2 status were investigated. [ABSTRACT FROM AUTHOR]

Recent studies suggest that paired box 5 (PAX5) is down-regulated in multiple tumours through its promoter methylation. However, the role of PAX5 in non-small cell lung cancer (NSCLC) pathogenesis remains unclear. The aim of this study is to examine PAX5 expression, its methylation status, biological functions and related molecular mechanism in NSCLC. We found that PAX5 was widely expressed in normal adult tissues but silenced or down-regulated in 88% (7/8) of NSCLC cell lines. PAX5 expression level was significantly lower in NSCLC than that in adjacent non-cancerous tissues (P = 0.0201). PAX5 down-regulation was closely associated with its promoter hypermethylation status and PAX5 expression could be restored by demethylation treatment. Frequent PAX5 promoter methylation in primary tumours (70%) was correlated with lung tumour histological types (P = 0.006). Ectopic expression of PAX5 in silenced lung cancer cell lines (A549 and H1975) inhibited their colony formation and cell viability, arrested cell cycle at G2 phase and suppressed cell migration/invasion as well as tumorigenicity in nude mice. Restoration of PAX5 expression resulted in the down-regulation of β-catenin and up-regulation of tissue inhibitors of metalloproteinase 2, GADD45G in lung tumour cells. In summary, PAX5 was found to be an epigenetically inactivated tumour suppressor that inhibits NSCLC cell proliferation and metastasis, through down-regulating the b-catenin pathway and up-regulating GADD45G expression. [ABSTRACT FROM AUTHOR]

Multiple mechanisms have been detected to account for the acquired resistance to endocrine therapies in breast cancer. In this study we retrospectively studied the mechanism of primary endocrine resistance in estrogen receptor positive (ER + ) breast cancer patients by next-generation sequencing (NGS). Tumor specimens and matched blood samples were obtained from 24 ER + breast cancer patients. Fifteen of them displayed endocrine resistance, including recurrence and/or metastases within 24 months from the beginning of endocrine therapy, and 9 patients remained sensitive to endocrine therapy for more than 5 years. Genomic DNA of tumor tissue was extracted from formalin-fixed paraffin-embedded (FFPE) tumor tissue blocks. Genomic DNA of normal tissue was extracted from peripheral blood mononuclear cells (PBMC). Sequencing libraries for each sample were prepared, followed by target capturing for 372 genes that are frequently rearranged in cancers. Massive parallel sequencing was then performed using Illumina NextSeq 500, and samples with a mean sequencing depth of 500× were analyzed. The analysis revealed that 8 (55%) of 15 patients showed phosphatidylinositol 3-kinase CA (PIK3CA) mutations, including 3 pathogenic variants in kinase domain, 3 pathogenic variants in helical domain, and 2 variants of unknown significance, in the endocrine-resistant group, while 3 (33%) of 9 patients displayed PIK3CA mutations, including 2 pathogenic variants in kinase domain and 1 pathogenic variant in helical domain, in the endocrine-sensitive group. In the endocrine-sensitive group, copy number gain of C11orf30 (EMSY) gene, copy number loss of CDH1 (E-cadherin) gene, and a missense mutation of splicing factor 3b (SF3B1) gene were also detected, which would probably decrease the expression of ESR1 and contribute to endocrine sensitivity. Collectively, the PIK3CA mutation rate in the resistance group is relatively higher than that in the sensitive group and thus PIK3CA mutations may contribute the primary endocrine resistance of breast cancer., Competing Interests: None., (IJCEP Copyright © 2018.)