The standard treatment for borderline and malignant phyllodes tumors is wide local excision (margins ≥1 cm), in the context of either breast-conserving surgery (BCS) or total mastectomy (TM). Due to the high risk of local recurrence (LR) following surgical intervention alone, the addition of adjuvant radiotherapy (RT) has been previously investigated; however, the conclusions have been inconsistent. This systematic review and meta-analysis was designed to assess the efficacy of adjuvant RT for borderline and malignant phyllodes tumors. Pubmed and Web of Science were systematically searched to identify relevant studies assessing the effect of adjuvant RT on borderline and malignant phyllodes tumors from the inception of this technique through May, 2014. A total of 8 studies were identified among 332 citations. In this meta-analysis, patients who received adjuvant RT had a lower relative risk of LR [hazard ratio (HR) = 0.43, 95% confidence interval (CI): 0.23-0.64]. The absolute risk difference was 10.1% (95% CI: 4.9-17.6), corresponding to a number needed to treat of 10. Our pooled meta-analysis clearly demonstrated a decreased risk of LR in patients with borderline and malignant phyllodes tumors who received RT following BCS (HR=0.31, 95% CI: -0.10-0.72). However, the combined HR for LR in the TM group did not demonstrate that adjuvant RT was superior to no RT (HR=0.68, 95% CI: -0.28-1.64). No significant differences were observed in overall survival (OS) or disease-free survival (DFS) between the two groups. Our analysis suggested that adjuvant RT for borderline and malignant phyllodes tumors decreased the LR rate in patients undergoing BCS. However, adjuvant RT was not found to exert an effect on OS or DFS.

MCTS1 re-initiation and release factor (MCTS1) is a ribosome-binding protein and shows multiple oncogenic properties in multiple cancers. This study aimed to investigate the expression, prognostic significance and transcription profile of MCTS1 in the PAM50 subtypes of breast cancer, as well as proteins with functional interactions with MCTS1 in luminal A/B breast cancer cells. Materials and Methods: Data from The Cancer Genome Atlas (TCGA)-Breast Carcinoma (BRCA) and Gene Expression Omnibus (GEO) and normal breast epithelial tissue data from the Genotype-Tissue Expression (GTEx) project were extracted and integrated for bioinformatic analysis. BT-474 and MCF-7 cells were used for in-vitro studies. Results: MCTS1 expression varied significantly among PAM50 subtypes. Its expression might independently predict unfavorable overall survival (OS) in luminal A and B cases, but not in other subtypes. ENST00000371317.9 is the dominant isoform of MCTS1 transcripts and showed a step increase from normal, adjacent normal to breast cancer tissues. The protein encoded by this isoform directly bound to TWF1 and synergistically modulated cyclin D1 and C-Myc translation in BT-474 and MCF-7 cells. Conclusion: MCTS1 expression might serve as a potential prognostic biomarker of unfavorable OS in luminal A and luminal B cases. The novel direct interaction between MCTS1 and TWF1 might be necessary for the translation of some downstream genes in common in luminal A/B breast cancer cells.

MORC4 has recently been characterized as a breast cancer-associated antiapoptotic oncoprotein. In the current study, we explored its downstream regulation in luminal A/B breast tumors. Materials and Methods: Bioinformatic prediction was performed using data from The Cancer Genome Atlas (TCGA)-breast cancer (BRCA). Cellular and molecular studies were conducted using luminal A/B representative MCF-7 and BT-474 cell lines. Results: ENST00000355610.8 (encoding MORC4a isoform) was the dominant transcript in breast cancer. ChIP-qPCR and dual-luciferase assay confirmed two STAT3-binding sites in the MID2 promoter in both MCF-7 and BT-474 cells. Co-IP confirmed an interaction between MORC4 and STAT3. ChIP-qPCR data indicated that MORC4 inhibition led to remarkably decreased enrichment of the STAT3-binding MID2 promoter segments. MORC4 overexpression significantly elevated BCL-2 expression in MCF-7 cells and increased their resistance to adriamycin (ADM), 5-fluorouracil (5-FU), and cisplatin (DDP). MID2 inhibition largely abrogated MORC4-induced drug-resistance. However, the drug-resistant phenotype was rescued by overexpressing MID2-MT that was resistant to MID2 siRNA. Conclusion: This study revealed a novel regulatory mechanism of MORC4 on MID2 expression via STAT3-mediated transcriptional activation. This regulatory axis might confer increased chemoresistance to breast cancer cells.

Background: MicroRNAs (miRNAs) representing a subclass of non-coding RNAs are dynamically expressed and participate in multiple pathological responses, whereas, the expression pattern or function of miRNAs has not been fully addressed in triple-negative breast cancer (TNBC). Currently we concentrate on dissecting the probable role of microRNA-663a (miR-663a) in TNBC cellular processes. Methods: qRT-PCR detected the expression of miR-663a in TNBC cells. Besides, we monitored the effects of miR-663a on TNBC proliferation and apoptosis. On the basis of bioinformatics assistance and mechanical validation, we identified the miRNA-sponging role of LINC01123 and downstream target of miR-663a in TNBC was assessed and verified. The transcription activation of was explored via ChIP and luciferase reporter assays. Results: In comparison to MCF-10A, we certified the downregulation of miR-663a in TNBC cell lines. Augmentation of miR-663a was anti-proliferation and pro-apoptosis in TNBC cell lines. LINC01123 protected CMIP against miR-663a suppression through acting as a sponge of miR-663a in TNBC. LINC01123 was transcriptionally induced by FOXC1. Rescue experiment proved that miR-663a suppression or CMIP (c-Maf inducing protein) enhancement could countervail LINC01123 depletion-mediated effects on TNBC cellular processes. Conclusion: LINC01123, activated by FOXC1, regulated TNBC growth through miR-663a/CMIP signaling, which unveiled a new functional pathway of FOXC1-induced LINC01123/miR-663a/CMIP in TNBC.