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The actin fiber-associated protein 1-antisense RNA1 (AFAP1-AS1) is upregulated in various cancers and associated with cancer proliferation and metastasis. Several cancer-related pathways have been linked to up-expression of this long non-coding (lnc)RNA, but the underlying mechanisms are yet unknown. In triple negative breast cancer (TNBC), AFAP1-AS1 expression is also significantly overexpressed compared to that in other subtypes of breast cancer from the TCGA dataset. In this study, we performed bioinformatic RNAhybrid analyses and identified that miR-145 is a potential target of AFAP1-AS1 and able to reduce MutT homolog-1 (MTH1) expression. Thus, this study investigated the oncogenic activity of AFAP1-AS1 in TNBC cells and the underlying mechanisms that are yet poorly understood. The results showed that miR-145 expression was low, whereas AFAP1-AS1 and MTH1 expression was high in TNBC cells and that miR-145 mimics reduced TNBC cell proliferation and invasion, whereas miR-145 knockdown exerted the opposite activity in TNBC cells. Moreover, knockdown of AFAP1-AS1 reduced tumor cell proliferation and invasion, but miR-145 co-transfection rescued tumor cell viability and colony formation ability. The dual luciferase reporter assay showed that AFAP1-AS1 could directly target miR-145, while miR-145 could directly target MTH1. After knockdown of ATF6, AFAP1-AS1 was reduced along with AFAP1-AS1 promoter activity. This study revealed that AFAP1-AS1 could promote TNBC cell proliferation and invasion via regulation of MTH1 expression through targeting of miR-145.

Purpose Triple-negative breast cancer (TNBC) pertains to a breast cancer subtype that has the highest metastatic and recurrence rates. The effectiveness of capecitabine as adjuvant chemotherapy for TNBC has remained unclear. This study conducted a meta-analysis of the efficacy of capecitabine as adjuvant chemotherapy for early-stage TNBC treated with taxane-/anthracycline-based chemotherapy. Methods We identified relevant research reports in online databases until May 2019. We finally included seven randomized clinical trials to perform this meta-analysis. Altogether, the seven trials enrolled 3151 early-stage TNBC patients, with 1552 receiving standard (neo)adjuvant chemotherapy regimens and 1599 receiving addition of capecitabine in the adjuvant settings besides standard regimens. Results A meta-analysis of the seven trials revealed a significant increase in disease-free survival (DFS) with the addition of capecitabine (Hazard ratio (HR) = 0.77, 95% CI 0.66–0.90). This improvement in DFS was significant both in trials conducted in America-Europe and in Asia. In trials involving six to eight cycles of capecitabine addition, we observed a significant improvement in DFS. Furthermore, in the meta-analysis of six trials, we detected a significant increase in overall survival (OS) favoring capecitabine (HR = 0.69, 95% CI 0.56–0.85). Conclusions Adjuvant addition of capecitabine to early-stage TNBC patients receiving standard chemotherapy showed significant DFS and OS improvement. Future studies involving the selection of patients that may have the highest survival benefit from adding capecitabine are warranted.

Long noncoding ribonucleic acids (LncRNAs) have been found to be involved in the proliferation, apoptosis, invasion, migration, and other pathological processes of triple-negative breast cancer (TNBC). Expression of the lncRNA actin filament-associated protein 1 antisense RNA1 (AFAP1-AS1) has been found to be significantly higher in TNBC than in other subtypes or in normal tissue samples, but the specific mechanism by which AFAP1-AS1 affects the occurrence and development of TNBC is yet to be revealed. In this study, we used Cell Counting Kit-8 (CCK-8), colony formation, wound healing migration, Transwell invasion, and nude mouse xenograft assays to confirm the role of AFAP1-AS1 in the proliferation, migration of TNBC cells in vitro and in vivo. In addition, we performed bioinformatics analyses, reverse transcriptase quantitative polymerase chain reaction (RT-qPCR), western blot (WB), and dual-luciferase reporter assays (dual-LRA) to confirm interaction among AFAP1-AS1, micro-RNA 2110 (miR-2110), and Sp1 transcription factor ( Sp1 ). We found that silencing AFAP1-AS1 and Sp1 or upregulating miR-2110 suppressed the proliferation, migration, and invasion of MDA–MB-231 and MDA–MB-468 cells in vitro as well as tumor growth in vivo. Mechanistically, the dual-LRA highlighted that miR-2110 was an inhibitory target of AFAP1-AS1, and that AFAP1-AS1 functioned as a miR-2110 sponge to increase Sp1 expression. AFAP1-AS1 silencing led to a reduction in Sp1 mRNA and protein levels, which could be reversed by joint transfection with miR-2110 inhibitor. Our findings demonstrated that AFAP1-AS1 could modulate the progression of breast cancer cells and affect tumorigenesis in mice by acting as a miR-2110 sponge, resulting in regulation of Sp1 expression. Therefore, AFAP1-AS1 could play a pivotal role in the treatment of TNBC.

Background The purpose of this study was to establish two preoperative nomogram models to evaluate the status of axillary lymph nodes (ALNs) in early breast cancer patients based on ultrasound data, PET/CT data, and clinicopathological features. Accordingly, more appropriate treatment strategies for breast cancer patients could be selected. Methods From April 2017 to April 2023, a total of 254 patients from the Clinical Data Research (CDR) database of Peking Union Medical College Hospital were included in this study and randomly assigned to the training and internal testing groups at a ratio of 8:2, with outcome variables being axillary lymph nodes metastasis (ALNM) and high nodal tumour burden (HNTB). The predictive factors determined by Least Absolute Shrinkage and Selection Operator (LASSO) regression and multivariate logistic regression analyses were used to construct the nomograms. Receiver operating characteristic (ROC) curves and calibration plots were used to assess the prediction models’ discrimination and calibration. Results LASSO regression and multivariate logistic regression analyses showed that Plnsuv (PET/CT lymph node SUVmax), unclear cortico-medullary delineation and Progesterone Receptor (PR) positive were independent predictors of ALNM. Moreover, Plnsuv, tumour size and Her-2 positive were independent predictors of HNTB, respectively. Integrating these independent predictors, two nomograms were successfully developed to accurately predict the status of ALN. For nomogram 1 (prediction of ALNM), the area under the ROC curve in the testing group was 0.889. For nomogram 2 (prediction of HNTB), the area under the ROC curve in the testing group was 0.784. The above results showed a satisfactory performance. Conclusions We developed two preoperative nomograms that can be used to predict ALN metastasis (LN − vs. LN+) and the number of metastatic ALNs (≤ 2 vs. >2) in early breast cancer patients. They were well verified in internal testing groups. The nomograms can help clinicians predict the status of ALNs and guide discussions regarding axillary management.

Background Intercellular communication is crucial for breast cancer progression and metastasis. However, the role of cancer-derived exosomes and their crucial microRNA (miRNA) cargoes mediating intercellular communication requires further investigation. Methods Cancer-derived exosomes were isolated using differential centrifugation and differentially expressed miRNAs were determined by microarrays and qRT-PCR analysis. Cell proliferation, wound-healing, Transwell invasion, and tumor xenograft assays were used for functional research. Plasma exosomal RNA was isolated to verify its role as a prognostic biomarker. Results We found that the tumor-promoting capacity of the exosomes was positively related to their cells of origin. MiR-7641 was identified to be the most differentially expressed miRNA, both at endogenous and secretory levels in high-metastatic cancer cells. MiR-7641 could promote tumor cell progression and metastasis, and that these functions of miR-7641 could alter recipient cells via transportation of exosomes. Additionally, exosomal miR-7641 could promote tumor growth in vivo; and its levels were significantly elevated in the plasma of patients with distant metastasis. Bioinformatics analysis has suggested that miR-7641 is correlated with breast cancer survival, and several important cellular and biological processes are closely targeted by miR-7641. Conclusion The findings indicate miR-7641 to be an important component of the cancer exosomes in promoting tumor progression and metastasis via intercellular communication. Additionally, exosomal miR-7641 may serve as a promising non-invasive diagnostic biomarker and potential targetable candidate in breast cancer treatment. BWySRQX9DMANyj4v-XQwBN Video Abstract

ObjectivesTo evaluate the prognostic value of osteoprotegerin (OPG), receptor activator of nuclear factor-κB (RANK) and RANK ligand (RANKL) of the RANK signalling in patients with breast cancer.DesignSystematic review and meta-analysis.Data sourcesWe searched the PubMed, Embase and Cochrane databases up to October 2024.Eligibility criteriaStudies of patients with primary breast cancer evaluating OPG, RANK or RANKL expression in relation to survival outcomes were included.Data extraction and synthesisData from eligible studies were extracted, and HRs with 95% CIs for overall survival (OS), metastasis-free survival (MFS) and disease-free survival (DFS) were used to assess prognostic value.ResultsA total of 18 studies, comprising 11 141 patients with primary breast cancer, were included in this analysis. Elevated OPG expression was found to be significantly associated with an increase in MFS (HR=0.59, 95% CI 0.44 to 0.80, p<0.001) in patients with breast cancer. Conversely, elevated RANK expression was associated with a statistically significant reduction in MFS (HR=1.74, 95% CI 1.26 to 2.40, p<0.001) and DFS (HR=1.34, 95% CI 1.06 to 1.68, p=0.01). No significant association was found between RANKL expression and MFS, DFS or OS after adjusting for publication bias.ConclusionsDownregulation of the RANK signalling predicts survival benefits in patients with primary breast cancer. Further investigation is warranted to explore the therapeutic potential of inhibiting RANK signalling in breast cancer.PROSPERO registration numberCRD42021234825.

Background Endocrine drugs may affect lipid metabolism in breast cancer (BC) patients. This study explores lipid changes in early-stage BC patients taking different endocrine drugs. Methods The changing trend of blood lipid during endocrine therapy in 2756 BC patients from January 2013 to December 2021 was retrospectively analyzed. The changes in four lipid parameters were assessed by the Generalized Linear Mixed Model, including total cholesterol (TC), triglycerides (TG), low-density lipoprotein (LDL-C), and high-density lipoprotein (HDL-C). These parameters were quantified at baseline and at 6, 12, 18, 24, 36, 48, 60, and 72 months after endocrine therapy initiation. Furthermore, a subgroup analysis according to menopausal status or medication types was conducted. Results A total of 1201 patients taking aromatase inhibitors (AIs), including anastrozole (ANA), letrozole (LET), or exemestane (EXE), and 1555 patients taking toremifene (TOR) were enrolled. TC and TG levels showed a significantly elevated trend during 5 years of treatment ( P  < 0.05). HDL-C levels increased from baseline in the TOR group ( P  < 0.05). Compared with the postmenopausal AI group, the increasing trends of TC, TG, and LDL-C in the premenopausal AI group were more evident with the extension of time (β = 0.105, 0.027, 0.086, respectively). Within 3 years, TC, TG, and LDL-C levels in the ANA and LET groups were significantly higher than baseline ( P  < 0.05). Moreover, the levels of TG in the EXE group were significantly lower than that in the ANA or LET group ( P  < 0.05), but this significant difference disappeared after 3 years. Conclusions AIs significantly influenced lipid profiles more than TOR. AIs had a greater effect on blood lipids in premenopausal patients. Steroidal AIs (EXE) may affect lipid levels less than nonsteroidal AIs (ANA and LET).

Breast cancer is the most common cancer among women worldwide. To evaluate the real-world effectiveness of Neo-adjuvant chemotherapy (NACT) and adjuvant chemotherapy (ACT), we conducted a retrospective study comparing their impact on breast cancer prognosis. We retrieved data from the SEER database. We applied propensity score matching (PSM) to minimize confounding factors. Breast-cancer specific survival (BCSS) and overall survival (OS) were compared between the two groups. We also developed a nomogram prognostic model using clinicopathological parameters to predict survival rates. We identified 46,447 eligible patients in the SEER database. After PSM, 9,025 patients were included in each group, with 11,762 patients receiving NACT and 34,685 undergoing ACT before PSM. In the PSM cohort, the 5-year BCSS and OS were 88.3% (95% CI: 87.6–89.0%) and 85.7% (95% CI: 84.9–86.5%) for the NACT group, respectively. Notably, patients in the ACT group showed significantly better survival prognosis compared to those in the NACT group. We also developed nomograms to predict the 3-year, 5-year, and 8-year OS and BCSS rates for patients receiving NACT or ACT. Breast cancer patients who undergo surgery followed by ACT have a more favorable prognosis compared to those receiving NACT before surgery.

Background Breast cancer (BC) is the leading cause of death among women, and epigenetic alterations that can dysregulate long noncoding RNAs (lncRNAs) are thought to be associated with cancer metabolism, development, and progression. This study investigated the epigenetic regulation of lncRNAs and its relationship with clinical outcomes and treatment responses in BC in order to identify novel and effective targets for BC treatment. Methods We comprehensively analysed DNA methylation and transcriptome data for BC and identified epigenetically regulated lncRNAs as potential prognostic biomarkers using machine learning and multivariate Cox regression analysis. Additionally, we applied multivariate Cox regression analysis adjusted for clinical characteristics and treatment responses to identify a set of survival-predictive lncRNAs, which were subsequently used for functional analysis of protein-encoding genes to identify downstream biological pathways. Results We identified a set of 1350 potential epigenetically regulated lncRNAs and generated a methylated lncRNA dataset for BC, MylnBrna, comprising 14 lncRNAs from a list of 20 epigenetically regulated lncRNAs significantly associated with tumour survival. MylnBrna stratifies patients into high-risk and low-risk groups with significantly different survival rates. These lncRNAs were found to be closely related to the biological pathways of amino acid metabolism and tumour metabolism, revealing a potential tumour-regulation function. Conclusion This study established a potential prognostic biomarker model (MylnBrna) for BC survival and offered an insight into the epigenetic regulatory mechanisms of lncRNAs in BC in the context of tumour metabolism.

To verify whether omitting radiotherapy from breast cancer treatment for patients ≥ 70 years old following breast-conserving surgery (BCS) without axillary lymph node dissection is safe. Previous studies have shown that omitting breast radiotherapy after BCS and axillary lymph node dissection is safe for elderly breast cancer patients. We aimed to evaluate the safety of BCS without axillary surgery or breast radiotherapy (BCSNR) in elderly patients with breast cancer and clinically negative axillary lymph nodes. We performed a retrospective analysis of 481 patients with breast cancer, aged ≥ 70 years, between 2010 and 2016. Of these, 302 patients underwent BCSNR and 179 underwent other, larger scope operations. Local recurrence rate, ipsilateral breast tumor recurrence (IBTR) rate, distant metastasis rate, breast-related death, disease-free survival (DFS), and overall survival (OS) were compared between the two groups. After a median follow-up of 60 months, no significant differences in local recurrence, distant metastasis rate, breast-related death, and DFS were noted. The OS was similar (P = 0.56) between the BCSNR group (91.7%) and other operations group (93.0%). The IBTR rate was considered low in both groups, however resulted greater (P = 0.005) in the BCSNR group (5.3%) than in other operations group (1.6%). BCSNR did not affect the survival of elderly patients with breast cancer with clinically negative axillary lymph nodes. IBTR was infrequent in both groups; however, there was a significant difference between the two groups. BCSNR is a feasible treatment modality for patients with breast cancer ≥ 70 years old with clinically negative axillary lymph nodes.