Background:Giant phyllodes tumors are rare and are characterized by rapid growth and abundant vascularity. Intraoperative hemorrhage constitutes a major surgical challenge. This report describes a case of a 36-year-old woman with a giant phyllodes tumor of the breast, along with the corresponding treatment strategy. Case Description:A 36-year-old woman presented with a right mass for 2 years. Mammography showed a mass measuring 178 mm × 113 mm in the right breast, which was categorized as Breast Imaging Reporting and Data System (BI-RADS) 4C. Core needle biopsy suggested a possible phyllodes tumor. Following multidisciplinary team (MDT) consultation and recommendations from specialists in oncology and plastic surgery experts, preoperative embolization of the main feeding arteries was performed to minimize intraoperative hemorrhage, followed by intraoperative circumferential suture ligation of subcutaneous blood vessels. A mass weighing 4.42 kg was completely resected. Postoperative pathology showed extensive hemorrhagic degeneration and infarction of the tumor, with focal brisk stromal cellular proliferation; borderline change could not be excluded. The patient's postoperative recovery was uneventful. Conclusions:The "two-step" hemostatic strategy combining preoperative arterial embolization and intraoperative circumferential suture ligation can effectively reduce intraoperative bleeding in patients with giant phyllodes tumors. This approach is thus both feasible and safe for similar cases.

BackgroundAs breast cancer treatment advances, therapeutic efficacy has improved significantly, but cardiovascular toxicity from anticancer agents has become a critical concern. Elderly patients often have pre-existing cardiovascular comorbidities like coronary heart disease (CHD) and high venous thromboembolism (VTE) risk, requiring long-term antithrombotic therapy. Perioperative management demands individualized assessment of thrombotic and bleeding risks, with bridging anticoagulation when necessary. Close surveillance for cardiovascular complications (myocardial injury, heart failure, hypertension [HTN]) and control of modifiable risk factors (HTN, diabetes mellitus [DM]) are essential during treatment.Case reportThis study presents a breast cancer patient with multiple cardiovascular comorbidities (HTN, DM, CHD). Following multidisciplinary team (MDT) consultation, the low-cardiotoxicity PTD regimen (pertuzumab, trastuzumab, docetaxel) was selected. Perioperatively, aspirin was withheld, and low-molecular-weight heparin (LMWH) bridging was used 24 h before and after radical mastectomy. Postoperative radiotherapy was administered, with regular cardiac function monitoring throughout treatment. No cardiovascular complications occurred.ConclusionFor cancer patients with cardiovascular comorbidities, balancing tumor treatment and cardiovascular safety is achievable through comprehensive baseline risk assessment, the selection of low-cardiotoxicity regimens, rational perioperative antithrombotic adjustments, and continuous cardiac monitoring, thereby ensuring optimal oncological outcomes with minimized cardiovascular risks.

Background: Giant phyllodes tumors are rare and are characterized by rapid growth and abundant vascularity. Intraoperative hemorrhage constitutes a major surgical challenge. This report describes a case of a 36-year-old woman with a giantphyllodes tumor of the breast, along with the corresponding treatment strategy. Case Description: Case Description: A 36-year-old woman presented with a right mass for two years. Mammography showed a mass measuring 178 & times; 113 mm in the right breast, which was categorized as Breast-ImagingReportingandDataSystem(BI-RADS)4C. Core needle biopsy suggested a possible phyllodes tumor. Following multidisciplinary team (MDT) consultation and recommendations from specialists in oncology and plastic surgery experts, preoperative embolization of the main feeding arteries was performed to minimize intraoperative hemorrhage, followed by intraoperative circumferential suture ligation of subcutaneous blood vessels. A mass weighing 4.42 kg was completely resected. Postoperative pathology showed extensive hemorrhagic degeneration and infarction of the tumor, with focal brisk stromal cellular proliferation; borderline change could not be excluded. The patient's postoperative recovery was uneventful. Conclusion: The "two-step" hemostatic strategy combining preoperative arterial embolization and intraoperative circumferential suture ligation can effectively reduce intraoperative bleeding in patients with giant phyllodes tumors. This approach is thus both feasible and safe for similar cases.

Papillary thyroid carcinoma (PTC) is prone to metastasis, and patients with metastatic PTC have a poor prognosis. This study aimed to investigate the function of GLOD4 in PTC. Cancerous and paracancerous tissues were collected from patients with PTC. CO-IP was performed to detect the level of GLOD4 or ubiquitination modification, as well as to verify protein interactions of GLOD4 with UCHL1 or GLO1. Cell proliferation was detected by CCK-8 or EdU staining, cell migration and invasion by transwell assay, GLO1 enzyme activity by ELISA, total and mitochondrial methylglyoxal levels by commercial kits, mitochondrial ROS levels by flow cytometry, and oxygen consumption rate and ATP levels by seahorse energy metabolism analyzer. GLOD4 knockdown subcutaneous xenograft model was constructed in nude mice, HE staining was used to detect the histopathological condition of the tumor, and IHC was used to detect Ki67 and GLOD4 expression. GLOD4 levels were significantly upregulated in PTC tissues and cells, and overexpression of GLOD4 enhanced PTC cell proliferation, migration, and invasion. Mechanistically, UCHL1 could directly bind to GLOD4 and enhance its protein stability by promoting K48-linked deubiquitination, whereas the ability of GLOD4 to promote invasion and migration in PTC cells depends on this regulatory function of UCHL1. Furthermore, GLOD4 regulated GLO1 to detoxify methylglyoxal, a toxic by-product of glycolysis, to maintain mitochondrial homeostasis. GLOD4 knockdown inhibited PTC tumor growth in vivo. UCHL1 enhances the protein stability of GLOD4 through deubiquitination, promoting its interaction with GLO1 to cooperatively detoxify methylglyoxal, maintain mitochondrial homeostasis, and ultimately drive PTC progression.

PURPOSE:Several cyclin-dependent kinase 4/6 (CDK4/6) inhibitors have been approved for the treatment of hormone receptor-positive (HR+) and human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer. Despite the side effects that affect patients' quality of life, most patients still opt for CDK4/6 inhibitors due to their significant benefits. However, to further enhance treatment efficacy and safety, new approaches are still needed. PATIENTS AND METHODS:This multicentre, open-label, Phase 1 trial enrolled Chinese patients with HR+, HER2-advanced breast cancers. The primary endpoints were dose-limiting toxicity (DLT), maximum tolerated dose (MTD). Secondary endpoints included the objective response rate (ORR), clinical benefit rate (CBR), progression-free survival (PFS), and pharmacokinetic parameters. RESULTS:During the dose-escalation phase, a DLT was observed in the 150 mg bid dose cohort, specifically, 2 patients experienced grade 4 neutropenia. MTD of BEBT-209 was 100 mg bid, and the most common adverse event (AE) was neutropenia. In Phase 1b, the median PFS of patients with BEBT-209 alone, BEBT-209 plus letrozole, and BEBT-209 plus fulvestrant was 10.38 months, 24.94 months, and not reached, respectively. At doses of 25 mg qd-150 mg bid, steady state areas under the concentration-time curve and peak concentration increased proportionally with dose. The most common grade 3 or 4 AEs were neutropenia (65.4 %), lymphocytopenia (7.4 %), and anaemia (4.9 %). CONCLUSION:BEBT-209 was a primary CDK4 selective inhibitor and showed an acceptable safety profile and dose-dependent plasma exposure. The results highlight the potential of combination treatments as compelling options, particularly in combination with fulvestrant.

The tumor microenvironment (TME) and aberrant glycosylation have been suggested to play key roles in cancer. This study integrated differentially expressed genes (DEGs) and weighted gene coexpression network analysis (WGCNA) to identify tumor microenvironment-related genes and construct a TME-risk prognostic signature (TMERS) through LASSO Cox regression. After batch effect removal, 44 TME-prognosis-related genes (TMEPGs) were identified and classified into three molecular subtypes via K-means clustering. The finalized 22-gene TMERS model demonstrated robust prognostic predictive capacity in GEO datasets. The results revealed distinct immune profiles and prognostic stratifications among genetic subtypes and risk groups, confirming that the TMERS is an independent prognostic indicator for breast cancer (BRCA). Glycosyltransferase genes (GTs) have potential therapeutic relevance through immune regulation, with TMEPG member killer cell lectin like receptor B1 (KLRB1) significantly correlated with BRCA prognosis. Cellular experiments demonstrated that KLRB1 overexpression suppressed BRCA cell proliferation and migration. This work establishes a novel prognostic model for BRCA while highlighting KLRB1 as a potential biomarker, providing new insights into TME-targeted therapeutic strategies.

Background:Hand-foot syndrome (HFS) and oral mucositis (OM) are common adverse events during cancer chemotherapy and can significantly decrease patients' quality of life and chemotherapy adaptation, however, prevention strategies of these complications yet to be established. Methods:Patients with stages I-III breast cancer, who had surgery and needed pegylated liposomal doxorubicin (PLD)-based adjuvant chemotherapy were screened, recruited and randomly assigned to receive either probiotics or placebo (three capsules, twice/day) treatment during the course of chemotherapy from November 2019 to August 2020. The incidence and severity of PLD related HFS and OM, and patients' quality of life were assessed. Their plasma biomarkers, metabolites and fecal microbiota compositions were measured. And the results were further verified in animal experiments. Results:Probiotics supplement during PLD treatment significantly decreased the incidence and the severity of HFS and OM (P < 0.001), improved patients' life quality (P < 0.001), increased the relative abundance of intestinal Enterococcus (P = 0.025) and mitigated the changes of seven plasma metabolites. Among these metabolites, the changes of p-Mentha-1,8-dien-7-ol (MDO) (B = - 0.441, P = 0.02) and L-arginine (B = - 0.586, P = 0.002) were negatively correlated with the occurrence of severe HFS and OM. MDO can partly reproduce the preventive effects of probiotics on PLD-related skin cell proliferating inhibition, DNA damage, and local inflammation in rats. Conclusion:Probiotics supplement during PLD-based chemotherapy prevents the incidence and severity of HFS and OM, which may be associated with modulating plasma metabolites including the MDO.

Breast cancer (BC) is the most common malignancy in women and the leading cause of cancer death. Microplastics (MPs) are plastic fragments with a diameter of less than 5 mm, easily ingested by organisms. Although MPs have been reported to enter the human body through diet, surgery, etc., whether MPs accumulate in BC and their effects have been largely unknown. Our study revealed a significant accumulation of MPs in BC patient samples. MPs pull-down experiments and mass spectrometry (MS) studies showed that MPs bound to annexin A2 (ANXA2) and were endocytosed into cells. This process resulted in mitochondrial damage and subsequent induction of mitophagy. Furthermore, after binding to ANXA2, MPs regulated mitophagy by inhibiting IL-17 exocytosis. These findings revealed the mechanism of toxic effects of MPs in patients with BC, clarified the molecular mechanism of ANXA2-IL-17 signaling pathway causing mitochondrial damage by MPs, and suggested the potential toxic effects and toxicological mechanisms of MPs.

Understanding the factors that contribute to variability in breast cancer-related lymphedema (BCRL) is an important first step in developing targeted interventions to improve quality of life in breast cancer patients. Although previous research studies have has identified many risk factors for BCRL, dietary habits and catheterization type have rarely been studied until the present. This study aims to explore the effects of nursing factors such as dietary habits and catheterization type on breast cancer-related lymphedema (BCRL). This retrospective cohort study included 1,476 breast cancer patients who underwent surgery between January 1, 2012, and September 1, 2020. Lymphedema was assessed with a validated self-report questionnaire. All research data were obtained from medical records and a follow-up database. Multivariate Cox regression was conducted to explore the effects of dietary habits and catheterization type on BCRL. The results showed an increased risk for BCRL among breast cancer patients who followed a high-fat diet prehospitalization (HR = 2.47; 95

Background: Triple-negative breast cancer (TNBC) is a subtype of BC with high rates of mortality. The mechanism of PTPRG-AS1 in ferroptosis of TNBC was investigated. Methods: Chromatin immunoprecipitation and dual-luciferase reporter assays were used to measure intermolecular relationships. MTT and colony formation assays detected cell viability and proliferation. Kits detected Fe2+ and reactive oxygen species levels. The role of PTPRG-AS1 in tumor growth was analyzed in vivo. Results: PTPRG-AS1 was increased in TNBC tissues and cells. PTPRG-AS1 silencing increased the reduction of glutathione and GPX4, increased Fe2+ and reactive oxygen species in erastin-treated cells and inhibited proliferation. POU2F2 transcriptionally upregulated PTPRG-AS1. PTPRG-AS1 targeted miR-376c-3p to upregulate SLC7A11. PTPRG-AS1 knockdown suppressed tumor growth in vivo. Conclusion: POU2F2 transcriptionally activates PTPRG-AS1 to modulate ferroptosis and proliferation by miR-376c-3p/SLC7A11, promoting TNBC.

Background: Docetaxel is an important chemotherapy-agent for breast cancer treatment. One of its side-effects is weight gain, which increases the all-cause mortality rate. Considering gut microbiota is one important factor for weight regulation, we hypothesized that probiotics could be potentially used to reduce the docetaxel-related weight gain in breast cancer patients. Methods: From 10/8/2018 to 10/17/2019, 100 breast cancer (Stage I-III) patients underwent four cycles of docetaxel-based chemotherapy were enrolled and randomly assigned to receive probiotics (Bifidobacterium longum, Lactobacillus acidophilus, and Enterococcus faecalis) or placebo (supplementary material of the probiotics capsule) treatment for 84 days with three capsules per time, twice/day. The primary outcome: the changes in body weight and body-fat percentage of the patients were measured by a designated physician using a fat analyzer, and the secondary outcomes: the fasting insulin, plasma glucose, and lipids were directly obtained from the Hospital Information System (HIS); The metabolites were measured using liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS); The fecal microbiome was analyzed using bacterial 16S ribosomal RNA (rRNA) gene sequence. All indicators were measured 1 day before the first cycle of docetaxel-based chemotherapy and 21 days after the last cycle of docetaxel-based chemotherapy. Results: Compared with the placebo group, the probiotic group showed significantly smaller changes in body weight (Mean [SD] 0.77 [2.58] vs. 2.70 [3.08], P = 0.03), body-fat percentage (Mean [SD] 0.04 [1.14] vs. 3.86 [11.09], P = 0.02), and low density lipoprotein (LDL) (Mean [SD]−0.05[0.68] vs. 0.39 [0.58], P = 0.002). Moreover, five of the 340 detected plasma metabolites showed significant differences between the two groups. The change of biliverdin dihydrochloride (B = −0.724, P = 0.02) was inverse correlated with weight gain. One strain of the phylum and three strains of the genus were detected to be significantly different between the two groups. Also, the changes of Bacteroides (B = −0.917, P < 0.001) and Anaerostipes (B = −0.894, P < 0.001) were inverse correlated with the change of LDL. Conclusions: Probiotics supplement during docetaxel-based chemotherapy for breast cancer treatment may help to reduce the increase in body weight, body-fat percentage, plasma LDL, and minimize the metabolic changes and gut dysbacteriosis. Clinical Trial Registration: http://www.chictr.org.cn/showproj.aspx?proj=24294, ChiCTR-INQ-17014181.

Background: Chemotherapy-related cognitive impairment (CRCI) is highly preva-lent in patients with cancer and is associated with poor outcomes and quality of life. To date, the management of CRCI remains a clinical challenge. Herein, we aim to determine the pre-ventive effects of probiotics on CRCI development and underlying mechanisms.Methods: We conducted a randomised, double-blind and placebo-controlled trial (ChiCTRINQ-17014181) of 159 patients with breast cancer and further investigated the underlying mechanism in a pre-clinical setting. From 2018 to 2019, patients with breast cancer (Stage I-III) who needed adjuvant chemotherapy were screened, enrolled and randomly assigned to receive either probiotics or placebo (three capsules, twice/day) during chemotherapy. Their cognition, anxiety and depression were assessed with well-established assays; their plasma biomarkers, metabolites and faecal microbiota compositions were measured. In addition, the systemic effects of the metabolites found in the clinical trial on long-term potentiation, synapse injury, oxidative stress and glial activation were assessed in rats.Results: Probiotics supplement significantly decreased the incidence of CRCI, improved the allover cognitive functions, changed the gut microbial composition and modulated nine plasma metabolite changes. Among these metabolites, p-Mentha-1,8-dien-7-ol, Linoelaidyl carnitine and 1-aminocyclopropane-1-carboxylic acid were negatively correlated with the occurrence of CRCI. Furthermore, probiotics supplement increased plasma p-Mentha-1,8dien-7-ol in rats. Administration of exogenous p-Mentha-1,8-dien-7-ol significantly alleviated chemotherapy-induced long-term potentiation impairment, synapse injury, oxidative stress and glial activation in the hippocampus of rats.Conclusion: Our data indicated that probiotics supplement prevents the occurrence of CRCI in patients with breast cancer via modulating plasma metabolites, including p-Mentha-1,8dien-7-ol. Trial registration: Chinese Clinical Trial Registry (ChiCTR-INQ-17014181) [http://www. chictr.org.cn/showproj.aspx?projZ24294].(c) 2021 Elsevier Ltd. All rights reserved.

OBJECTIVE:To evaluate the role of hormone receptor expression on endocrine therapy in patients with breast cancer.METHODS:The databases were used to collect the effect of high expression and low expression of hormone receptors on the efficacy of endocrine therapy in breast cancer. Two evaluators independently screened the literature based on preset inclusion and exclusion criteria. The quality of the article was evaluated using a modified Newcastle-Ottawa Scale (NOS) system. The survival data included in the literature were extracted and the ln(hazard ratio (HR)) and se[ln(HR)] of the overall survival (OS), disease-free survival (DFS), and recurrence-free survival (RFS) rates were calculated according to different level of hormone receptors. The RevMan 5.3 software was used to evaluate the meta-analysis.RESULTS:A total of 13 relevant literature were included in the study. There were 8318 estrogen receptor (ER)-positive and 7926 progesterone receptor (PR)-positive patients. Overall survival, DFS, and RFS rates in high expression of ER(+) patients were significantly higher in low expression of ER(+) patients (OS HR = .59, 95% confidence interval (CI): .46-.76, P < .0001; DFS HR = .62, 95%CI: .50-.76, P < .00001; RFS HR = .44, 95% CI: .33-.58, P < .00001). In patients with high expression of PR(+), OS, DFS, and RFS rates were significantly higher than those with low expression of PR(+) (OS HR = .66, 95% CI: .57-.78, P < .00001; DFS HR = .52, 95% CI: .42-.65, P < .00001; RFS HR = .24, 95% CI: .11-.53, P = .0004).CONCLUSION:The expression of ER and PR are powerful predictors of adjuvant endocrine therapy response. Breast cancer patients with high expression of hormone receptors benefit more from endocrine therapy and have better prognosis.

Background Contralateral neck lymph node metastasis is rare in primary breast cancer. Its clinical staging and treatment principles lack authoritative guidelines. A case of a 30-year-old breast cancer patient with contralateral neck lymph node metastasis is presented. The clinical treatment is discussed in combination with current research. Case presentation A 30-year-old woman presented with a right breast mass for 5 months and left neck lymph node enlargement for 5 days. Mammography showed a 33 mm*14.3 mm mass in the inner quadrant of the right breast. The ultrasound showed several hypoechoic nodules on the left side of the neck. Rapid intraoperative pathological examination diagnosed a right breast malignant tumor and poorly differentiated carcinoma of the left cervical lymph nodes. Then, right mastectomy was performed immediately. The patient was scheduled to undergo chemotherapy, molecular targeted therapy, radiotherapy and endocrine therapy after the operation. The long-term efficacy remains to be seen. Conclusion The infrequent presentation of breast cancer with metastasis to the contralateral neck lymph node can be challenging for standard therapies.

Background: This study was performed to explore the safety of breast cancer (BC) mastoscopic surgery from the perspective of immunity and adipokines. Method: A single-center, prospective, randomized controlled trial was carried out among 42 patients who had undergone surgery from December 2018 to July 2019. All patients were randomly divided into an open surgery group (n = 21) and a mastoscopic surgery group (n = 21). Flow cytometry was used to detect natural killer (NK), CD4(+) T cells, CD8(+) T cells, and regulatory T (Treg) cells in each group 1 d before surgery, 1 h after operation, and 1, 5, and 7 d after operation. The levels of serum leptin and adiponectin were detected by enzyme-linked immunosorbent assay before and after operation. Results: There were no significant differences in the percentages of NK (p = 0.984), CD4(+) T (p = 0.591), Treg (p = 0.676), and CD8 (+) T (p = 0.341) lymphocytes between the two groups during the perioperative period. There were no significant differences in the levels of serum leptin and adiponectin before and after operation between the two groups (all p > 0.05). There were no significant differences between patients undergoing open surgery and mastoscopic surgery from the perspective of immunity and adipokines. Conclusion: Mastoscopic surgery is a suitable surgical choice for patients with BC.

We aimed to identify a signature comprising N6-methyladenosine (m6A)-related long non-coding RNAs (lncRNAs) and molecular subtypes associated with breast cancer (BRCA). We obtained data of BRCA samples from The Cancer Genome Atlas database. The m6A-related lncRNA prognostic signature (m6A-LPS) included 10 lncRNAs previously identified as prognostic m6A-related lncRNAs and was constructed using integrated bioinformatics analysis and validated. Accordingly, a risk score based on the m6A-LPS signature was established and shown to confirm differences in survival between high-risk and low-risk groups. Three distinct genotypes were identified, whose characteristics included features of the tumor immune microenvironment in each subtype. Our results indicated that patients in Cluster 2 might have a worse prognostic outcome than those in other clusters. The three genotypes and risk subgroups were enriched in different biological processes and pathways, respectively. We then constructed a competing endogenous RNA network based on the prognostic m6A-related lncRNAs. Finally, we validated the expression levels of target lncRNAs in 72 clinical samples. In summary, the m6A-LPS and the potentially novel genotype may provide a theoretical basis for further study of the molecular mechanism of BRCA and may provide novel insights into precision medicine.

[This corrects the article DOI: 10.3389/fonc.2020.00811.].

目的 探索适合低年级医学生的早接触临床见习模式.方法 通过调查问卷,对中南大学湘雅医学院2018级本科学生635名进行研究.结果 早期接触临床见习应包括的具体内容主要与医生基本工作有关;时间安排上学生认为观摩时间在20～30分钟较为合适,技能培训时间需50～100分钟;早期接触临床见习有利于医学生对临床工作的认识,但对临床思维的培养还有待提高.结论 对医学本科生开展早期接触临床见习很有必要,建立适合低年级医学生的早接触临床见习模式势在必行.

目的 探讨紫衫烷类与蒽环类药物用药顺序不同对乳腺癌新辅助化疗患者疗效的影响.方法 检索Pubmed、Cochrane、Embase、中国知网(CNKI)、万方医学网等数据库,收集符合纳入标准的研究.按纳入及排除标准由2名研究人员独立进行筛选、提取相关数据及质量评价.以5年总生存率(OS)、5年无病生存率(DFS)、病理完全缓解率(PCR)、保乳率、客观缓解率(ORR)、疾病控制率(DCR)及3～4级不良反应发生率作为观察指标.采用Revman5.3软件进行meta分析.结果 最终纳入符合标准的相关文献10篇,累计样本量1956例.先使用紫衫烷类药物再使用蒽环类药物(T→A组)患者OS、DFS、PCR、ORR、DCR、保乳率与先使用蒽环类再使用紫衫烷类药物(A→T组)比较,差异均无统计学意义(P>0.05).在3～4级不良反应中T→A组患者更易发生白细胞减少,差异有统计学意义(P=0.00001);两组患者其余3～4级不良反应比较,差异均无统计学意义(P>0.05).结论 乳腺癌新辅助化疗可考虑A→T的给药顺序.