The correlation between systemic inflammatory markers and efficiency for advanced gastric cancer patients treated with ICIs combined with chemotherapy.

Currently lacking research to explore the correlation between inflammatory markers and the efficacy of immune checkpoint inhibitors (ICIs) combined with chemotherapy in the treatment of advanced gastric cancer. This study is a retrospective study and included patients with advanced gastric cancer who receiving ICIs combined with chemotherapy from January 2020 to December 2022. We analysed the relationship between systemic inflammatory markers and the efficacy of ICIs combined chemotherapy and constructed a clinical prediction model. A nomogram was constructed based on the results of the bidirectional stepwise regression model. A total of 197 patients were enrolled in the training group, with a median follow-up period of time 26 months. Kaplan Meier analysis showed that the median OS of patients with low systemic immune-inflammatory index (SII) and low platelet to lymphocyte ratio (PLR) was superior to those with high SII and PLR. Univariate and multivariate Cox regression analysis showed that SII, NLR, PLR, and N stage as independent prognostic factors for OS. Adding SII to the conventional model improved the predictive ability of the 12-month OS. A total of 95 patients were included in the validation group, and external validation of the SII-based nomogram showed favourable predictive performance. Baseline SII, PLR, and N stage may serve as independent predictive factors for survival outcomes in advanced gastric cancer patients undergoing ICIs combined with chemotherapy. The SII-based nomogram can provide intuitive and accurate prognosis prediction of individual patients.

Long-term survival after neoadjuvant therapy for triple-negative breast cancer under different treatment regimens: a systematic review and network meta-analysis.

BACKGROUND: Triple-negative breast cancer (TNBC) is a life-threatening subtype of breast cancer with limited treatment options. Therefore, this network meta-analysis (NMA) aimed to evaluate and compare the effect of various neoadjuvant chemotherapy (NCT) options on the long-term survival of patients with TNBC. METHODS: PubMed, Embase, Medline, Cochrane Library, Web of Science, and major international conference databases were systematically searched for randomized controlled trials (RCTs) on the efficacy of various NCT options in patients with TNBC. Searches were performed from January 2000 to June 2023. Study heterogeneity was assessed using the I2 statistic. Hazard ratios (HRs) and 95% confidence intervals (CIs) were used to evaluate disease-free survival (DFS) and overall survival (OS). Odds ratios (ORs) and 95% CIs were used to evaluate the pathologic complete response (pCR). The primary outcome was DFS. RESULTS: We conducted an NMA of 21 RCTs involving 8873 patients with TNBC. Our study defined the combination of anthracyclines and taxanes as the preferred treatment option. On this basis, the addition of any of the following new drugs is considered a new treatment option: bevacizumab (B), platinum (P), poly-ADP-ribose polymerase inhibitors (PARPi), and immune checkpoint inhibitor (ICI). Based on the surface under the cumulative ranking curve (SUCRA) values, the top three SUCRA area values of DFS were taxanes, anthracycline, and cyclophosphamide (TAC; 89.23%); CT (84.53%); and B (81.06%). The top three SUCRA area values of OS were CT (83.70%), TAC (62.02%), and B-containing regimens (60.06%). The top three SUCRA area values of pCR were B + P-containing regimens (82.7%), ICI + P-containing regimens (80.2%), and ICI-containing regimens (61.8%). CONCLUSIONS: This NMA showed that standard chemotherapy is a good choice with respect to long-term survival. Moreover, B associated with P-containing regimens is likely to be the optimal treatment option for neoadjuvant TNBC in terms of pCR.

Cytochrome b561 regulates iron metabolism by activating the Akt/mTOR pathway to promote Breast Cancer Cells proliferation.

Breast cancer (BC) is the leading cause of cancer-related mortality in women, necessitating the development of novel therapeutic targets. While cytochrome b561 (CYB561) expression is associated with poor prognosis in BC, the precise role of CYB561 in BC and its potential mechanisms remain unclear. In the present study, we found that CYB561 plays an essential role in BC growth. CYB561 expression was up-regulated in surgically resected cancerous tissues and in six BC cell lines. Lentivirus-mediated CYB561 knockdown in BC cells significantly reduced their proliferation, migration, and invasiveness. CYB561 participates in the regulation of iron metabolism in BC. CYB561 knockdown reduced total iron content, increased ferrous iron content, and down-regulated the expression of proteins associated with iron metabolism (transferrin receptor 1, divalent metal transporter 1, and ferritin heavy chain 1). Conversely, up-regulation of CYB561 through co-incubation with exogenous iron (ferric ammonium citrate) produced contrary outcomes. Additionally, CYB561 activated the protein kinase B/mammalian target of rapamycin (Akt/mTOR) signaling pathway in BC cells. Down-regulation of CYB561 expression inhibited the Akt/mTOR signaling pathway activity. The application of an mTOR agonist (MHY1485) rescued this negative effect, as well as the inhibitory effect of CYB561 knockdown on cell proliferation. Importantly, the dual mTOR inhibitor MLN0128 (50 nM, 48 h) down-regulated CYB561 expression and the iron metabolism-related proteins transferrin receptor, divalent metal transporter 1, and ferritin heavy chain 1, whereas the mTOR agonist MHY1485 rescued the down-regulation of CYB561 knockdown on iron metabolism-related proteins. We conclude that CYB561 promotes the proliferation of BC cells by regulating iron metabolism through the activation of the Akt/mTOR signaling pathway.

Screening Single Nucleotide Polymorphisms Predicting the Efficacy of Electroacupuncture for Fatigue Treatment in Patients with Breast Cancer Following Adjuvant Chemotherapy.

Chemotherapy-induced fatigue reduces not only the quality of life of patients but also effect their recurrence-free survival rate. Although electroacupuncture can relieve fatigue, it has limited affect on some patients. Therefore, appropriate biomarkers are needed to help screen patients who can benefit from electroacupuncture treatment of fatigue. We conducted this study to explore the predictive ability of SNPs on the efficacy of electroacupuncture in the treatment of fatigue in patients with breast cancer after adjuvant chemotherapy. Our study included breast cancer patients with fatigue after receiving paclitaxel and/or anthracycline based adjuvant chemotherapy. The patients were divided into the electroacupuncture group and the control group. The electroacupuncture treatment group received adjuvant chemotherapy and electroacupuncture treatment, while the control group only received adjuvant chemotherapy, and then compared the fatigue relief degree of two groups. In addition, we used NCBI dbSNP and PharmGKB databases to select fatigue related genes and their SNPs. We collected peripheral blood from the included patients for SNPs typing, and recorded the efficacy of electroacupuncture to analyzed the correlation between different SNPs and therapeutic efficacy. The side effects of electroacupuncture treatment were also recorded. 76 patients in the electroacupuncture group and 48 patients in the control group were enrolled. In the electroacupuncture group, 63 patients (82.9%) experienced moderate to severe fatigue (BFI score > 3). After electroacupuncture treatment, the number of patients with a BFI score of > 3 was 46 (60.5%). Therefore, the fatigue symptoms of 26.9% patients were significantly improved (P < 0.05). In the control group, which did not receive electroacupuncture treatment, 40 of 48 patients had a BFI score of > 3. Following the same observation time used in the electroacupuncture group, 36 patients had a BFI score of > 3 points. Thus, fatigue was not significantly relieved in the control group (83.3% vs. 75.0%, P > 0.05). We included 56 patients in our analysis of the correlation between SNPs and electroacupuncture treatment effects. We divided the patients into an effective group and ineffective group according to therapeutic effects. Our results indicated that the effective rate of electroacupuncture treatment with IL1A rs3783550 AC and CC genotypes was higher than that with other genotypes (AC: 84.6%, CC: 81.8%, AA: 33.0%, P < 0.05). Similarly, the effective rate of electroacupuncture treatment with HTR1A rs6295 GG and CC genotypes was higher than that with other genotypes (GG: 63.0%, CC: 55.6%, GC: 18.2%, P < 0.05). However, no other genotypes were related to the effect of electroacupuncture treatment on fatigue. Our result showed that electroacupuncture has therapeutic effect on fatigue after adjuvant chemotherapy for breast cancer and the side effects are tolerable. In addition, IL1A rs3763550 and HTR1A rss6295 can predict the therapeutic effect of electroacupuncture on fatigue after adjuvant chemotherapy in breast cancer, which helps to better screen patients who can benefit from electroacupuncture treatment.

Palbociclib plus endocrine therapy in hormone receptor-positive and HER2 negative metastatic breast cancer: a multicenter real-world study in the northwest of China.

BACKGROUND: Real-world data of Palbociclib are insufficient in China. This study aimed to investigate the treatment pattern and real-world outcomes in hormone receptor positive and human epidermal growth factor 2 receptor negative (HR+/HER2-) metastatic breast cancer (MBC) patients treated with Palbociclib in the northwest of China. METHODS: HR+/HER2- MBC patients who received Palbociclib in 8 centers from July 2017 to September 2019 were retrospectively included in this study. Real-world objective response rate (ORR), progression-free survival (PFS) and safety profiles were analyzed. The survival curves were plotted by the Kaplan-Meier method to analyze PFS, which was verified by the log-rank test. RESULTS: In total, 211 women were eligible for the analysis. A total of 85 patients (40.3%), 78 (37.0%), and 48 (22.7%) received Palbociclib in the first-, second-, third- or later-line setting, respectively. 46 patients achieved partial response and 145 patients experienced stable disease, with an ORR of 21.8% and a disease control rate of 90.5%. Following a median follow-up period of 14.2 months, the median PFS was 12.2 months (95% confidence interval, 10.1-14.3 m), and the median overall survival was not reached. Early Palbociclib initiation, sensitivity or acquired resistance to endocrine therapy, estrogen receptor and progesterone receptor double positivity, less than 3 metastatic sites, without visceral metastasis, bone metastasis only, without prior chemotherapy or endocrine therapy were associated with a prolonged PFS in MBC (All P < 0.05). The most common grade 3 or 4 adverse events (AE) was neutropenia (36.5%), and the most common nonhematologic AE was fatigue (10.9%). No patient experienced AE leading to treatment discontinuation. CONCLUSION: Palbociclib plus endocrine therapy exhibited favorable effectiveness and manageable toxicities in the real-world setting, supporting their use in Chinese patients with HR+/HER2 - MBC.

Therapeutic effect and metabolic fingerprinting of triple-negative breast cancer cells following exposure to a novel pH-responsive, gambogic acid-loaded micelle.

Triple-negative breast cancer (TNBC) is a subtype of breast cancer with a poor prognosis and lacks effective therapeutic targets. The use of gambogic acid (GA), a class of active ingredients in traditional Chinese medicine with anti-tumour potential, is limited in tumour therapy owing to its drawbacks and unclear organ toxicity. In this study, we used the pH-responsive amphiphilic block copolymer, PEOz-PCL, to create nanodrugs for GA delivery to MDA-MB-231 cells. The pH-responsive GA-loaded micelles were prepared through nanoprecipitation with a more homogeneous size. The average particle size was 42.29 ± 1.74 nm, and the zeta potential value was 9.88 ± 0.17 mV. The encapsulation rate was 85.06%, and the drug loading rate was 10.63%. The process was reproducible, and sustained release reached 80% in 96 h at acid pH 5.0. Furthermore, cellular tests using CCK-8, TUNEL, and flow cytometry revealed that pH-responsive GA-loaded micelles killed MDA-MB-231 cells more effectively and had much higher activity and targeting compared with free drugs. Metabolomic analysis of the changes in differential metabolites revealed that pH-responsive GA-loaded micelles may inhibit TNBC cells by causing amino acid anabolism, nucleotide metabolism, and glucose metabolism, as well as by affecting their energy sources. The study outcomes will help understand the mechanism of action and the therapeutic efficacy of pH-responsive GA-loaded micellesin vivo.

Meta-analysis of quality of life in patients with cancer treated with antibody-drug conjugates in randomized controlled trials.

Purpose: To evaluate the patient-reported outcomes of patients treated with commercially approved antibody-drug conjugates (ADC) reported in randomized controlled trials (RCT) published up to September 2023. Methods: A meta-analysis of 6430 patients from 12 randomized controlled trials was conducted. Results: No significant change was observed between the groups from baseline to end of treatment and end of follow-up, with a standardized mean difference of -0.08 (95% CI: -0.27-0.12) and 0.01 (95% CI: -0.11-0.12), respectively. Treatment with ADCs delayed the deterioration of patients' clinical condition compared with treatment with non-ADCs, with a hazard ratio of 0.78 (95% CI: 0.67-0.92). Conclusion: ADCs have a good correlation with delay of clinical deterioration in patients with cancer.

Updated efficacy of adjuvant epirubicin plus cyclophosphamide followed by taxanes versus carboplatin plus taxanes in early triple-negative breast cancer in phase 2 trial: 8.1-year median follow-up.

BACKGROUND: Paclitaxel/docetaxel after doxorubicin plus cyclophosphamide (ECT) is considered as an adjuvant chemotherapy and improves the survival of early triple-negative breast cancer (TNBC) patients. We aim to assess whether carboplatin plus taxanes (TP) is non-inferior to ECT in prolonging the survival time. METHODS: TNBC patients were randomized (1:1) to receive ECT (90 mg/m2 epirubicin + 600 mg/m2 cyclophosphamide followed by 75 mg/m2 docetaxel or 175 mg/m2 paclitaxel every 3 weeks, n = 154) or TP (75 mg/m2 docetaxel or 175 mg/m2 paclitaxel + carboplatin AUC 5 every 3 weeks, n = 154). These expression of SPARC, PD-L1, and BRCA were studied. Patients were followed up for disease-free survival (DFS), overall survival (OS), and safety. RESULTS: We recruited 308 TNBC patients (median follow-up of 97.6 months). The median DFS and OS were not reached; the 8-year DFS rate of ECT and TP arms was 78.4% and 81.7%, respectively, while the 8-year OS rate were 87.2% and 89.1%, respectively. In the SPARC (> 50%) subgroup analysis, the TP arm had longer DFS (P = 0.049) and a tendency with better OS (P = 0.06) than ECT arm. No significant differences were observed in the DFS and OS between the ECT arm and TP arm in TNBC with SPARC (≤ 50%), PD-L1 (-) PD-L1 (+), and BRCA mutation or BRCA wild (all P values > 0.05). CONCLUSION: TP showed non-inferiority for DFS and OS compared with ECT in early TNBC. TP may be an effective alternative chemotherapy for TNBC patients whom the standard ECT regimen is not being used. TRAIL REGISTRATION: ClinicalTrials.gov identifier NCT01150513.

The role of capecitabine-based neoadjuvant and adjuvant chemotherapy in early-stage triple-negative breast cancer: a systematic review and meta-analysis.

BACKGROUND: The role of capecitabine in neoadjuvant and adjuvant chemotherapy for early-stage triple-negative breast cancer (TNBC) is highly controversial. Our meta-analysis was designed to further elucidate the effects of capecitabine on survival in early-stage TNBC patients and its safety. METHODS: PubMed, Embase, and papers presented at several main conferences were searched up to December 19, 2019, to investigate capecitabine-based versus capecitabine-free neoadjuvant and adjuvant chemotherapy in TNBC patients. Heterogeneity was assessed using I2 test, combined with hazard ratios (HRs) and odds ratios (ORs) with 95% confidence intervals (CI) computed for disease-free survival (DFS), overall survival (OS), and over grade 3 adverse events (AEs). RESULTS: A total of 9 randomized clinical trials and 3842 TNBC patients were included. Overall, the combined capecitabine regimens in neoadjuvant and adjuvant chemotherapy showed significantly improved DFS (HR = 0.75; 95% CI, 0.65-0.86; P < 0.001) and OS (HR = 0.63; 95% CI, 0.53-0.77; P < 0.001). In subgroup analysis, there were improvements in DFS in the groups with addition of capecitabine (HR = 0.64; 95% CI, 0.53-0.78; P < 0.001), adjuvant chemotherapy (HR = 0.73; 95% CI, 0.63-0.85; P < 0.001), and lymph node positivity (HR = 0.62; 95% CI, 0.44-0.86; P = 0.005). Capecitabine regimens were related to higher risks of diarrhea (OR = 2.88, 95% CI 2.23-3.74, P < 0.001), stomatitis (OR = 2.01, 95% CI 1.53-2.64, P < 0.001) and hand-foot syndrome (OR = 8.67, 95% CI 6.70-11.22, P < 0.001). CONCLUSION: This meta-analysis showed that neoadjuvant and adjuvant chemotherapy combined with capecitabine significantly improved both DFS and OS in early-stage TNBC patients with tolerable AEs. There were benefits to DFS in the groups with the addition of capecitabine, adjuvant chemotherapy, and lymph node positivity.

Immune checkpoint inhibitors plus neoadjuvant chemotherapy in early triple-negative breast cancer: a systematic review and meta-analysis.

PURPOSE: Some studies have shown that Immune checkpoint inhibitors (ICIs) have a favorable efficacy in advanced triple negative breast cancer (TNBC) patients, but the results are controversial in neoadjuvant chemotherapy (NACT) stage. The purpose of this study is to evaluate the efficacy and safety after NACT plus ICIs in early TNBC patients. METHODS: After searching PubMed, EMBASE, the Cochrane library and several mainly oncology conferences up to 30 January 2021 systematically, and define randomized controlled trials (RCTs) exploring the efficacy and safety of programmed death protein-1/programmed cell death-Ligand 1(PD-1/PD-L1) inhibitors plus neoadjuvant chemotherapy in TNBC patients. The primary endpoint was the pathological complete response (pCR) in intention-to-treat populations (ITT), and the secondary endpoints were event-free survival (EFS) and safety analysis in the ITT populations. RESULTS: Six RCTs (N = 2142) were included in our meta-analysis; NACT plus ICIs increased pCR rates compared with NACT in intention-to-treat (ITT) populations (OR: 1.91; 95% CI: 1.32-2.78, P < 0.001). The pCR rate also increased in both PD-L1 positive (OR: 1.65; 95% CI: 1.26-2.16, P < 0.001) and PD-L1 negative patients (OR: 1.56; 95% CI: 1.04-2.33, P = 0.03), especially in PD-L1 positive patients. The benefit was also observed in nodal-positive populations (OR: 2.52; 95% CI: 1.69-3.77, P < 0.001) and Eastern Cooperative Oncology Group performance-status score (ECOG PS) 0 subgroup (OR: 1.90; 95% CI: 1.42-2.53, P < 0.001). Three RCTs (N = 1615) reported EFS and the results showed that adding PD-1/PD-L1 inhibitors increased EFS (HR 0.65, 95% CI 0.50-0.83, P = 0.0007) in ITT populations with a short follow-up time. In the safety analysis of 2205 patients with early TNBC from five eligible studies, NACT plus ICIs had a higher risk of grade 3-4 diarrhea (OR: 2.54; 95% CI: 1.21-5.32; P = 0.01), any grade of adverse effects(AEs)including vomiting (OR: 1.37; 95% CI: 1.00-1.86; P = 0.05), hyperthyroidism (OR: 6.04; 95% CI: 2.39-15.29; P < 0.001), and hypothyroidism (OR: 5.04; 95% CI: 3.02-8.39; P < 0.001). CONCLUSIONS: PD-1/PD-L1 inhibitors combined with chemotherapy can improve pCR rates and EFS, and with an increased incidence of some immune-related AEs compared with chemotherapy alone. NACT plus ICIs might be an option in patients with in PD-L1 positive and high-risk populations with positive nodal disease early TNBC.

A comparison between triplet and doublet chemotherapy in improving the survival of patients with advanced gastric cancer: a systematic review and meta-analysis.

BACKGROUND: Chemotherapy can improve the survival of patients with advanced gastric cancer. However, whether triplet chemotherapy can further improve the survival of patients with advanced gastric cancer compared with doublet chemotherapy remains controversial. This study reviewed and updated all published and eligible randomized controlled trials (RCTs) to compare the efficacy, prognosis, and toxicity of triplet chemotherapy with doublet chemotherapy in patients with advanced gastric cancer. METHODS: RCTs on first-line chemotherapy in advanced gastric cancer on PubMed, Embase, and the Cochrane Register of Controlled Trials and all abstracts from the annual meetings of the European Society for Medical Oncology (ESMO) and the American Society of Clinical Oncology conferences up to October 2018 were searched. The primary outcome was overall survival, while the secondary outcomes were progression-free survival (PFS), time to progress (TTP), objective response rate (ORR), and toxicity. RESULTS: Our analysis included 23 RCTs involving 4540 patients and 8 types of triplet and doublet chemotherapy regimens, and systematic review and meta-analysis revealed that triplet chemotherapy was superior compared with doublet chemotherapy in terms of improving median OS (HR = 0.92; 95% CI, 0.86-0.98; P = 0.02) and PFS (HR = 0.82; 95% CI, 0.69-0.97; P = 0.02) and TTP (HR = 0.92; 95% CI, 0.86-0.98; P = 0.02) and ORR (OR = 1.21; 95% CI, 1.12-1.31; P < 0.0001) among overall populations. Compared with doublet chemotherapy, subgroup analysis indicated that OS improved with fluoropyrimidine-based (HR = 0.80; 95% CI, 0.66-0.96; P = 0.02), platinum-based (HR = 0.75; 95% CI, 0.57-0.99; P = 0.04), and other drug-based triplet (HR = 0.79; 95% CI, 0.69-0.90; P = 0.0006) chemotherapies while not with anthracycline-based (HR = 0.70; 95% CI, 0.42-1.15; P = 0.16), mitomycin-based (HR = 0.81; 95% CI, 0.47-1.39; P = 0.44), taxane-based (HR = 0.91; 95% CI, 0.81-1.01; P = 0.07), and irinotecan-based triplet (HR = 1.01; 95% CI, 0.82-1.24; P = 0.94) chemotherapies. For different patients, compared with doublet chemotherapy, triplet chemotherapy improved OS (HR = 0.89; 95% CI, 0.81-0.99; P = 0.03) among Western patients but did not improve (HR = 0.96; 95% CI, 0.86-1.07; P = 0.47) that among Asian patients. CONCLUSIONS: Compared with doublet chemotherapy, triplet chemotherapy improved OS, PFS, TTP, and ORR in patients with advanced gastric cancer in the population overall, and improved OS in Western but not in Asian patients.

Phase II study of adjuvant chemotherapy with S1 plus oxaliplatin for Chinese patients with gastric cancer.

BACKGROUND: S-1 plus oxaliplatin(SOX) has been demonstrated to be effective and well tolerated for patients with metastatic gastric cancer. We conducted this phase II study to evaluate the feasibility of SOX as adjuvant chemotherapy for gastric cancer after curative resection. METHODS: Adjuvant chemotherapy consisted of six to eight cycles of S-1 plus oxaliplatin. Oxaliplatin was administered intravenously at a dose of 130 mg/m2 on day 1. S-1 was administered orally at a dose of 70 mg/m2 daily from day 1 to 14 of a 3-week cycle. A total of 58 patients were enrolled in this study. The primary end point of the trial was the treatment completion rate for six cycles. Secondary endpoints were safety, 1-year and 3-year of disease free survival (DFS) and overall survival (OS). RESULTS: A total of 58 patients were enrolled and 54 patients have been analysed. The completion rate of six cycles was 72.2%. Grade 4 toxicities included neutropenia (1.9%) and thrombocytopenia (3.7%). Grade 3 toxicities included leukopenia (5.6%), neutropenia (24.1%), thrombocytopenia (13.0%), nausea (7.4%), vomiting 13.0%), and diarrhea (13.0%). There was no grade 3 or higher peripheral sensory neuropathy and treatment-related death. The median follow-up time was 42.4 months. 1-year and 3-year DFS rate were 85.2 and 75.9%, respectively.1-year and 3-year OS were 98.1 and 85.2%, respectively. CONCLUSION: Adjuvant chemotherapy for GC with S-1 plus oxaliplatin is safe and feasible in Chinese patients. The optimal dose of oxaliplatin and optimal cycles of treatment still need to be further investigated. TRIAL REGISTRATION: clinicaltrials.gov identifier NCT01542294 . Trial registration date: 03/02/2012.

Safety and Efficacy of the S-1/Temozolomide Regimen in Patients with Metastatic Neuroendocrine Tumors.

PURPOSE: Both capecitabine alone and capecitabine in combination with temozolomide have activities against neuroendocrine tumors (NETs). However, the role of S-1 in NETs is still unknown. We performed a study to evaluate the safety and efficacy of the S-1/temozolomide (STEM) regimen in patients with locally advanced or metastatic NETs. METHODS: A retrospective review was conducted in 20 patients with locally advanced or metastatic NETs treated with the STEM regimen. Of the patients, 15 (75.00%) had failed 1 or more lines of treatment with somatostatin analogues, sunitinib, everolimus, anlotinib, or other chemotherapy regimens. The patients received S-1 at 40 mg/m2 orally twice daily on days 1-14 and temozolomide 200 mg orally once daily on days 10-14 of a 21-day cycle. The patients were followed up for evidence of object response, toxicity, and progression-free survival. RESULTS: Response to treatment was assessed using RECIST 1.1. Eight patients (40.00%) achieved a partial response (PR), and another 8 (40.00%) had stable disease (SD). The clinical benefit rate (PR and SD) was 80.00%. The median progression-free survival was not achieved. Only 1 patient (5.00%) had grade 3 adverse events. Among the patients with NETs of different origins, 4 (40.00%) and 5 (50.00%) with pancreatic NETs attained PR and SD, respectively. Four (40.00%) and 3 patients (30.00%) with nonpancreatic NETs attained PR and SD, respectively. CONCLUSIONS: The STEM regimen is exceptionally highly active and well tolerated in patients with locally advanced or metastatic NETs. Even in patients who showed disease progression with previous therapies, it is still highly active. In this 20-patient study, the regimen appeared to be similarly active in pancreatic endocrine tumors and nonpancreatic NETs.

Jinfu'an Decoction Inhibits Invasion and Metastasis in Human Lung Cancer Cells (H1650) via p120ctn-Mediated Induction and Kaiso.

BACKGROUND Previous research showed that Jin-Fu-An decoction has a significant effect on lung cancer. However, it remains unclear whether p120ctn and its transcription factor Kaiso play a role in lung cancer cell proliferation, adhesion, migration, and metastasis. MATERIAL AND METHODS Proliferation inhibition was detected by CCK-8 assay. The migration and invasion were detected using Transwell assay. The location and expression of p120ctn and Kaiso were monitored by immunofluorescence staining. The expression changes of p120ctn, its isoform 1A, its S288 phosphorylation, and Kaiso were measured by Western blot assay. RESULTS The lung cancer cell line H1650 administered Jin-Fu-An decoction had significantly reduced the growth in dose-dependent and time-dependent manners. Migration and metastasis were significantly inhibited by application of Jin-Fu-An decoction in a dose-dependent manner. Additionally, Jin-Fu-An decoction decreased the expressions of p120ctn, its isoform 1A, and its S288 phosphorylation, but the protein level of Kaiso was elevated. CONCLUSIONS Jin-Fu-An decoction inhibits the proliferation, adhesion, migration, and metastasis though down-regulation of p120ctn or its isoform 1A expression, mediating the up-regulation of Kaiso. The underlying mechanism of Jin-Fu-An decoction might involve targeting the lower expression of p120ctn S288 phosphorylation, which suggests that Jin-Fu-An decoction may be a potential therapeutic measure as prevention and control of recurrence and metastasis of lung cancer.

The Significance and Therapeutic Potential of GATA3 Expression and Mutation in Breast Cancer: A Systematic Review.

GATA3 is a critical transcription factor in the development of various human systems. The notion that GATA3 expression is required for the differentiation and maintenance of normal breast tissue has been well established. Recently, GATA3 is found to actively participate in the multistep process leading breast cancer pathogenesis, including tumorigenesis, tumor differentiation, epithelial mesenchymal transition, and metastasis through regulation of various target genes. On the other hand, several studies have raised questions and highlighted the role of GATA3-low or GATA3-negative cells during the malignant development of breast cancer. In addition to gene expression, GATA3 mutations provide another dimension of complexity. As one of the most frequently mutated genes in breast cancer, GATA3 mutations may have an effect on DNA-binding ability, protein production, and transactivation activity. Recognition of the multiple function of GATA3 in breast cancer will serve to deepen our understanding of the nature of this disease and develop novel therapeutic approaches.

Thyroid Metastases from Breast Cancer Case Report and Literature Review.

BACKGROUND: Thyroid metastasis arising from primary breast cancer is a rare phenomenon, with only a handful of cases documented in both national and international literature. The management approach and prognosis of this occurrence have sparked debates and uncertainties. CASE PRESENTATION: Herein, we report the case of a 55-year-old woman with breast cancer. She previously underwent extensive excision of the breast lesion with adjuvant chemotherapy and endocrine therapy. After 9 years, she presented with neck discomfort and examination suggested right thyroid metastasis and lymph node metastasis in the neck. Imaging showed pulmonary and bone metastases. Furthermore, the patient received endocrine therapy. After 7 months of follow- up, the patient survived without any new distant metastases. Thyroid metastases originating from breast cancer often unfold with a subtle, intricate nature, making early detection challenging. They tend to emerge inconspicuously, intertwining with widespread systemic metastases, hinting at a less favorable prognosis. CONCLUSION: Given the unusual clinical indicators, identifying heterochronic thyroid metastases in patients with tumors poses a distinct challenge, requiring clinicians to navigate the follow-up process with heightened sensitivity. The key lies in timely detection and early intervention, factors that can significantly enhance the overall quality of life for patients.

Third-line Treatment for Metastatic Triple-negative Breast Cancer: A Systematic Review and Network Meta-analysis.

OBJECTIVE: Metastatic triple-negative breast cancer (mTNBC) is an invasive histologic subtype with a poor prognosis and rapid progression. Currently, there is no standard therapy for the third-line treatment of mTNBC. In this study, we conducted a network meta-analysis to compare regimens and determine treatment outcomes. METHODS: We performed a systematic search of PubMed, EMBASE, the Cochrane Central Register of Controlled Bases, and the minutes of major conferences. Progression-free survival, overall survival, and objective response rate were analyzed through network meta-analysis using the R software (R Core Team). The efficacy of the treatment regimens was compared using hazard ratios, odds ratios, and 95% CIs. RESULTS: We evaluated 15 randomized controlled trials involving 6,010 patients. Compared with the physician's choice treatment, sacituzumab govitecan showed significant advantages in progression-free survival and overall survival, with hazard ratio values of 0.41 (95% CI: 0.32-0.52) and 0.48 (95% CI, 0.39-0.60). In terms of objective response rate, sacituzumab govitecan is the best-performing therapy (odds ratio: 10.82; 95% CI: 5.58-20.97). Adverse events among grades 3 to 5 adverse reactions, the incidence of neutropenia and leukopenia in each regimen was higher, whereas the incidence of fever, headache, hypertension, and rash was lower. CONCLUSION: Compared with the treatment of the physician's choice, sacituzumab govitecan appears more efficacious and is the preferred third-line treatment for mTNBC.

Validation of CTS5 Model in Large-scale Breast Cancer Population and Combination of CTS5 and Ki-67 Status to Develop a Novel Nomogram for Prognosis Prediction.

BACKGROUND: More than half of patients with early-stage estrogen receptor-positive (ER+) breast cancer relapse after completing 5 years of adjuvant endocrine therapy, so it is important to determine which patients are candidates for extended endocrine therapy. The clinical treatment score after 5 years (CTS5) is a prognostic tool developed based on postmenopausal ER+ breast cancer to assess the risk of late distant recurrence (LDR) after 5 years of adjuvant endocrine therapy for breast cancer. We aimed to externally validate the prognostic value of CTS5 in premenopausal and postmenopausal patients and combined with Ki-67 to develop a new model to improve the ability of prognosis prediction. METHODS: We included a total of 516 patients with early-stage ER+ breast cancer who had received 5 years of adjuvant endocrine therapy and were recurrence-free for 5 years after surgery. According to menopausal status, we divided the study population into 2 groups: premenopausal and postmenopausal women. The CTS5 of each patient was calculated using a previously published formula, and the patients were divided into low, intermediate, and high CTS5 risk groups according to their CTS5 values. Based on the results of the univariate analysis ( P <0.01), a multivariate COX proportional hazards regression analysis was conducted to establish a nomogram with significant variables ( P <0.05). The discriminative power and accuracy of the nomograms were assessed using the concordance index (C-index), calibration curve, and area under the time-dependent receiver operating characteristic curve. Discrimination and calibration were evaluated by bootstrapping 1000 times. Finally, we utilized decision curve analysis to assess the performance of our novel predictive model in comparison to the CTS5 scoring system with regard to their respective benefits and advantages. RESULTS: The median follow-up time was 7 years (6 to 9 years). The 516 women were categorized by CTS5 as follows: 246(47.7%) low risk, 179(34.7%) intermediate risk, and 91(17.6%) high risk. Using the CTS5 score as a continuous variable, patients' risk score was significantly positively associated with recurrence risk in both premenopausal and postmenopausal subgroups. For HER2- premenopausal patients and HER2+ postmenopausal patients, the CTS5 score was positively correlated with LDR risk. Patients with a Ki-67≥20% had a higher risk of LDR regardless of menopausal status. Using the CTS5 score as a categorical variable, the high-risk group of HER2- premenopausal patients had a higher risk of LDR. However, the CTS5 model could not distinguish the risk of LDR in different risk groups for HER2+ postmenopausal patients. In the high-risk group, patients with Ki-67≥20% had a higher risk of LDR, regardless of menopausal status. We developed a new nomogram model by combining the CTS5 model with Ki-67 levels. The C-indexes premenopausal and postmenopausal cohorts were 0.731 and 0.713, respectively. The nomogram model was well calibrated, and the time-dependent ROC curves indicated good specificity and sensitivity. Furthermore, decision curve analysis demonstrated that the new model had a wider and practical range of threshold probabilities, resulting in an increased net benefit compared with the CTS5 model. CONCLUSIONS: Our study demonstrated that the CTS5 model can effectively predict the risk of LDR in early-stage ER+ breast cancer patients in both premenopausal and postmenopausal patients. Extended endocrine therapy is recommended for patients with Ki-67≥20% in the CTS5 high-risk group, as well as premenopausal patients with HER2-. Compared with CTS5, the new nomogram model has better identification and calibration capabilities, and further research is required to validate its efficacy in large-scale, multicenter, and prospective studies.

Incidence rate of osteonecrosis of jaw after cancer treated with bisphosphonates and denosumab: A systematic review and meta-analysis.

OBJECTIVES: This study aimed to assess the overall incidence of osteonecrosis of the jaw (ONJ) caused by bisphosphonates and denosumab when used for controlling bone cancer metastasis or as adjuvant therapy. SUBJECTS AND METHODS: A systematic search of the PubMed, Embase, and Cochrane Library databases and major meetings' proceedings as of July 30, 2022, identified randomized controlled trials (RCTs) and observational trials that evaluated ONJ caused by denosumab or bisphosphonates. The total incidence and risk ratio (RR) for ONJ were calculated using a random-effects model. RESULTS: A total of 42 003 patients with various solid tumors reported in 23 RCTs were included. The overall ONJ incidence in cancer patients receiving denosumab or bisphosphonates was 2.08% (95% CI 1.37-2.91; p < .01; I2  = 94.99%). Patients receiving denosumab had a higher ONJ incidence than those receiving bisphosphonates (RR 1.64, 95% CI 1.10-2.44; p < .05; I2  = 65.4%). Subgroup analyses showed that prostate cancer patients receiving denosumab and receiving zoledronic acid had the highest ONJ incidences, 5.0% and 3.0%, respectively. The incidence of ONJ induced by different doses was also different. CONCLUSIONS: The incidence of ONJ caused by denosumab and bisphosphonates is low, the dose of the drug and the type of cancer have certain influence on ONJ. Therefore, clinicians should use the drug reasonably to improve the quality of life of patients.

Incidence of antibody-drug conjugate-related fatigue in patients with breast cancer: A systematic review and meta-analysis.

BACKGROUND: Numerous studies have reported the efficacy of antibody-drug conjugates (ADCs) for treating breast cancer. However, during cytotoxic drug treatment, long-term disabling fatigue is common. Moreover, studies in the relevant literature have indicated that fatigue can significantly increase the incidence of depression and sleep disorders. Therefore, this meta-analysis aims to evaluate the incidence of fatigue in breast cancer survivors treated with ADCs. METHODS: PubMed, EMBASE, Web of Science, and Cochrane Library databases were systematically searched for articles and conference abstracts published before March 16, 2023. Further, two authors independently extracted data from the included studies. The primary outcome of this study was the incidence of all-grade fatigue caused by the use of ADCs in patients with breast cancer. Finally, a random-effects model was used to calculate the incidence and 95% confidence intervals (CIs) of the outcome. RESULTS: Overall, 7963 patients from 31 studies were included in this meta-analysis to assess the incidence of fatigue caused by the use of approved and marketed ADCs in patients with breast cancer. Notably, the incidence of all-grade fatigue during ADC monotherapy was 39.84% (95% CI, 35.09%-44.69%). In subgroup analyses, among ADCs, the incidence of trastuzumab deruxtecan-induced fatigue was the highest, with an all-grade fatigue incidence of 47.05% (95% CI, 42.38%-51.75%). Meanwhile, the incidence of trastuzumab emtansine (T-DM1)-induced all-grade fatigue was 35.17% (95% CI, 28.87%-41.74%), which was the lowest among ADCs. Further, the incidence of all-grade fatigue due to sacituzumab govitecan was 42.82% (95% CI, 34.54%-51.32%), which was higher than that due to T-DM1. Moreover, the incidence of fatigue was higher with T-DM1 combination therapy than with monotherapy. CONCLUSIONS: Clinicians have highlighted the high incidence of ADC-related fatigue and its negative impact on patients' physical and mental health, making fatigue an important research variable. The results of this study will further contribute to a comprehensive understanding of ADCs, which have some clinical importance and are of great benefit to patients with breast cancer.