Effect of Adding Electroacupuncture to Standard Triple Antiemetic Therapy on Chemotherapy-Induced Nausea and Vomiting: A Randomized Controlled Clinical Trial.

PURPOSE: We aim to determine the effectiveness of adding electroacupuncture to standard triple antiemetic therapy for treating chemotherapy-induced nausea and vomiting (CINV). METHODS: From March 2022 to December 2023, a randomized, blind, sham-controlled trial conducted across six Chinese hospitals investigated patients with breast cancer undergoing highly emetogenic chemotherapy (HEC). Patients were randomly assigned to either true electroacupuncture (n = 120) or sham electroacupuncture (n = 119) groups, with both groups receiving standard triple antiemetic therapy. The primary end point was the proportion of complete protection (no vomiting, no need for rescue treatment, and no significant nausea, as evaluated using the visual analog scale [VAS]) within 120 hours after receiving HEC. RESULTS: Among 239 randomly assigned patients, 235 (98.3%) completed the trial. In the full analysis set, compared with the sham electroacupuncture group, the true electroacupuncture group demonstrated a significant increase in the complete protection rate from 34.5% to 52.9% (P = .004). Additionally, true electroacupuncture also showed enhanced total control (4.3% v 13.4%; P = .014), no significant nausea (37.9% v 58.8%; P = .001), no nausea (4.3% v 13.4%; P = .014), and nausea VAS score = 0 mm (4.3% v 12.6%; P = .023). However, the occurrence of no vomiting in the overall stage was similar (76.7% v 73.9%; P = .622) in both groups. Post hoc exploratory analysis showed a significantly higher rate of complete protection during the delayed stage in the true electroacupuncture group compared with the sham electroacupuncture group, with no significant difference observed during the acute stage. CONCLUSION: Adding true electroacupuncture to standard triple antiemetic therapy significantly enhances the efficacy of CINV treatment in patients with breast cancer receiving HEC.

Characteristics of a Novel Zearalenone Lactone Hydrolase ZHRnZ and Its Thermostability Modification.

Zearalenone (ZEN) is a toxic secondary metabolite produced by the Fusarium fungi, which widely contaminates grains, food, and feed, causing health hazards for humans and animals. Therefore, it is essential to find effective ZEN detoxification methods. Enzymatic degradation of ZEN is believed to be an eco-friendly detoxification strategy, specifically thermostable ZEN degradation enzymes are needed in the food and feed industry. In this study, a novel ZEN lactone hydrolase ZHRnZ from Rosellinia necatrix was discovered using bioinformatic and molecular docking technology. The recombinant ZHRnZ showed the best activity at pH 9.0 and 45 °C with more than 90% degradation for ZEN, α-zearalenol (α-ZOL), ß-zearalenol (ß-ZOL) and α-zearalanol (α-ZAL) after incubation for 15 min. We obtained 10 mutants with improved thermostability by single point mutation technology. Among them, mutants E122Q and E122R showed the best performance, which retained more than 30% of their initial activity at 50 °C for 2 min, and approximately 10% of their initial activity at 60 °C for 1 min. The enzymatic kinetic study showed that the catalytic efficiency of E122R was 1.3 times higher than that of the wild-type (WT). Comprehensive consideration suggests that mutant E122R is a promising hydrolase to detoxify ZEN in food and feed.

Cross-border regulation of the STK39/MAPK14 pathway by Lycium barbarum miR166a to inhibit triple-negative breast cancer.

OBJECTIVE: To investigate the effects of Lycium barbarum miRNA166a (Lb-miR166a) on human gene expression regulation during the therapy for triple-negative breast cancer (TNBC). METHODS: Transcriptome sequencing was used to analyze the distribution and composition of miRNA in Lycium barbarum fruit. Lb-miR166a was introduced into TNBC MB-231 cells by lentiviral transfection to study its effects on cell proliferation, apoptosis, invasion, and metastasis both in vivo and in vitro. Bioinformatic and dual-luciferase assays identified the target gene of Lb-miR166a. The role of STK39 in TNBC progression was elucidated through clinical data analysis combined with cellular studies. The influence of Lb-miR166a on the STK39/MAPK14 pathway was confirmed using a target-specific knockout MB-231 cell line. RESULTS: Lb-miR166a was found to be highly expressed in Lycium barbarum. It inhibited MB-231 cell proliferation, invasion, and metastasis, and promoted apoptosis. STK39 was overexpressed in TNBC and was associated with increased invasiveness and poorer patient prognosis. Gene enrichment analysis and dual-luciferase assays demonstrated that Lb-miR166a regulates STK39 expression cross-border and inhibits MAPK14 phosphorylation, impacting the phosphorylation of downstream target genes. CONCLUSION: The downregulation of STK39 and subsequent inhibition of MAPK14 phosphorylation by Lb-miR166a leads to reduced proliferation, migration, and invasion of TNBC cells. These findings suggest a novel therapeutic strategy for TNBC treatment, highlighting possible clinical applications of Lb-miR166a in managing this aggressive cancer type.

Clinicopathological characteristics and prognostic factors in invasive micropapillary carcinoma of the breast.

Introduction: Invasive micropapillary carcinoma (IMPC) treatment only relies on the standard treatment of nonspecific invasive breast cancer (NSIBC), and it remains controversial whether the survival of patients improves. Therefore, this study aimed to analyze the clinicopathological features of IMPC and to investigate the factors affecting its prognosis. Material and methods: This retrospective cohort study included 104 IMPC patients who met the study's inclusion criteria out of a total of 4,532 patients with invasive breast cancer between January 2015 and December 2019. A contemporaneous cohort of 230 patients with non-specific invasive breast cancer (NSIBC) who underwent surgery was identified and matched using propensity scores. Results: The survival rate for patients with IMPC ranged from 1.12% to 7.03%. Statistically significant differences were observed in the proportion of endocrine treatment, lymphatic invasion, estrogen receptor (ER)-positive rate, molecular subtypes, molecular typing, and 5-year loco-regional recurrence-free survival (LRRFS) between the two cohorts (p < 0.05). The univariate analysis showed that T stage, N stage, lymphatic invasion, vascular invasion, ER-positive rate, and progesterone receptor (PR)-negative rate were all prognosis risk factors (p < 0.05) for IMPC. Furthermore, the multivariate analysis indicated that lymphatic invasion and N stage were independent prognostic factors (p < 0.05). Conclusions: The incidence of micropapillary IMPC, among other pathological subtypes, is steadily increasing. ER-positive and PR-positive rates, as well as luminal subtypes, are frequent, with a concurrent increase in the 5-year locoregional recurrence rate. It would be interesting to compare the effect following these therapeutic modifications in larger cohorts in future studies.

A phase II study of efficacy and safety of the MEK inhibitor tunlametinib in patients with advanced NRAS-mutant melanoma.

BACKGROUND: NRAS-mutant melanoma is an aggressive subtype with poor prognosis; however, there is no approved targeted therapy to date worldwide. METHODS: We conducted a multicenter, single-arm, phase II, pivotal registrational study that evaluated the efficacy and safety of the MEK inhibitor tunlametinib in patients with unresectable, stage III/IV, NRAS-mutant melanoma (NCT05217303). The primary endpoint was objective response rate (ORR) assessed by independent radiological review committee (IRRC) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. The secondary endpoints included progression-free survival (PFS), disease control rate (DCR), duration of response(DOR), overall survival (OS) and safety. FINDINGS: Between November 2, 2020 and February 11, 2022, a total of 100 patients were enrolled. All (n = 100) patients received at least one dose of tunlametinib (safety analysis set [SAS]) and 95 had central laboratory-confirmed NRAS mutations (full analysis set [FAS]). In the FAS, NRAS mutations were observed at Q61 (78.9%), G12 (15.8%) and G13 (5.3%). The IRRC-assessed ORR was 35.8%, with a median DOR of 6.1 months. The median PFS was 4.2 months, DCR was 72.6% and median OS was 13.7 months. Subgroup analysis showed that in patients who had previously received immunotherapy, the ORR was 40.6%. No treatment-related deaths occurred. INTERPRETATION: Tunlametinib showed promising antitumor activity with a manageable safety profile in patients with advanced NRAS-mutant melanoma, including those who had prior exposure to immunotherapy. The findings warrant further validation in a randomized clinical trial.

The Role of Ki-67 in HR+/HER2- Breast Cancer: A Real-World Study of 956 Patients.

Objective: This study determined the cut-off value of Ki-67 expression and discussed the interaction between Ki-67 and histological grade, further explored the prognostic role of Ki-67 in hormone receptor-positive and human epidermal growth factor receptor 2 negative (HR+/HER2-) breast cancer;. Materials and Methods: We assessed the Ki-67 expression of 956 patients with HR+/HER2 breast cancer diagnosed in the General Hospital of Ningxia Medical University from 2015 to 2019 by immunohistochemistry (IHC), The disease-free survival (DFS) was defined as the time from postoperative to the first local recurrence, distant metastasis or death of the disease. The follow-up by means of inpatient or outpatient medical records and telephone. Results: 22.5% was used as the cut-off for low/high Ki-67 expression in HR+/HER2- breast cancer. Compared with the value of 14%, which is commonly used in clinic at present, the consistency of the two values is moderate (Kappa = 0.484, P<0.001). The expression of Ki-67 was increased with the grade. (Median: G1:10%; G2:20%; G3:40%. Mean: G1:13%; G2:23%; G3:39%, P <0.001). Survival analysis was based on all patients for a median of 51 months (24-89 months), 63 cases had recurrence or metastasis during the follow-up, which 21 cases had low expression of Ki-67 and 42 cases had high expression. The patients with Ki-67 ≥ 22.5% had a 2.969 higher risk of early recurrence and metastasis than the patients with Ki-67 < 22.5%. There were 4 cases of local recurrence, 7 cases of regional lymph node metastasis, and 52 cases of distant metastasis in all patients, the common distant metastases were bone, liver, and lung, and rare metastases were adrenal gland, bone marrow, and pericardium. Conclusion: In HR+/HER2- breast cancer, patients with Ki-67 > 22.5% have a worse prognosis and are more likely to have early recurrence and metastasis.

HPLC and LC-MS/MS-Based Quantitative Characterization of Related Substances Associated with Sotalol Hydrochloride.

In total, three related substances (RS) associated with sotalol hydrochloride (STHCl) were herein identified with a novel gradient high-performance liquid chromatography (HPLC) protocol. Further characterization of these substances was then performed via liquid chromatography-mass spectroscopy (LC-MS/MS) and nuclear magnetic resonance (NMR) approaches. For these analyses, commercial STHCl samples were used for quantitative HPLC studies and the degradation of STHCl under acidic (1M HCl), alkaline (1M NaOH), oxidative (30% H2O2), photolytic (4500 Lx), and thermal stress conditions (100 °C) was assessed. This approach revealed this drug to be resistant to acidic, alkaline, and high-temperature conditions, whereas it was susceptible to light and oxidation as confirmed through long-term experiments. The putative mechanisms governing RS formation were also explored, revealing that RS3 was derived from the manufacturing process, whereas RS2 was generated via oxidation and RS1 was generated in response to light exposure. The cytotoxicity of these RS compounds was then assessed using MTT assays and acute toxicity test. Overall, this study provides details regarding the characterization, isolation, quantification, and toxicological evaluation of STHCl and associated RS compounds together with details regarding the precise, specific, and reliable novel HPLC technique, thus providing the requisite information necessary to ensure STHCl purity and safety.

Toripalimab plus nab-paclitaxel in metastatic or recurrent triple-negative breast cancer: a randomized phase 3 trial.

The combination of immune-checkpoint blockade with chemotherapy for the first-line treatment of advanced triple-negative breast cancer (TNBC) has generated mixed results. TORCHLIGHT is a randomized, double-blinded phase 3 trial evaluating the efficacy and safety of first-line toripalimab and nab-paclitaxel (nab-P) (n = 353; experimental arm) versus placebo and nab-P (n = 178; control arm) for the treatment of women with metastatic or recurrent TNBC. The primary end point was progression-free survival (PFS) assessed by a blinded independent central review in the PD-L1-positive and intention-to-treat populations. The secondary end points included overall survival and safety. Overall, 200 and 100 patients, in the toripalimab and placebo arm respectively had PD-L1-positive TNBC. At the prespecified interim analysis, a statistically significant improvement in PFS assessed by a blinded independent central review was demonstrated in the experimental arm in the PD-L1-positive population (median PFS 8.4 versus 5.6 months; hazard ratio (HR) = 0.65, 95% confidence interval (CI) 0.470-0.906, P = 0.0102). The median overall survival was 32.8 versus 19.5 months (HR = 0.62, 95% CI 0.414-0.914, P = 0.0148). Similar incidences of treatment-emergent adverse events (AEs) (99.2% versus 98.9%), grade ≥3 treatment-emergent AEs (56.4% versus 54.3%) and fatal AEs (0.6% versus 3.4%) occurred in the experimental and control arms. The addition of toripalimab to nab-P provided a significant improvement in PFS for PD-L1-positive patients with metastatic or recurrent TNBC with an acceptable safety profile. ClinicalTrial.gov identifier NCT03777579 .

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.

Safety of COVID-19 Vaccination in Patients With Breast Cancer: Cross-Sectional Study in China.

BACKGROUND: The widespread use of vaccines against the novel coronavirus disease (COVID-19) has become one of the most effective means to establish a population immune barrier. Patients with cancer are vulnerable to COVID-19 infection, adverse events, and high mortality, and should be the focus of epidemic prevention and treatment. However, real-world data on the safety of vaccines for patients with breast cancer are still scarce. OBJECTIVE: This study aims to compare the safety of COVID-19 vaccines between patients vaccinated before or after being diagnosed with breast cancer. METHODS: Patients with breast cancer who sought medical advice from October 2021 to December 2021 were screened. Those who received COVID-19 vaccines were enrolled in this study to analyze the safety of the vaccines. The primary outcome was patient-reported adverse events (AEs). All events after vaccine injection were retrospectively documented from the patients. RESULTS: A total of 15,455 patients with breast cancer from 41 hospitals in 20 provinces in China were screened, and 5766 patients who received COVID-19 vaccines were enrolled. Of those enrolled, 45.1% (n=2599) of patients received vaccines before breast cancer diagnosis, 41.3% (n=2379) were vaccinated after diagnosis, and 13.6% (n=784) did not known the accurate date of vaccination or cancer diagnosis. Among the patients vaccinated after diagnosis, 85.4% (n=2032) were vaccinated 1 year after cancer diagnosis and 95.4% (n=2270) were vaccinated during early-stage cancer. Of all 5766 vaccinated patients, 93.9% (n=5415) received an inactivated vaccine, 3.7% (n=213) received a recombinant subunit vaccine, and 2.4% (n=138) received other vaccines, including adenovirus and mRNA vaccines. In the first injection of vaccines, 24.4% (n=10, 95% CI 11.2-37.5) of patients who received an adenovirus vaccine reported AEs, compared to only 12.5% (n=677, 95% CI 11.6-13.4) of those who received an inactivated vaccine. Patients with metastatic breast cancer reported the highest incidence of AEs (n=18, 16.5%, 95% CI 9.5-23.5). Following the second injection, patients who received an inactivated vaccine (n=464, 8.7%, 95% CI 8.0-9.5) and those who received a recombinant vaccine (n=25, 8.7%, 95% CI 5.5-12.0) reported the same incidence of AEs. No significant differences in patient-reported AEs were found between the healthy population and patients with breast cancer (16.4% vs 16.9%, respectively); the most common AEs were local pain (11.1% vs 9.1%, respectively), fatigue (5.5% vs 6.3%, respectively), and muscle soreness (2.3% vs 3.6%, respectively). The type of vaccine and time window of vaccination had little impact on patient-reported AEs. CONCLUSIONS: Compared with patients vaccinated before breast cancer diagnosis, there were no significant differences in patient-reported AEs in the patients vaccinated after diagnosis. Thus, it is safe for patients with breast cancer, especially for those in the early stage, to receive COVID-19 vaccines. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2200055509; https://tinyurl.com/33zzj882.

Treatment-related adverse events of antibody-drug conjugates in clinical trials: A systematic review and meta-analysis.

Background: The wide use of antibody-drug conjugates (ADCs) is transforming the cancer-treatment landscape. Understanding the treatment-related adverse events (AEs) of ADCs is crucial for their clinical application. We conducted a meta-analysis to analyze the profile and incidence of AEs related to ADC use in the treatment of solid tumors and hematological malignancies. Methods: We searched the PubMed, Embase, and Cochrane Library databases for articles published from January 2001 to October 2022. The overall profile and incidence of all-grade and grade ≥ 3 treatment-related AEs were the primary outcomes of the analysis. Results: A total of 138 trials involving 15,473 patients were included in this study. The overall incidence of any-grade treatment-related AEs was 100.0% (95% confidence interval [CI]: 99.9%-100.0%; I 2 = 89%) and the incidence of grade ≥ 3 treatment-related AEs was 6.2% (95% CI: 3.0%-12.4%; I² = 99%). Conclusions: This study provides a comprehensive overview of AEs related to ADCs used for cancer treatment. ADC use resulted in a high incidence of any-grade AEs but a low incidence of grade ≥ 3 AEs. The AE profiles and incidence differed according to cancer type, ADC type, and ADC components.

Steroidal Alkaloids from the Roots of Veratrum mengtzeanum Loes. with Their Anti-Inflammatory Activities.

The phytochemical investigation of Veratrum mengtzeanum Loes. roots resulted in the isolation and characterization of two novel, namely Mengtzeanines A (1), Mengtzeanines B (2), and eight known steroidal alkaloids (3-10). Their structural properties were assessed though extensive spectroscopic techniques. All constituents 1-10 were analyzed for suppression of NO formation in LPS-induced RAW264.7 macrophages. Among them, constituent 6 (Verazine) showed inhibition against LPS-induced NO production (IC50 = 20.41 µM). Additionally, compound 6 could inhibit the secretion of IL1ß, IL6, and TNFα, and downregulate the productions of iNOS and COX2 in LPS-induced RAW264.7 macrophages. Further experiments revealed that 6 exhibited a potent anti-inflammatory level in LPS-stimulated RAW264.7 macrophages via inhibiting NF-κB, and triggering of Keap1/Nrf2/HO-1 axis, implying that compound 6 may be a promising candidate for treating inflammatory disorders.

Role of SARS­CoV­2 nucleocapsid protein in affecting immune cells and insights on its molecular mechanisms.

The present study aimed to explore the immune regulatory function of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleocapsid (N) protein and related mechanisms. In a series of protein activity experiments, SARS-CoV-2 N protein promoted proliferation of three immune cell lines: mouse Raw264.7, human Jurkat and human Raji in a dose-dependent manner. A total of 10 µg/ml N protein could significantly change cell cycle progression of the aforementioned three immune cell lines and could promote quick entry of Raw264.7 cells into G2/M phase from S phase to achieve rapid growth. Additionally, the N protein could also stimulate Raw264.7 cells to secrete a number of proinflammatory factors such as TNF-α, IL-6 and IL-10. RNA sequencing analysis indicated that the N protein changed the expression of certain genes involved in immune-related functions and four important signaling pathways, including JAK-STAT, TNF, NF-κB and MAPK signaling pathways, which suggested that the N protein may not only regulate the expression of genes involved in the process of resisting viral infection in macrophages of the immune system, but also change cellular signal processing.

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.

Development of Tumor Markers for Breast Cancer Immunotherapy.

Although breast cancer treatment has been developed remarkably in recent years, it remains the primary cause of death among women. Immune checkpoint blockade therapy has significantly altered the way breast cancer is treated, although not all patients benefit from the changes. At present, the most effective mechanism of immune checkpoint blockade application in malignant tumors is not clear and efficacy may be influenced by many factors, including host, tumor, and tumor microenvironment dynamics. Therefore, there is a pressing need for tumor immunomarkers that can be used to screen patients and help determine which of them would benefit from breast cancer immunotherapy. At present, no single tumor marker can predict treatment efficacy with sufficient accuracy. Multiple markers may be combined to more accurately pinpoint patients who will respond favorably to immune checkpoint blockade medication. In this review, we have examined the breast cancer treatments, developments in research on the role of tumor markers in maximizing the clinical efficacy of immune checkpoint inhibitors, prospects for the identification of novel therapeutic targets, and the creation of individualized treatment plans. We also discuss how tumor markers can provide guidance for clinical practice.

Molecular subtypes predict the preferential site of distant metastasis in advanced breast cancer: a nationwide retrospective study.

Objective: This study aimed to explore possible associations between molecular subtypes and site of distant metastasis in advanced breast cancer (ABC). Methods: 3577 ABC patients were selected from 21 hospitals of seven geographic regions in China from 2012-2014. A questionnaire was designed to collect medical information regarding demographic characteristics, risk factors, molecular subtype, recurrence/metastasis information, and disease-free survival (DFS). The cancers were classified into Luminal A, Luminal B, HER2-enriched and Triple Negative subtypes. Chi-square test and multivariate Cox proportional hazard models were performed to explore the associations between molecular subtypes and distant metastasis sites. Results: A total of 2393 cases with molecular subtypes information were finally examined. Patients with Luminal A (51.1%) and Luminal B (44.7%) were most prone to bone metastasis, whereas liver metastasis was more frequently observed in HER2-enriched ABC patients (29.1%).The cumulative recurrence and metastasis rates of ABC patients at 36 months of DFS were the most significant within molecular types, of which Triple Negative was the highest (82.7%), while that of Luminal A was the lowest (58.4%). In the adjusted Cox regression analysis, Luminal B, HER2-enriched and Triple Negative subtypes increased the risk of visceral metastasis by 23%, 46% and 87% respectively. In addition, Triple Negative patients had a higher probability of brain metastasis (HR 3.07, 95% CI: 1.04-9.07). Conclusion: Molecular subtypes can predict the preferential sites of distant metastasis, emphasizing that these associations were of great help in choices for surveillance, developing appropriate screening and cancer management strategies for follow-up and personalized therapy in ABC patients.

Adverse reactions and efficacy of camrelizumab in patients with lung adenocarcinoma with high PD-L1 expression: A case report.

RATIONALE: Immune checkpoint inhibitors have been rapidly developed for lung cancer therapy and major clinical guidelines have recommended them as the optimal first-line treatment for PD-L1-positive advanced lung cancer. Unfortunately, there is a lack of efficient prediction tools for the occurrence of immune-related adverse events (irAEs) caused by immunotherapy, and there is a lack of real-world data on the processing of irAEs, particularly those occurring in multiple systems simultaneously. PATIENT CONCERNS: We report a 62-year-old male with expectoration who was diagnosed with lung adenocarcinoma with brain and bone metastases. DIAGNOSES: The results of the lung cancer tissue biopsy showed lung adenocarcinoma. Gene detection results of lung cancer tissue biopsy showed that the KRAS gene G12D was mutated and PD-L1 was positive, with a tumor proportion score of 95% (Dako 22C3 IHC platform). INTERVENTIONS: The patient initially received 1 cycle of pemetrexed in combination with cisplatin-based chemotherapy. After the results of PD-L1 testing were reported, he received 1 cycle of camrelizumab immunotherapy in combination with pemetrexed plus cisplatin based chemotherapy. OUTCOMES: Seventeen days after treatment, the patient presented with symptoms such as yellow staining of the sclera and skin, itching throughout the body, dry mouth, and ecchymosis of the skin of the right lower extremity, which continued to worsen. Following treatment with 2 mg/kg methylprednisolone, the patient's condition continued to deteriorate. IrAEs were controlled after dose escalation to 8 mg/kg in combination with plasma exchange therapy and treatment with multiple doses of mycophenolate ester. The patient then received no treatment for almost 2 months, but examination revealed that the tumor still had a persistent shrinkage reaction. LESSONS: Camrelizumab has been well tolerated in several studies, but in patients with high PD-L1 expression and a G12D mutation in KRAS, one should be alert to the development of serious or even multisystem immune-related adverse effects. Timely and individualized selection of the hormone dosage is essential for the treatment of immunotherapy-induced multisystem irAEs.

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.

Watson for oncology decision system for treatment consistency study in breast cancer.

The Watson for Oncology (WFO) decision system has been rolled out in many cancers. However, the consistency of treatment for breast cancer is still unclear in relatively economically disadvantaged areas. Patients with postoperative adjuvant stage (January 2017 to December 2017) and advanced-stage breast cancer (January 2014 to December 2018) in northwest of China were included in this study. Patient information was imported to make treatment decisions using Watson version 19.20 analysis and subsequently compared with clinician decisions and analyzed for influencing factors. A total of 263 patients with postoperative adjuvant breast cancer and 200 with advanced breast cancer were included in this study. The overall treatment modality for WFO was in 80.2% and 50.5% agreement with clinicians in the adjuvant and advanced-stage population, respectively. In adjuvant treatment after breast cancer surgery, menopausal status (odds ratio (OR) = 2.89, P = 0.012, 95% CI, 1.260-6.630), histological grade (OR = 0.22, P = 0.019, 95% CI, 0.061-0.781) and tumor stage (OR = 0.22, P = 0.042, 95% CI, 0.050-0.943) were independent factors affecting the concordance between the two stages. In the first-line treatment of advanced breast cancer, hormone receptor status was a factor influencing the consistency of treatment (χ2 = 14.728, P < 0.001). There was good agreement between the WFOs and clinicians' treatment decisions in postoperative adjuvant breast cancer, but poor agreement was observed in patients with advanced breast cancer.

Survival nomogram for patients with de novo metastatic breast cancer based on the SEER database and an external validation cohort.

Background: On average, 5-10% of patients are diagnosed with metastatic breast cancer (MBC) at the initial diagnosis. This study aimed to develop a nomogram to predict the overall survival (OS) in these patients. Methods: The nomogram was based on a retrospective study of 9435 patients with de novo MBC from the Surveillance, Epidemiology, and End Results (SEER) database. The predictive accuracy and discriminative ability of the nomogram were determined using the concordance index (C-index), area under the time-dependent receiver operating characteristic curve (AUC), and calibration curve. Decision curve analysis (DCA) was employed to evaluate the benefits and advantages of our new predicting model over the 8th edition of the American Joint Committee on Cancer (AJCC) Tumor Node Metastasis (TNM) staging system. The results were validated in a retrospective study of 103 patients with de novo MBC from January 2013 to June 2022 at an institution in northwest China. Results: Multivariate analysis of the primary cohort revealed that independent factors for survival were age at diagnosis, pathological type, histological grade, T stage, N stage, molecular subtype, bone metastasis, brain metastasis, liver metastasis, lung metastasis, surgery, chemotherapy, and radiotherapy. The nomogram achieved a C-index of 0.688 (95% confidence interval [CI], 0.682-0.694) in the training cohort and 0.875 (95% CI, 0.816-0.934) in the validation cohort. The AUC of the nomograms indicated good specificity and sensitivity in the training and validation cohorts, respectively. Calibration curves showed favorable consistency between the predicted and actual survival probabilities. Additionally, the DCA curve produced higher net gains than by the AJCC-TNM staging system. Finally, risk stratification can accurately identify groups of patients with de novo MBC at different risk levels. Conclusions: The nomogram showed favorable predictive and discriminative abilities for OS in patients with de novo MBC. Other populations from different countries or prospective studies are needed to further validate the nomogram.