Human epidermal growth factor receptor 2 (HER2)-positive breast cancer is an aggressive subtype. While trastuzumab plus pertuzumab significantly improves outcomes, cardiotoxicity remains a major limitation. Traditional Chinese Medicine (TCM) posits that Platycodon grandiflorus A. DC. (PG) may offer cardioprotection by addressing “Qi deficiency” and “blood stasis”. This study aims to investigate the efficacy and safety of PG granules (PGG) in preventing anti-HER2 therapy-associated cardiotoxicity. In this double-blind, randomized, placebo-controlled trial, approximately 120 patients with HER2-positive early breast cancer initiating trastuzumab and pertuzumab will be randomly assigned (1:1) to receive either PGG or placebo granules for 18 weeks (6 cycles of 3 weeks). The primary outcome is left ventricular ejection fraction (LVEF) measured within 3 days after completing anti-HER2 therapy. Secondary outcomes include: (1) incidence of cardiotoxicity (LVEF decline to < 55

Abstract Background Targeting the neuro-immune microenvironment to suppress triple-negative breast cancer (TNBC) represents a critical strategy in tumor immunotherapy. Methods A syngeneic 4T1 orthotopic TNBC model in Balb/c mice was employed. EA was applied at ST36 (Zusanli) using systematically optimized parameters (2/15 Hz, 3 mA, 30 min, every other day). Multi-dimensional immunophenotyping by flow cytometry, immunofluorescence, and Western blot was performed across tumor, blood, and splenic compartments. Transcriptome sequencing coupled with KEGG/GSEA pathway analysis was used to identify downstream signaling networks. The NGF/Hippo/YAP axis and adrenergic receptor subtype specificity were validated through pharmacological intervention in vitro, while EA synergy with αPD-L1 was assessed in a CD8 + T cell-depletion model. Results ST36 stimulation at 3 mA preferentially suppressed TNBC tumor growth and augmented intratumoral immune infiltration, characterized by elevated CD8 + T cells, NK cells, and M1-polarized macrophages. EA significantly enhanced CD8 + T cell effector capacity, upregulating perforin, granzyme B, CD69, and ZAP70 phosphorylation, and synergized with αPD-L1 in a CD8 + T cell-dependent manner. Mechanistically, EA activated c-Fos + /ChAT + cholinergic neurons in the dorsal motor nucleus of the vagus (DMV) and reduced norepinephrine (NE) output in both circulation and tumors. Transcriptomic profiling identified NGF downregulation and Hippo pathway activation as central events. EA upregulated AMOT, driving YAP phosphorylation at Ser127, cytoplasmic sequestration of YAP, and suppression of downstream IL-6 secretion. In vitro, exogenous NGF suppressed YAP phosphorylation and promoted TNBC malignant behavior, effects fully reversed by the YAP inhibitor verteporfin. α2-adrenergic receptor (α2-AR) antagonism with yohimbine abrogated NE-induced NGF upregulation, pinpointing α2-AR as the receptor subtype linking sympathetic signaling to the NGF/Hippo axis. Conclusion EA at ST36 recalibrates neuro-sympathetic tone in TNBC by activating vagal cholinergic outflow, reducing NE-driven α2-AR/NGF/Hippo signaling, and thereby relieving immunosuppression while amplifying CD8 + T cell-mediated cytotoxicity. These findings establish a neuro-immune mechanistic framework for EA-based adjuvant immunotherapy in TNBC.

Background:Chemotherapy-related cognitive impairment (CRCI) affects up to 75% of breast cancer patients during treatment, with 35% experiencing persistent post-treatment deficits. Current interventions show limited efficacy, creating urgent need for targeted therapies. Ginkgo Ketone Ester (GBE), containing neuroprotective flavonoids and terpene lactones, represents a potential therapeutic strategy. Methods:This 24-week prospective cohort study enrolled 96 breast cancer patients (stage I-III) receiving anthracycline-based chemotherapy. Participants were allocated to GBE intervention (n = 48) or standard care (n = 48) groups. The GBE cohort received tablets containing 14.08-21.12 mg total flavonoids, ≥9.6 mg flavonol glycosides, and ≥2.4 mg terpene lactones (0.25 g, three times daily) for 12 weeks. Cognitive function was assessed using Memory and Executive Screening (MES), Auditory Verbal Learning Test-Huashan Version (AVLT-H), and Shape Trail Test A/B at baseline, week 12, and week 24. Serum biomarkers (glutathione [GSH], reactive oxygen species [ROS], tumor necrosis factor-alpha [TNF-α]) and quality of life measures were evaluated correspondingly. Results:GBE administration significantly improved cognitive performance compared to controls (P < 0.05). The intervention group demonstrated 23% higher MES scores (72.29 ± 9.09 vs. 64.42 ± 8.63 at week 24), 31% better AVLT-H performance, and maintained stable completion times. Biochemical analysis revealed substantial GSH elevation (56% increase) and ROS reduction (41% decrease) at week 24, while TNF-α remained unchanged. CRCI incidence was significantly lower in the GBE group (66.67% vs. 89.58%, P < 0.007). Treatment compliance reached 89% with no serious adverse events reported. Conclusion:GBE demonstrates significant promise as a neuroprotective intervention for CRCI management, with substantial improvements in cognitive function and oxidative stress biomarkers. The favorable efficacy profile, excellent safety record, and high compliance support GBE's potential as adjunctive CRCI therapy. While neuroinflammatory effects were limited, robust antioxidant restoration and cognitive enhancement warrant further investigation through large-scale randomized controlled trials to validate long-term efficacy and optimize clinical protocols. Clinical Trial Registration:https://www.chictr.org.cn, identifier ChiCTR2200065694.

The interaction between TF binding and DNA methylation is increasingly recognized as a key player in the regulation of gene expression. However, the role of this interaction in regulating ICAM1 expression in breast cancer has not been elucidated. CpG methylation in the ICAM1 promoter is negatively correlated with ICAM1 expression, and ICAM1 expression is significantly positively correlated with DNMT and TET3 expression in breast cancer. TF binding attenuates ICAM1 promoter CpG methylation and promotes ICAM1 transcription. DNA methylation regulation enhances ICAM1 expression in breast cancer by promoting the transcription of transcription factors. In terms of mechanisms, RELA and STATs recruit TET3 to prevent DNMT-mediated DNA methylation, thereby maintaining CpG island hypomethylation in the ICAM1 promoter. Therefore, TF occupancy limits DNA methylation and affects ICAM1 expression in breast cancer.

This case report presents the first occurrence of Pneumocystis jirovecii pneumonia in a patient with breast cancer during CDK4/6 inhibitor therapy. Abemaciclib serves as a first-line therapeutic option for hormone receptor-positive/human epidermal growth factor receptor 2-negative advanced breast cancer. However, there are no documented cases in the literature linking abemaciclib to Pneumocystis jirovecii pneumonia. Notably, although rare, abemaciclib-induced severe lymphopenia may predispose patients to potentially life-threatening opportunistic infections. Optimal patient management requires multidisciplinary collaboration and strict compliance with American Society of Clinical Oncology/European Society for Medical Oncology guidelines to optimize the balance between therapeutic efficacy and infection risk mitigation. Critical strategies include early intervention and proactive surveillance to mitigate morbidity and mortality in this high-risk cohort. Consequently, the present case advocates for serial monitoring of lymphocyte counts and CD4+ levels during abemaciclib treatment, with implementation of primary prophylaxis protocols for patients exhibiting elevated risk profiles.

Triple negative breast cancer (TNBC) is an aggressive and immunogenic subtype of breast cancer. The absence of biomarker has given immune checkpoint inhibitors (ICIs) a broad prospect in this type of breast cancer. The infiltration of regulatory T cells (Tregs) expressing transcription factor forkhead box P3 (Foxp3) in the tumor microenvironment (TME) is the key factor leading to ICIs resistance. Therefore, elimination of tumor antigen-specific Tregs may be an important aspect of improving ICIs efficacy. In this study, it based on the Gene Expression Omnibus and The Cancer Genome Atlas database, along with in vivo and in vitro experimental models, to verified that the high expression of integrin-linked kinase (ILK) in TNBC is the key differential factor leading to the high infiltration of Foxp3+-Tregs in the TME. Then, we selected ILK-specific inhibitor, OSU-T315, to intervene in vitro and vivo. Importantly, we found that OSU-T315 blocked the secretion of CCL17/CCL22 in tumor cells by inhibiting the ILK/NF-κB pathway, resulting in the apoptosis of Foxp3+-Tregs and decreased programmed cell death-1 (PD-1) expression. Therefore, our findings indicate a novel mechanism of OSU-T315 with potential therapeutic application in TNBC.

Recently, immunotherapy has emerged as a promising and effective method for treating triple-negative breast cancer (TNBC). However, challenges still persist. Immunogenic cell death (ICD) is considered a prospective treatment and potential combinational treatment strategy as it induces an anti-tumor immune response by presenting the antigenic epitopes of dead cells. Nevertheless, the ICD process in TNBC and its impact on disease progression and the response to immunotherapy are not well understood. In this study, we observed dysregulation of the ICD process and verified the altered expression of prognostic ICD genes in TNBC through quantitative real-time polymerase chain reaction (qRT-PCR) analysis. To investigate the potential role of the ICD process in TNBC progression, we determined the ICD-dependent subtypes, and two were identified. Analysis of their distinct tumor immune microenvironment (TIME) and cancer hallmark features revealed that Cluster 1 and 2 corresponded to the immune “cold” and “hot” phenotypes, respectively. In addition, we constructed the prognostic signature ICD score of TNBC patients and demonstrated its clinical independence and generalizability. The ICD score could also serve as a potential biomarker for immune checkpoint blockade and may aid in the identification of targeted effective agents for individualized clinical strategies.

Exosomes, which are nanosized extracellular vesicles, have emerged as crucial mediators of the crosstalk between tumor cells and the immune system. Intercellular adhesion molecule 1 (ICAM1) plays a crucial role in multiple immune functions as well as in the occurrence, development and metastasis of cancer. As a glycoprotein expressed on the cell membrane, ICAM1 is secreted extracellularly on exosomes and regulates the immunosuppressive microenvironment. However, the role of exosomal ICAM1 in the immune microenvironment of breast cancer bone metastases remains unclear. This study aimed to elucidated the role of exosomal ICAM1 in facilitating CD8+ T cell exhaustion and subsequent bone metastasis in triple-negative breast cancer (TNBC). We demonstrated that TNBC cells release ICAM1-enriched exosomes, and the binding of ICAM1 to its receptor is necessary for the suppressive effect of CD8 T cell proliferation and function. This pivotal engagement not only inhibits CD8+ T cell proliferation and activation but also initiates the development of an immunosuppressive microenvironment that is conducive to TNBC tumor growth and bone metastasis. Moreover, ICAM1 blockade significantly impairs the ability of tumor exosomes to bind to CD8+ T cells, thereby inhibiting their immunosuppressive effects. The present study elucidates the complex interaction between primary tumors and the immune system that is mediated by exosomes and provides a foundation for the development of novel cancer immunotherapies that target ICAM1 with the aim of mitigating TNBC bone metastasis.

Background Breast cancer, particularly the Human epidermal growth factor receptor 2 (HER2) positive subtype, poses a significant health challenge for women worldwide. Trastuzumab plus Pertuzumab therapy has shown efficacy in treating HER2-positive breast cancer, but its use is limited by associated cardiotoxicity. Traditional Chinese Medicine (TCM) suggests that Platycodon grandiflorus A. DC. (PG) may have cardioprotective effects due to its ability to nourish qi and blood. This study aims to investigate the effective and safety of PG in preventing cardiotoxicity associated with anti-HER2 therapy. Method In this double-blinded, randomized, placebo-controlled trial, approximately 120 patients will be randomly assigned to either the PG or placebo groups, alongside undergoing 12 months of dual anti-HER2 therapies in a 1:1 ratio. Cardiotoxicity will be assessed at a median follow-up of 1 year. The primary outcome measure is left ventricular global longitudinal strain, with secondary outcomes including: (1) changes in left ventricular ejection fraction, (2) the occurrence of cardiotoxicity, (3) the occurrence of trastuzumab plus pertuzumab interruption, and (4) event free survival and overall survival rates among patients. Discussion This will be the first clinical study to determine whether PG can reduce the cardiotoxicity induced by trastuzumab plus pertuzumab treatment in HER2-positive early breast cancer patients. Trial registration Chinese Clinical Trial Registry (Registration Number ChiCTR2200061011)

During breast cancer development, programmed cell death 1 ligand 1 (PD-L1) overexpression in neutrophils leads to delayed apoptosis and promotes neutrophil hyperproliferation in the lung to form a premetastatic niche, which is beneficial for pulmonary metastasis. Platycodin D (PlaD), a triterpenoid saponin with known antiinflammatory and antitumor effects, has been reported to downregulate PD-L1 expression. This study aimed to investigate the inhibitory effect of PlaD on neutrophil PD-L1 in 4 T1 tumor-bearing mice and the potential mechanism of breast cancer pulmonary metastasis. In this study, the orthotopic 4 T1 murine mammary carcinoma model was administered 10 and 20 mg/kg PlaD by gavage. PlaD reduced the excess neutrophils and decreased their high migratory capacity in bone marrow, peripheral blood and lung tissue in the premetastatic period, thereby effectively inhibiting tumor growth and pulmonary metastasis. Moreover, PlaD inhibited the phosphatidylinositol-3-kinase (PI3K)/Akt pathway by decreasing the expression of PD-L1 in neutrophils and promoted neutrophil apoptosis. In vitro, PlaD treatment decreased the viability and inhibited migration of neutrophil-like dHL-60 in a dose-dependent manner. Similarly, PlaD inhibited the increase in PD-L1 induced by IFN-gamma stimulation and subsequently induced apoptosis in dHL-60 cells. In conclusion, the administration of PlaD inhibited the PI3K/Akt signaling pathway by reducing the expression of PD-L1 in neutrophils. PlaD promoted neutrophil apoptosis, thereby inhibiting the establishment of a premetastatic niche and ultimately blocking the development of pulmonary metastasis.

Sanyin formula (SYF) is used as a complementary treatment for triple-negative breast cancer (TNBC). The purpose of this study was to identify the potential functional components and clarify the underlying molecular mechanisms of SYF in TNBC. High-performance liquid chromatography–tandem mass spectrometry (HPLC-MS/MS) was used to identify the main components of SYF extracts. Network pharmacology and bioinformatic analyses were carried out to identify potential candidate targets of SYF in TNBC. Cell proliferation was determined with a Celigo imaging cytometer. Wound-healing and Transwell assays were adopted to evaluate cell migration. A Transwell cell-invasion assay was performed with Matrigel-coated membranes. In vivo bioluminescence imaging (BLI) and pathological analyses illustrated the effect of SYF on cancer cell metastasis in tumour-bearing mice. The inhibitory mechanism of SYF was investigated via quantitative PCR (qPCR) and Western blotting. We found that 3,4-dihydroxyphenyllactic acid, kaempferol, p-coumaric acid, and vanillic acid may be the active components of SYF. Molecular docking confirmed that kaempferol, p-coumaric acid, vanillic acid, and 3,4-dihydroxyphenyllactic acid bound stably to proteins such as AKR1C3, MMPs, and STAT3. SYF extract suppressed TNBC cell proliferation, migration, invasion, and metastasis by inhibiting JAK/STAT3 signalling and then regulating downstream genes, such as MMP-2/MMP-9. SYF regulates the expression of genes involved in cell proliferation, migration, and invasion by regulating the JAK/STAT3 signalling pathway and finally inhibits tumour cell metastasis in TNBC. The present study clarifies the mechanism by which SYF inhibits TNBC metastasis and lays an experimental foundation for the continued clinical development of SYF targeting the JAK/STAT3 pathway.

Breast hyperplasia is a benign disease with the highest incidence of breast diseases, mainly in young and middle-aged women. However, there are many treatment methods for this disease. Integrative Chinese and Western medicine have played a certain role in alleviating symptoms, but there is still lack of consensus on this. The Breast Diseases Professional Committee of World Federation of Chinese Medicine has unified the name of the disease and sorted out the diagnostic criteria of the disease. On the basis of traditional Chinese and Western medicine treatment, the time of surgical intervention was standardized,and the corresponding adjuvant treatment was recommended. This consensus adds subjective and objective efficacy evaluation criteria for the first time. Finally, after three rounds of expert voting, an expert consensus on the clinical diagnosis and treatment of breast hyperplasia with integrated traditional Chinese and Western medicine was formed.

Bone-related events caused by breast cancer bone metastasis substantially compromise the survival and quality of life of patients. Because triple-negative breast cancer (TNBC) lacks hormone receptors and Her2-targeted therapeutic options, progress in the treatment of TNBC bone metastasis has been very slow. Intercellular adhesion molecule 1 (ICAM1) is highly expressed in various cancers and plays an important role in tumorigenesis and metastasis. However, the effect and mechanism of ICAM1 in TNBC bone metastasis are still unknown. We found that ICAM1 was highly expressed in TNBC and correlated with prognosis in TNBC patients. Cell lines with high expression of ICAM1 exhibited enhanced bone metastasis in tumor-bearing mice, and silencing ICAM1 expression significantly inhibited bone metastasis in mice. ICAM1 interacted with integrins to activate the epithelial-to-mesenchymal transition program through TGF-β/SMAD signaling, ultimately enhancing cell invasiveness. Therefore, the findings of the present study provide a strong rationale for the application of ICAM1-targeted therapy in TNBC patients with bone metastasis.

目的 评价火针联合柴葵清消方治疗脓肿期热盛肉腐证非哺乳期乳腺炎的临床疗效.方法 将门诊纳入的脓肿期热盛肉腐证非哺乳期乳腺炎患者60例,采用区组随机、临床对照试验方法,按1:1分为试验组及对照组.每组30例,2组均内服柴葵清消方,试验组加用火针排脓引流法(简称火针疗法),对照组加用手术切开排脓引流法(简称切排疗法),疗程2个月.每2周测量脓腔及肿块面积,填写视觉模拟评分(VAS)疼痛量表.结果 试验组治疗6周时总有效率为86.7％(26/30),优于对照组[56.7％(17/30)],差异有统计学意义(x2=6.851,P＜0.05).与本组治疗前比较,两组治疗2、4、6、8周后脓腔面积和肿块面积逐渐减少,差异均有统计学意义(P＜0.05,P＜0.01);对照组治疗第8周与第6周比较,脓腔面积差异均无统计学意义(P＞0.05).与对照组同期比较,试验组治疗第2、4周时的脓腔面积及第4、6周肿块面积均减少,差异亦有统计学意义(P＜0.05,P＜0.01).试验组脓腔愈合平均时间为(57.67±16.78)d,优于对照组[(68.07±18.63)d],差异有统计学意义(t=-10.4,P＜0.05).治疗后2组患者VAS较治疗前均下降(t分别为-5.33、-5.46,P＜0.01),试验组明显优于对照组(t=-1.3,P＜0.01).Logistic多因素回归分析表明,初始乳房脓腔面积[OR=4.291,95％CI(1.124,21.479),P＜0.05]和肿块面积[OR=4.330,95％CI(1.185,23.106),P＜0.05]与疗效相关.优效性分析结果表明,初始脓腔面积＜20 cm2时,火针疗法优于切排疗法[RR=0.37,95％CI(0.01,0.81),P=0.03].结论 火针联合柴葵清消方治疗脓肿期热盛肉腐证非哺乳期乳腺炎可有效促进脓腔愈合,减轻患者痛苦.

Abstract Background Ruai-sanyin formula (RASYF) is composed of a variety of anticancer herbs. It is widely used in the treatment of triple negative breast cancer (TNBC) and has proved to inhibit tumor growth and lung metastasis in animal models, but there is no evidence for clinical application in the real world. Methods We conducted this prospective cohort study at 5 research centers in China from November 2016 to December 2018. RASYF was set as an exposure factor. TNBC patients within 3 months after completion of standard adjuvant treatment were included. The exposed group received RASYF treatment, while the non-exposed group received observation. The primary end point was disease-free survival (DFS). Secondary end points included, overall survival (OS), distant disease-free survival (DDFS), relapse-free survival (RFS), QLQ-BR23 assesses quality of life in patients and adverse events. Results A total of 613 eligible patients with operable TNBC were enrolled, of which 588 were included in the Full Protocol Set. At a median follow-up of 48 months, DFS time was longer in those assigned to RASYF compared with observation (3-year DFS, 89.6% vs. 83.5%, [HR = 0.61, 95%CI (0.39-0.95)]; P = 0.03). Similar outcomes were observed for RFS (3-year RFS, 92.1% vs. 85.9%, HR = 0.55, [95% CI, 0.34-0.91]; P = 0.02). However, there was no statistically significant difference in OS and DDFS between the groups. In exploratory subgroup analysis, RASYF benefits were greater in patients with age under the 40 (3-year DFS, 88.4% vs. 76.1%, [HR = 0.45, 95%CI (0.21-0.95)]; P = 0.03). And RASYF is helpful to the improvement of postoperative quality of life. Comparing to the observation group, RASYF increased the mean CFB of BR23 scores in body image (12.34 vs. 8.76, P = 0.03)，sexual function (11.79 vs. 9.23, P <0.01) , future perspective (9.90 vs. 6.53, P= 0.04), and decreased the scores of systemic therapy side effects (-12.41 vs. -9.24, P = 0.01). Safety analysis showed that RASYF caused major adverse reactions including impaired liver function (4.0%) and stomach pain (6.1%), but the overall security is controllable. Conclusion RASYF supplementation for 2 years after standard adjuvant chemoradiotherapy has certain clinical significance in preventing recurrence and metastasis and improving the quality of life of patients with early TNBC. Trial registration ClinicalTrials.gov: NCT03332368 Registered 6 November, 2017 (retrospectively registered)

Traditional Chinese tongue diagnosis plays an irreplaceable role in disease diagnosis. This study aimed to describe the tongue characteristics of patients with granulomatous lobular mastitis (GLM). Forty GLM patients and 40 non-GLM controls were evaluated using the Traditional Chinese Medicine subjective clinical interpretation and a TDA-1 Tongue Diagnostic and Analysis system. The associations between the image features of the tongue body and coating and the profiling of immune-inflammatory parameters were analyzed. GLM patients were prone to a reddish tongue bodies with thick, white, and greasy coatings. Thick and greasy tongue coating features are risk factors for GLM. GLM patients had higher levels of white blood cells (WBC), platelets, C-reactive protein, interleukin-2, and transforming growth factor-β (TGF-β) than non-GLM controls (P < .05). Also, tongue coating contrast and entropy values were significantly correlated with WBC or TGF-β levels in GLM patients (r < −0.310 andP < .05). We demonstrated that the hot evil and phlegm-dampness constitutions are the main characteristics of GLM. This might provide a reference for GLM diagnosis.

Abstract Background Xian-ling-lian-xia-fang (XLLXF), a Chinese medicine decoction, is widely used in the treatment of triple negative breast cancer (TNBC). However, the underlying mechanism of XLLXF in TNBC treatment has not been totally elucidated. Methods Here, network pharmacology and molecular docking were used to explore the mechanism of Traditional Chinese medicine in the treatment of TNBC. Then, biological experiments were integrated to verify the results of network pharmacology. Results Network pharmacology showed that the candidate active ingredients mainly included quercetin, kaempferol, stigmasterol, and β-sitosterol through the “XLLXF–active ingredients–targets” network. Vascular endothelial growth factor A (VEGFA) and matrix metalloproteinase (MMP) 2 were the potential therapeutic targets obtained through the protein–protein interaction (PPI) network. Molecular docking confirmed that quercetin, kaempferol, stigmasterol, and β-sitosterol could stably combine with VEGFA and MMP2. Experimental verification showed that XLLXF could inhibit proliferation, colony ability, and vasculogenic mimicry (VM) formation and promote cell apoptosis in TNBC. Laser confocal microscopy found that XLLXF impaired F-actin cytoskeleton organization and inhibited epithelial mesenchymal transition. Animal experiments also found that XLLXF could inhibit tumor growth and VM formation in TNBC xenograft model. Western blot analysis and immunohistochemical staining showed that XLLXF inhibited the protein expression of VEGFA, MMP2, MMP9, Vimentin, VE-cadherin, and Twist1 and increased that of E-cadherin, tissue inhibitors of metalloproteinase (TIMP)-1, and TIMP-3 in vitro and in vivo. Conclusions Integrating the analysis of network pharmacology and experimental validation revealed that XLLXF could inhibit VM formation via downregulating the VEGF/MMPs signaling pathway.

Background An elevated level of olfactomedin-like-2A (OLFML2A) is unfavorable for female breast cancer patients. Patients with a high mRNA level of OLFML2A receive a poor prognosis. Therefore, we speculate that inhibiting the expression of this gene may be beneficial to breast cancer patients. We previously found that silencing the OLFML2A gene by using mRNA interference significantly inhibited proliferation and migration in triple-negative breast cancer (TNBC) cells. Methods Cell activity and proliferation were determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and Celigo analyses. Cell migration and invasion were determined by wound-healing and transwell invasion assays. The mechanism of the inhibition of a small hairpin RNA that targets OLFML2A (shOLFML2A) was determined by using a GeneChip array, real-time quantitative PCR (RT-qPCR), and western blot analysis. Results Gene silencing by shOLFML2A induces apoptosis by promoting S phase arrest in TNBC cells. In addition, shOLFML2A decreased the progression of epithelial-mesenchymal transition (EMT). Additionally, microarray analysis showed that shOLFML2A significantly upregulated 428 genes and downregulated 712 genes. These significantly changed genes regulated DNA synthesis, chromosome alignment, microtubules and the cytoskeleton, cell movement, the cell cycle, cell necrosis, and apoptosis because they promoted G2/M DNA damage checkpoint regulation and p53 signaling, and because they inhibited integrin, hepatocyte growth factor (HGF), nerve growth Factor (NGF), and other tumor-promoting signaling pathways. Conclusions shOLFML2A reduces cell proliferation, migration, and invasion and promotes cell apoptosis. Therefore, the results of the present study suggest that OLFML2A is a potential therapeutic target for TNBC.

Purpose To evaluate the efficacy of the Sanyin formula (SYF) plus conventional standard chemotherapy in operable triple-negative breast cancer (TNBC) patients, a randomized controlled trial was implemented at 5 hospitals and cancer centers in China between May 23, 2016, and October 31, 2019. Materials and Methods Female patients aged 18 to 80 years with operable TNBC after definitive surgery were screened and enrolled. The exclusion criteria included metastatic disease, other tumors, or locally advanced disease. Patients were randomly divided into groups SYF plus conventional standard chemotherapy and placebo plus conventional standard chemotherapy at a ratio of 1:1. The primary endpoint of the investigation was disease-free survival (DFS), and secondary endpoints included overall survival (OS) and toxicity. Results A total of 252 operable female TNBC patients were randomized to receive SYF plus conventional standard chemotherapy (N = 127) or a placebo plus conventional standard chemotherapy (N = 125). At a median follow-up of 51 months, 5-year DFS time was longer in those assigned to SYF plus conventional standard chemotherapy compared with placebo plus conventional standard chemotherapy (94.2%vs 85.5%, hazard ratio [HR] = 0.40; 95%CI, 0.17-0.97; P = 0.034). The absolute benefit for 5-year DFS was 8.7% in the SYF plus conventional standard chemotherapy group. No statistically significant difference was observed in OS between the two groups (P = 0.23). Patients with negative node status benefited more from SYF plus conventional standard chemotherapy treatment (HR = 0.21, P-interaction = 0.013) in accordance with the exploratory subgroup analyses of DFS. Conclusions The results of the present study suggest that the traditional Chinese medicine SYF plus conventional chemotherapy regimens is an effective alternative adjuvant chemotherapy strategy for female operable TNBC patients. Clinical Trial Registration https://www.chictr.org.cn/searchproj.aspx, identifier ChiCTR-IPR-16008590.