Integrating acellular scaffolds with cell-laden hydrogels holds great potential for engineering soft tissue constructs with structural integrity and uniform cellular distribution. However, achieving sustained and viable tissue regeneration remains a challenge due to poor nutrient diffusion and vascularization in bulk hydrogels. We propose to incorporate cell-laden microgels into polymeric scaffolds to engineer highly-permeable living constructs for vascularized adipose tissue regeneration. The cell-laden microgels, with the size ranging from 200 μm to 600 μm, are produced by electrospraying, coated with fibrin precursors, and embedded in a polymeric scaffold to form a mechanically robust construct with interconnected microporous structures. The microgels with a size of ∼200 μm exhibited better mass diffusion, improving viability and proliferation of encapsulated adipose tissue-derived stem cells compared with the bulk hydrogel. Human umbilical vein endothelial cells can be further introduced into the voids among the cell-laden microgels to form a pre-vascularized cellular network inside the assembled constructs. In vivo, the permeable living constructs can effectively maintain their original shape, significantly enhance tissue infiltration, promote vascularization, and alleviate hypoxia, thereby facilitating adipose tissue regeneration. The scaffold-assisted cell-laden microgel assembly strategy provides new insights into engineering living constructs with a structurally stable, permeable microenvironment for vascularized tissue regeneration. STATEMENT OF SIGNIFICANCE: This work reports a scaffold-assisted strategy for assembling ADSC-laden electrosprayed microgels within a 3D-printed polymeric scaffold to create a mechanically robust yet permeable living construct for vascularized adipose tissue regeneration. The inherent inter-microgel voids in the assembled living constructs facilitate mass diffusion, thereby enhancing cell viability and proliferation compared with those in bulk hydrogel. To create a pre-vascularized living construct, HUVECs are introduced into the voids among the cell-laden microgels, which form an endothelial network among the microgels and promote ADSC differentiation. Owing to their structural stability and high permeability, the engineered living constructs can maintain a designated regeneration volume upon in vivo implantation, with improved vessel and tissue ingrowth and reduced hypoxia, further enhancing adipogenesis.

BackgroundTriple-negative breast cancer (TNBC) is an aggressive subtype characterized by the absence of estrogen receptor, progesterone receptor, and HER2 expression, which limits the availability of targeted therapies and results in poor prognosis. Immune checkpoint blockade (ICB) therapies have emerged as promising treatments by enhancing anti-tumor immunity; however, a substantial proportion of patients with TNBC exhibit primary or acquired resistance. This resistance is largely influenced by the tumor microenvironment (TME). This study uses integrated single-cell and spatial transcriptomics to elucidate key cellular mechanisms of resistance, with particular emphasis on lipid-mediated stromal-immune interactions within the TNBC TME.MethodsThis investigation encompassed analysis of single-cell RNA sequencing (scRNA-seq) data from three TNBC datasets and spatial transcriptomic data from 43 TNBC samples. Spatial niches and cell-cell interactions were identified using the Multimodal Intersection Analysis (MIA) algorithm. Experimentally, adipose-derived mesenchymal stem cells (AD-SCs) were co-cultured with MDA-MB-231 TNBC cells to generate lipid-processing CAFs (lpCAFs) and subsequently co-cultured with THP-1 macrophages. Lipid metabolism and M2 polarization of macrophages were assessed using BODIPY staining, Oil Red O, qPCR, flow cytometry and Western blotting techniques.ResultsABCA8+ lpCAFs and APOE+ lipid-associated macrophages (LAMs) exhibited significant enrichment in ICB-resistant TNBC, with co-localization at the immune-stromal junction. lpCAFs facilitated M2 macrophage polarization through lipid metabolism reprogramming, establishing an immunosuppressive TME. High ABCA8 expression demonstrated correlation with enhanced M2 macrophage infiltration, decreased cytotoxic immune cells, and poorer prognosis. Experimental validation demonstrated that lpCAFs increased expression of lipid metabolism and M2 polarization marker in macrophages, substantiating their immunosuppressive function.ConclusionABCA8+ lpCAFs and APOE+ LAMs contribute to ICB resistance in TNBC through the establishment of an immunosuppressive TME via lipid metabolism reprogramming. Therapeutic intervention targeting the ABCA8-lipid axis presents a promising strategy to enhance ICB efficacy, potentially advancing TNBC treatment outcomes and improving patient survival.

Trastuzumab-based HER2-targeted therapy remains the cornerstone treatment for HER2-positive breast cancer. However, its clinical efficacy is significantly modulated by the tumor microenvironment (TME). Our single-cell sequencing analysis of clinical samples revealed that patients with poor radiologic response after trastuzumab-based neoadjuvant therapy presented significant enrichment of TIGIT+ NK cells with high immune checkpoint expression, exhausted CD8+ T cells, and immunosuppressive regulatory T cells (Tregs). Further analyses leveraging cell-cell communication, spatial transcriptomics, and multiplex immunofluorescence showed that SPP1+ tumor-associated macrophages (SPP1+ TAMs) enrichment was associated with dysfunctional NK- and T-cell states in tumors from patients with poor radiologic response. Functional validation studies revealed that SPP1+ TAMs actively induced exhaustion phenotypes in both NK cells and CD8+ T cells, thereby impairing trastuzumab-dependent antibody-dependent cellular cytotoxicity (ADCC) and adaptive immune responses. In vivo experiments using humanized NCG murine models further confirmed the SPP1+ TAMs-mediated suppression of NK cell function. Significantly, HER2-positive breast cancer patients with elevated SPP1⁺ TAMs levels experienced both reduced efficacy of trastuzumab neoadjuvant therapy and diminished long-term survival prospects. In summary, our findings provide the first systematic characterization of TME remodeling following trastuzumab therapy, identifying SPP1+ TAMs as a potential driver of trastuzumab resistance. This work advances our understanding of microenvironmental mechanisms underlying trastuzumab resistance and suggests new therapeutic strategies targeting TAM-mediated immunosuppression.

Breast cancer, a prevalent malignancy worldwide, necessitates the identification of novel prognostic markers and therapeutic targets. This study delved into the significance of genes related to anoikis in breast cancer, with the aim of enhancing our understanding of its pathogenesis and treatment strategies. Initially, we identified differentially expressed anoikis genes in breast cancer tissues compared to normal tissues, revealing a complex landscape of gene expression. Through unsupervised clustering based on these genes, we uncovered three distinct subtypes that exhibited unique prognostic outcomes. Subsequently, utilizing LASSO and Cox regression analyses, we developed a risk score model that accurately predicted patient survival in both discovery and validation cohorts. Furthermore, we explored the functional implications of these genes and discovered associations with immune cell infiltration as well as drug sensitivity. Our analysis on drug sensitivity revealed potential antineoplastic agents that could be tailored for specific subtypes of breast cancer. In conclusion, this comprehensive analysis provides novel insights into the role played by genes related to anoikis in breast cancer and holds promise for improved prognostic assessment and targeted therapy development.

BACKGROUND:The objective of this study was to provide an overview of the clinical outcomes associated with single-port endoscopic nipple/skin-sparing mastectomy with total prepectoral breast implant reconstruction. METHODS:From April of 2021 to April of 2024, patients undergoing single-port endoscopic nipple/skin-sparing mastectomy with total prepectoral breast implant reconstruction were selected to evaluate the efficacy and safety of this method and to collect information on patient-reported outcomes. RESULTS:A total of 218 patients were enrolled in this study, 207 of whom completed follow-up, yielding a follow-up rate of 95.0%. In terms of surgical safety, the occurrence of flap ischemic problems was 7.8%, and the occurrence of flap necrosis was 3.7%. The occurrence of nipple resection during surgery was 7.4%, and among the 191 patients who had their nipples preserved, the occurrence of nipple ischemia was 7.0%. The occurrence of nipple necrosis was 1.5%, that of infection 10.1%, and that of prosthesis removal 3.9%. Approximately 1.0% of patients experienced metastasis and recurrence during the median 14.3-month follow-up period, as demonstrated by the cumulative sum curve. A cumulative plot analysis indicated that it would require approximately 21 cases for the surgeon to achieve a meaningful reduction in operating time. CONCLUSIONS:Single-port endoscopic nipple/skin-sparing mastectomy with total prepectoral breast implant reconstruction is a safe, effective, and visually acceptable surgical technique. Although it provides good oncologic safety, further evidence is required to fully support its use. CLINICAL QUESTION/LEVEL OF EVIDENCE:Therapeutic, IV.

OBJECTIVE:To comprehensively assess the clinical efficacy, peri-procedure safety, and psychological impact of VAE for benign breast lesions. METHODS:This retrospective observational study included 1413 patients (2008 benign breast lesions) who underwent outpatient VAE between October 2020 and January 2025. Demographic data, lesion characteristics, histopathology, and procedure duration were extracted from electronic medical records (EMRs). Post-procedural complications, pre-/post-procedural anxiety levels (using SAS), and patient satisfaction were retrieved from clinician-documented follow-up records. RESULTS:Most patients (64.26 %) were aged 31-50 years, and all were female. Among 2008 excised lesions, solitary lesions occurred in 59.45 % of patients, with the upper outer quadrant being the most frequent location (44.42 %). Fibroadenoma was the most common diagnosis (78.14 %). High-risk lesions (sclerosing adenosis, papilloma, papillomatosis, and atypical hyperplasia) accounted for 3.04 %. Additionally, carcinoma in situ and invasive carcinoma were identified in 5 cases (0.25 %). The mean procedure duration was 23.33 ± 9.26 min, with low post-procedure complication rates (hemorrhage: 18.54 %, defined as incisional oozing soaking part of the innermost dressing, all resolving spontaneously without intervention; hematoma: 16.63 %, almost all managed with observation/warm compresses; infection: 0.57 %). Pain was reported by 81.32 % of patients post-procedurally, but only 7.57 % required oral analgesics and 0.36 % were not relieved by oral analgesics. 98.91 % achieved excellent cosmetic outcomes. Patient satisfaction was high (98.94 %). Pre-procedure anxiety scores decreased post-procedurally (mean score: 47.47 ± 8.20 vs. 43.27 ± 7.80, P < 0.001), with 72.03 % anxiety remission rate. CONCLUSION:VAE achieves excellent efficacy and safety with psychological benefits, supporting outpatient adoption. Long-term validation studies are warranted.

Triple-negative breast cancer (TNBC) is a subtype of breast cancer with strong invasiveness and poor prognosis, lacking effective therapeutic targets. Electrochemical sensors have significantly improved their detection sensitivity and specificity due to their advantages such as high sensitivity, high specificity, rapid response and portability. By using nanomaterials as electrode modification materials and designing specific biometric recognition components, their detection sensitivity and specificity have been greatly enhanced. In this study, electrochemical sensor technology was employed to detect the expression level of LINC00115 in TNBC cells. The corresponding biological models were constructed through cell culture and transfection experiments. The regulatory relationship between LINC00115 and its target genes was further analyzed through subcellular grading experiments, luciferase activity experiments and chromatin immunoprecipitation (ChIP) techniques. The interaction between LINC00115 and the miR-615-3p/TM9SF2 axis was further investigated through RNA pull down and RNA immunoprecipitation (RIP) experiments. All data were processed through statistical analysis tools. The results showed that the expression of LINC00115 in TNBC cells was significantly higher than that in normal mammary epithelial cells, and the high expression of LINC00115 was closely related to the proliferation, migration and invasion abilities of TNBC cells. The study revealed the expression of LINC00115 in TNBC and its mechanism of action through electrochemical sensor technology, indicating that LINC00115 upregulates the expression of TM9SF2 by targeting miR-615-3p, thereby promoting the proliferation and migration ability of TNBC cells.

Background: The current scarcity of appropriate breast fillers restricts the availability of breast-conserving surgery for breast cancer patients. Although breast reconstruction can be conducted following a mastectomy, the existing methods for reconstruction are constrained. Three-dimensional (3D) printing technique enables the production of patient-specific and custom-designed scaffold, which may solve this problem. Methods: A prospective, single-arm clinical trial was performed. This study enrolled breast cancer patients who were not suitable for traditional breast-conserving surgery, including primary tumors larger than 1.0 cm and less than 8.0 cm, or those presenting as multiple diffuse lesions limited to a single quadrant. 3D-printed scaffold was fabricated according to patient’s own magnetic resonance imaging (MRI) one week before surgery. Patients were assigned to receive the patient-specific 3D-printed scaffolds transplantation surgery. The primary endpoint of this study is to determine the safety and cosmetic outcomes of partial breast reconstruction using 3D-printed patient-specific scaffolds. The secondary endpoints include degradation of 3D-printed scaffold, complications and satisfaction of patients received this partial breast reconstruction surgery. Results: Between August of 2016 and August of 2023, 26 patients received partial breast reconstruction using 3D-printed patient-specific scaffolds. The median follow-up was 58.9 months (range, 29 to 88 months). Patients who received partial breast reconstruction with 3D-printed scaffolds have natural-looking and symmetrical breasts after surgery. One year after operation, mild depression at the implantation site was observed in four patients (15.4%). This number increased to seven (26.9%) after two years of surgery. No flap necrosis or ischemia was observed in the nipple and areola area in all patients. Hematoxylin & Eosin showed that fibrous connective tissue, fibroblast cells and blood vessels were observed inside/around the scaffold after one year of surgery. The average degradation rate of 3D-printed scaffolds is 54.07% at 12 months, 74.48% at 24 months, 86.94% at 36 months, 87.36% at 48 months, and 92.76% at 60 months. The breast satisfaction score rating by Breast-q scale is 68.5±15.7 at 6 months, 65.4±14.2 at 12 months, and 62.8±15.9 at 24 months. Conclusion: This is the first report of 3D-printed biodegradable scaffolds for breast reconstruction. Partial breast reconstruction using a 3D-printed scaffold presents a viable alternative for breast cancer patients who are not suitable candidates for conventional breast-conserving surgery, yielding promising outcomes. Citation Format: Lan Hou, Changjiao Yan, Mingkun Zhang, Liu Yang, Zhe Wang, Yuan Qin, Huan Zhang, Zijie Meng, Qing Yao, Rui Ling, Jiankang He, Juliang Zhang. A novel 3D-printed scaffold for patient-specific partial breast reconstruction: A Prospective, Single-Arm Clinical Trial [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2024; 2024 Dec 10-13; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(12 Suppl):Abstract nr P4-04-42.

Leaky and structurally abnormal blood vessels and increased pressure in the tumor interstitium reduce the infiltration of CAR-T cells in solid tumors, including triple-negative breast cancer (TNBC). Furthermore, high burden of tumor cells may cause reduction of infiltrating CAR-T cells and their functional exhaustion. In this study, various effector-to-target (E:T) ratio experiments are established to model the treatment using CAR-T cells in leukemia (high E:T ratio) and solid tumor (low E:T ratio). It is found that the antitumor immune response is decreased in solid tumors with low E:T ratio. Furthermore, single cell sequencing is performed to investigate the functional exhaustion at a low ratio. It is revealed that the inhibition of mitophagy-mediated mitochondrial dysfunction diminished the antitumor efficacy of CAR-T-cell therapy. The mitophagy agonist BC1618 is screened via AI-deep learning and cytokine detection, in vivo and in vitro studies revealed that BC1618 significantly strengthened the antitumor response of CAR-T cells via improving mitophagy. Here, injection hydrogels are engineered for the controlled co-delivery of CAR-T cells and BC1618 that improves the treatment of TNBC. Local delivery of hydrogels creates an inflammatory and mitophagy-enhanced microenvironment at the tumor site, which stimulates the CAR-T cells proliferation, provides antitumor ability persistently, and improves the effect of treatment.

To establish a prognostic stratification nomogram for non-metastatic male breast cancer to determine which patients can benefit from chemotherapy. A population-based study was conducted using data collected from the surveillance, epidemiology, and end results database. Cox proportional hazards analysis identified significant prognostic factors for survival. A prognostic stratification model was developed using R software. Propensity score matching was implemented to balance characteristics between the chemotherapy cohort and the non-chemotherapy cohort. The multivariate analyses indicated that age, race, grade, surgery, primary tumor, marital status, T stage, and N stage were independent prognostic factors for overall survival in non-metastatic metastatic MBC patients who did not receive chemotherapy (all P < 0.05). The C-index was 0.786 (95% CI 0.662-0.870) in the training cohort and 0.763 (95% CI 0.517-0.852) in the validation cohort. The nomogram effectively discriminated between low-risk, moderate-risk, and high-risk groups concerning OS (P < 0.0001). The current study developed the first prognostic stratification nomogram for non-metastatic MBC and identified that patients in the moderate-risk and high-risk groups are more likely to benefit from chemotherapy.

Three-dimensional (3D)-printed breast scaffolds have attracted increased attention for soft tissue reconstruction. However, the polymeric porous scaffolds commonly cause fibrous tissue ingrowth due to their limited immunomodulatory capabilities. In this study, we integrated polycaprolactone (PCL) scaffolds with adipose-derived mesenchymal stem cell (ADSC) exosome-laden Gelatin Methacrylate (GelMA) hydrogels (Exos@GelMA+PCL) to promote macrophage M2 polarization and adipose regeneration. The biohybrid scaffolds exhibited sustained Exo release, with a cumulative release of >80% by day 14. Internalized Exos enhanced RAW264.7 macrophage M2 polarizationin vitro, as confirmed by immunofluorescence and real-time quantitative PCR. Conditioned medium from scaffold-macrophage cocultures enhanced the proliferation, migration, and adipogenic differentiation of ADSCs.In vivo, Exos@GelMA+PCL biohybrid scaffolds significantly increased the proportion of M2 macrophages compared to controls (GelMA+PCL and PCL scaffolds). At 12 weeks, the biohybrid scaffolds achieved markedly higher adipose tissue area percentages (46.26 ± 4.55%) compared to GelMA+PCL scaffolds (23.76 ± 1.90%) and PCL scaffolds (26.14 ± 2.55%). This strategy offers an innovative immunomodulatory approach to enhance soft tissue regeneration in breast reconstruction by regulating the microenvironment.

BACKGROUND:Addition of anti-angiogenic inhibitors has the potential to enhance the efficacy of poly(ADP-ribose) polymerase (PARP) inhibitors; however, clinical evidence for their use in breast cancer is scarce. The FABULOUS study assessed fuzuloparib (an oral PARP inhibitor) with or without apatinib (an oral angiogenesis inhibitor) for breast cancer. METHODS:FABULOUS was an open-label, randomised, phase 3 trial done at 40 sites in China. Eligible patients were women aged 18-75 years, with HER2-negative metastatic breast cancer with deleterious or suspected deleterious germline BRCA1 or BRCA2 (BRCA1/2) mutations and an Eastern Cooperative Oncology Group performance status of 0 or 1. Patients were randomly assigned (1:1:1) to receive oral fuzuloparib 100 mg twice daily plus oral apatinib 500 mg once daily, oral fuzuloparib 150 mg twice daily, or chemotherapy of the physician's choice (either oral capecitabine 1000-1250 mg/m2 twice daily on days 1-14 of each 21-day cycle or intravenous vinorelbine 25-30 mg/m2 on days 1 and 8 of each 21-day cycle). Randomisation was done via a centralised interactive web-response system using block randomisation (block size of six), stratified by the number of previous chemotherapy regimens for metastatic disease, hormone receptor status, and previous use of platinum-based therapy. The primary endpoint was progression-free survival per blinded independent central review (BICR). Herein, we reported the findings of prespecified interim analysis. Efficacy was assessed in the intention-to-treat population. Safety was analysed in patients who received at least one dose of study medication. This study is registered with ClinicalTrials.gov (NCT04296370). Recruitment and follow-up are ongoing to achieve the target sample size and obtain long-term efficacy and safety data. FINDINGS:Between Oct 12, 2020, and Dec 13, 2023, 203 eligible patients were enrolled and assigned to receive fuzuloparib-apatinib (n=70), fuzuloparib (n=67), or chemotherapy (n=66). 191 (94%) patients were Han Chinese, and 12 (6%) were other ethnicity Chinese. At the present interim analysis, median time from randomisation to cutoff date was 24·2 months (IQR 13·2-31·8). Median progression-free survival per BICR was 11·0 months (95% CI 8·4-13·1) with fuzuloparib-apatinib, 6·7 months (4·2-7·6) with fuzuloparib, and 3·0 months (1·6-5·3) with chemotherapy. Compared with chemotherapy, fuzuloparib-apatinib (HR 0·27 [95% CI 0·17-0·43]; one-sided p<0·0001) or fuzuloparib alone (0·49 [0·32-0·75]; p=0·0004]) groups had significantly longer progression-free survival. Additionally, the fuzuloparib-apatinib group had significantly longer progression-free survival than fuzuloparib (0·60 [0·40-0·91]; p=0·0079). The most common grade 3-4 treatment-related adverse events were decreased neutrophil count (nine [13%]) and hypertension (nine [13%]) in the fuzuloparib-apatinib group; anaemia (25 [37%]) and decreased neutrophil count (14 [21%]) in the fuzuloparib group; and decreased neutrophil count (14 [24%]) and decreased white blood cell count (11 [19%]) in the chemotherapy group. Serious treatment-related adverse events occurred in nine (13%), 12 (18%), and eight (14%) patients in the fuzuloparib-apatinib, fuzuloparib, and chemotherapy groups, respectively. There were no treatment-related deaths in the fuzuloparib-apatinib and chemotherapy groups, and one (1%) patient in the fuzuloparib group died due to a treatment-related adverse event (septic shock). INTERPRETATION:Fuzuloparib, either as monotherapy or in combination with apatinib, provided statistically significant improvements in progression-free survival compared with chemotherapy in patients with HER2-negative metastatic breast cancer with germline BRCA1/2 mutations, presenting as new treatment options. FUNDING:Jiangsu Hengrui Pharmaceuticals, Natural Science Foundation of China, National Key Research and Development Program of China, Guangdong Science and Technology Department, Science and Technology Program of Guangzhou, Bureau of Science and Technology of Guangzhou, and Program for Guangdong Introducing Innovative and Entrepreneurial Teams.

BACKGROUND:Tumor-infiltrating natural killer (NK) cells are pivotal in modulating tumor progression, either by promoting or inhibiting neoplastic development. Nevertheless, the implications of NK cells in breast carcinoma remain inadequately understood. This investigation aimed to delineate the impact of NK cells on both the prognosis and the immune infiltration landscape in breast cancer. METHODS:NK cell marker genes were identified using single-cell sequencing data from breast cancer available in the Gene Expression Omnibus (GEO) database. A prognostic model was constructed based on data from The Cancer Genome Atlas (TCGA) and subsequently validated with the GEO dataset. Disparities in immune cell infiltration between low-risk and high-risk cohorts, as stratified by the prognostic model, were examined. Additionally, genes differentially expressed between these cohorts were subjected to enrichment analysis. RESULTS:A total of 29 NK cell marker genes were identified through single-cell sequencing, and a prognostic model was subsequently developed using machine learning techniques based on the TCGA data. This model demonstrated robust predictive performance when applied to both TCGA and GEO datasets. Notably, a significant difference in immune infiltration was observed between the low-risk and high-risk groups. The findings were further validated through enrichment analysis. CONCLUSIONS:In summary, we constructed a prognostic signature characterized by strong predictive performance, which has elucidated the critical role of NK cells in the pathogenesis of breast cancer. Furthermore, this model offers a predictive index and identifies a novel therapeutic target for the advancement of immunotherapeutic strategies in the clinical management of breast cancer patients.

Trastuzumab serves as a cornerstone of first-line therapy for HER2-positive (HER2+) breast cancer; however, a significant challenge arises due to the emergence of resistance within approximately one year of commencement of treatment, particularly in advanced cases with metastatic disease where its efficacy is limited. Our investigation into the tumor tissue from HER2+ breast cancer patients, employing single-cell sequencing and bioinformatics analysis, has elucidated a crucial mechanism underlying the reduced responsiveness of tumors to trastuzumab: the diminished infiltration and activity of natural killer (NK) cells within the tumor microenvironment (TME). To counteract this impediment, we meticulously selected two potent immune-modulating peptides TKD and IP-10p, which are known to recruit and enhance the activity of NK cells. Through in vitro experiments, we substantiated that bolstering the tumor infiltration and activity of NK cells can lead to an enhanced antibody-dependent cell-mediated cytotoxicity (ADCC) effect, thereby amplifying the anti-tumor activity of trastuzumab. Building upon this foundational discovery, we further designed HER2-targeted pH-sensitive nanoliposomes to encapsulate TKD and IP-10p peptides. The novel designed nanoliposomes were strategically employed in conjunction with NK cell supplement therapy within a HER2+ breast cancer model undergoing trastuzumab treatment, yielding a striking anti-tumor response and indicating that the combination strategy effectively reinvigorated the anti-tumor immune response. In essence, this study not only underscores a critical link between the diminished ADCC effect mediated by trastuzumab and the development of resistance in HER2+ breast cancer but also demonstrates leveraging HER2-targeted nanoliposomes to deliver NK cell immunopotentiators can significantly enhance the functional activity of NK cells and their infiltration within the TME, culminating in improved antitumor efficacy of trastuzumab through the augmentation of the ADCC effect.

e12601 Background: Breast reconstruction surgery is on the rise and can significantly improve patients' quality of life, and single-port lumpectomy breast reconstruction surgery is becoming more widely used because of its minimally invasive nature, clear field of view, and aesthetics. However, patient-reported outcome studies of anterior versus posterior pectoralis muscle in this procedure are still scarce, and more evidence is needed to provide guidance to clinicians. Methods: Patients who underwent single-port laparoscopic breast reconstruction surgery at Xijing Hospital between March 2021 to December 2023 were included and divided into two groups according to the position of the prosthesis in the pectoral muscle. Patient safety was assessed for surgical safety and tumor safety. Patient Reported Outcome (PRO) was assessed using the BREAST-Q questionnaire. Results: General situation: This study was included in 58 patients with a single -hole laparoscopic breast reconstruction, and 48 patients were included in the post -pectoral muscle group. Tumor safety: 100% recurrence-free survival, 100% disease-free survival, and 100% overall survival in the follow-up patients; there was no significant difference between the anterior and posterior pectoral muscle groups in the single-port cavity. Surgical safety: there was no significant difference between the pre-pectoral and post-pectoral groups in terms of operative time, intraoperative bleeding, nipple areola complex ischemia, periosteal contracture. there were significant differences in postoperative infection, postoperative pain, and flap ischemia between the two groups, with the anterior pectoralis muscle group having a lower rate of postoperative infection, less pain, and a lower rate of flap ischemia. Patient-reported outcomes: The breast satisfaction of the breast reconstruction of the thoracic muscles under the laparoscopy, the higher social psychological health score, and the lower score in chest pain. Conclusions: In our research, the two groups of patients with single -hole laparoscopic breast reconstruction did not have a bad ending, and the single -hole laparoscopic pectoral muscle reconstruction had lower postoperative complications, and had better patient reporting ending Therefore, without considering the economic situation, we recommend the reconstruction of a single -hole laparoscopic pectoral muscles.

Objective:To investigate the effectiveness of endoscopic radical mastectomy for breast cancer combined with total pectoral muscle reconstruction with breast implants. Methods:The clinical data of 138 female patients with breast cancer who met the selection criteria between April 2019 and December 2023 were retrospectively analyzed. The mean age of the patients was 43.8 years (range, 27-61 years). The maximum diameter of the tumors ranged from 1.00 to 7.10 cm, with an average of 2.70 cm. Pathological examination showed that 108 cases were positive for both estrogen receptor and progesterone receptor, and 40 cases were positive for human epidermal growth factor receptor 2. All patients underwent endoscopic radical mastectomy for breast cancer combined with total pectoral muscle reconstruction with breast implants. The operation time, intraoperative blood loss, prosthesis size, and occurences of nipple-areola complex (NAC) ischemia, flap ischemia, infection, and capsular contracture were recorded. The Breast-Q2.0 score was used to evaluate breast aesthetics, patient satisfaction, and quality of life (including the social mental health score, breast satisfaction score, and chest pain score). Patients were divided into two groups based on the time of operation after the technique was implemented: group A (within 1 year, 25 cases) and group B (after 1 year, 113 cases). The above outcome indicators were compared between the two groups. Furthermore, based on the postoperative follow-up duration, patients were classified into a short-term group (follow-up time was less than 1 year) and a long-term group (follow-up time was more than 1 year). The baseline data and postoperative Breast-Q2.0 scores were compared between the two groups. Results:The average operation time was 120.76 minutes, the average intraoperative blood loss was 23.77 mL, and the average prosthesis size was 218.37 mL. Postoperative NAC ischemia occurred in 21 cases (15.22%), flap ischemia in 30 cases (21.74%), infection in 23 cases (16.67%), capsular contracture in 33 cases (23.91%), and prosthesis removal in 2 cases (1.45%). The operation time of group A was significantly longer than that of group B ( P<0.05), and there was no significant difference in intraoperative blood loss, prosthesis size, and related complications between the two groups ( P>0.05). All patients were followed up 3-48 months (mean, 20 months). There were 33 cases in the short-term group and 105 cases in the long-term group. There was no significant difference in baseline data such as age, body mass index, number of menopause cases, number of neoadjuvant chemotherapy cases, number of axillary lymph node dissection cases, breast cup size, degree of breast ptosis, and postoperative radiotherapy constituent ratio between the two groups ( P>0.05). At last follow-up, the breast satisfaction score in the patients' Breast-Q2.0 score ranged from 33 to 100, with an average of 60.9; the social mental health score ranged from 38 to 100, with an average of 71.3; the chest pain score ranged from 20 to 80, with an average of 47.3. The social mental health score of the long-term group was significantly higher than that of the short-term group ( P<0.05); there was no significant difference in breast satisfaction scores and chest pain scores between the two groups ( P>0.05). No patient died during the follow-up, and 2 patients relapsed at 649 days and 689 days postoperatively, respectively. The recurrence-free survival rate was 98.62%. Conclusion:Endoscopic radical mastectomy for breast cancer combined with total pectoral muscle reconstruction with breast implants has fewer complications and less damage, and the aesthetic effect of reconstructed breast is better.

Background: Lactylation is implicated in various aspects of tumor biology, but its relation to breast cancer remains poorly understood. This study aimed to explore the roles of the lactylation-related genes in breast cancer and its association with the tumor microenvironment. Methods: The expression and mutation patterns of lactylation-related genes were analyzed using the breast cancer data from The Cancer Genome Atlas (TCGA) database and GSE20685 datasets. Unsupervised clustering was used to identify two lactylation clusters. A lactylation-related gene signature was developed and validated using the training and validation cohorts. Immune cell infiltration and drug response were assessed. Results: We analyzed the mRNA expression, copy number variations, somatic mutations, and correlation networks of 22 lactylation-related genes in breast cancer tissues. We identified two distinct lactylation clusters with different survival outcomes and immune microenvironments. We further classified the patients into two gene subtypes based on lactylation clusters and identified a 7-gene signature for breast cancer survival prognosis. The prognostic score based on this signature demonstrated prognostic value and predicted the therapeutic response. Conclusion: Lactylation-related genes play a critical role in breast cancer by influencing tumor growth, immune microenvironment, and drug response. This lactylation-related gene signature may serve as a prognostic marker and a potential therapeutic target for breast cancer.

Neoadjuvant therapy can yield clinical benefits in early-stage breast cancer with indications. The indications, treatment regimens, and efficacy of neoadjuvant therapy have been investigated, which have contributed valuable clinical evidence.[1,2] The Chinese Society of Breast Surgery convened a panel of breast disease experts to review and discuss the literature on neoadjuvant therapy for breast cancer and evaluate relevant evidence by referring to the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) system. Taking into account China's specific circumstances, the society and participating experts developed the Clinical Practice Guidelines for Neoadjuvant Therapy for Early-stage Breast Cancer (Version 2022) to serve as a reference for breast surgeons in China. Level of Evidence and Recommendation Strength The grading system for the level of evidence was developed by referring to the GRADE system and the findings from clinical studies in China, as indicated in the guideline evaluation system [Supplementary Table 1, https://links.lww.com/CM9/B963]. The recommendation strength of these guidelines combines the GRADE system and the specific characteristics of clinical practice in China [Supplementary Tables 2 and 3, https://links.lww.com/CM9/B963]. Recommendations Qualifications of the neoadjuvant therapy team The expert panel recommends that a multidisciplinary team (MDT) fully participate in the development and adjustment of neoadjuvant therapy strategies.[3] An MDT team should include members from the imaging, pathology, breast surgery, oncology, gynecology, genetic counseling, psychology, and nursing departments. Indications for neoadjuvant therapy The expert panel concurs with the indications for neoadjuvant therapy for early-stage breast cancer patients recommended by the Chinese Society of Clinical Oncology (CSCO) guidelines for breast cancer diagnosis and treatment. They highly recommend the implementation of neoadjuvant therapy for patients with indications. The indications for neoadjuvant therapy (grade IA) include a large tumor size (>5 cm), axillary lymph node metastasis, human epidermal growth factor receptor-2 (HER2)-positive breast cancer, triple-negative breast cancer, and breast-conservation intentions, but a large tumor size and breast volume pose a challenge for conserving the breasts.[1] Neoadjuvant treatment regimen The expert panel recommends that the standard adjuvant therapy regimen for breast cancer should serve as a reference when formulating neoadjuvant therapy strategies (grade IA). During neoadjuvant therapy, the appropriate dosage and duration of treatment should be administered (grade IA). The use of immune checkpoint inhibitors platinum drugs, or poly ADP ribose polymerase (PARP) inhibitors should be individualized (grade IA).[4] Neoadjuvant therapy evaluation The expert panel recommends conducting thorough evaluations before administering neoadjuvant therapy in breast cancer patients. The functions of vital organs should be evaluated by imaging and hematological examinations (grade IA) before neoadjuvant therapy. Oncology evaluations should be performed before neoadjuvant therapy. A staged evaluation should be conducted following the American Joint Committee on Cancer (AJCC) (version 8), and distant metastasis should be excluded by computed tomography (CT), magnetic resonance imaging (MRI), positron emission tomography (PET)-CT, or radionuclide scans (grade IA).[5] The expert panel recommends conducting a description of the breast tumor and/or axillary lymph node diameter before treatment using ultrasound, X-ray, and dynamic enhanced MRI (grade IA). Localization and marking of lesions should be conducted using tattoo/tumor description/metal clip implantation before treatment (grade IA). Localization and marking of positive axillary lymph nodes should be conducted with metal clip implantation before treatment (grade IA). The expert panel recommends evaluating the efficacy of neoadjuvant therapy every two cycles, using the same imaging method as the one used at baseline, following the Response Evaluation Criteria in Solid Tumors (RECIST) (1.1) (grade IA). The expert panel strongly recommends performing core needle biopsy (CNB)/vacuum-assisted breast biopsy (VABB) to obtain a histopathological diagnosis of breast lesions/lymph nodes before neoadjuvant therapy (grade IA). Secondary CNB and pathological evaluation of lesions can be performed for efficacy evaluation (grade IIA). Pathological efficacy evaluations should be conducted using the Miller & Payne/residual tumor burden (RCB) grading system (grade IA). Surgery after neoadjuvant therapy The expert panel recommends conducting planned neoadjuvant therapy for ≥4 cycles (grade IA). The timing of surgery following neoadjuvant therapy should be individualized, taking into account efficacy, patient compliance, tumor staging, and molecular typing.[6] Surgery should be recommended following imaging evaluations of clinical complete response (cCR) to neoadjuvant therapy (grade IA). Furthermore, surgery must adhere to the principle of achieving R0 resection (grade IA). Systemic treatment after neoadjuvant therapy The expert panel recommends that optional systematic treatment following neoadjuvant therapy should be determined by tumor staging, treatment response, and molecular typing (grade IA).[7] Conflicts of interest None. Statement These guidelines serve as a reference for breast disease specialists in clinical practice. However, these guidelines should not be used as the foundation for medical evaluation, nor do they arbitrate in any medical disputes. The guidelines are not intended for patients or non-breast specialists. The Chinese Society of Breast Surgery bears no responsibility for any results resulting from the improper application of these guidelines but reserves the right to interpret and revise the guidelines.

Background and Objective:Non-puerperal mastitis (NPM) is a breast disease with poor clinical manifestations, which seriously affects women's health and quality of life. Due to the low incidence rate of the disease and the paucity of related research, there is much misdiagnosis and mis-management of periductal mastitis (PDM) and granulomatous lobular mastitis (GLM). Therefore, understanding the differences between PDM and GLM, in terms of etiology and clinical manifestations, is crucial for patient treatment and prognosis. At the same time, choosing different treatment methods may not achieve the best treatment effect, so the appropriate treatment method can often reduce the patient's pain and reduce the recurrence of the patient's disease.Methods:The PubMed database was searched for articles published from 1 January 1990 to 16 June 2022 using the following search terms: "non-puerperal mastitis", "periductal mastitis", "granulomatous lobular mastitis", "mammary duct ectasia", "idiopathic granulomatous mastitis", "plasma cell mastitis", and "identification". The key findings of the related literatures were analyzed and summarized.Key Content and Findings:We systematically described the key points in the differential diagnosis, treatment, and prognosis of PDM and GLM. The use of different animal models for research and novel drugs to treat the disease were also described in this paper.Conclusions:The key points in the differentiation of the two diseases are clearly explained, and the respective treatment options and prognosis are summarized.

Background:Breast cancer (BC) patients have a higher mortality rate after COVID-19 infection, but data on vaccination of BC patients and attitude towards COVID-19 vaccination and safety after vaccination are lacking. We wanted to understand the willingness and factors of BC survivors to receive a COVID-19 vaccine, and their adverse reactions. The purpose is to judge the safety of vaccination, and find strategies to promote vaccination in BC patients.Methods:Offline and online questionnaire surveys were provided in outpatient clinics and on an online follow-up platform, respectively, to collect information. Factors influencing vaccination willingness were analyzed by univariate and multivariate logistic regression. All statistical tests were performed bilaterally, and a P value <0.05 was considered statistically significant. Patients who have been vaccinated need to fill in questions about the impact on quality of life after vaccination, the type and frequency of vaccination, and side effects.Results:A total of 497 valid questionnaires were collected; 289 (58.1%) BC survivors were vaccinated with a COVID-19 vaccine, and 379 (76.26%) BC survivors had a fully or basically accepting attitude toward vaccination. Survivors over 70 years of age, educated only to high school level, and those receiving chemotherapy had significantly lower levels of acceptance of COVID-19 vaccines. Multivariate logistic regression analyses suggested that treatment status and cognitive attitude were independent factors influencing COVID-19 vaccination among BC survivors. The main reason for being vaccinated was "doctor recommendation" (57.26%). Unwillingness to receive a COVID-19 vaccine was mainly due to "the unknown safety of the vaccine in cancer patients" (67.80%). A total of 97.56% of the survivors believed that vaccination had no or almost no effect on their quality of life. Among the BC survivors, 18 (6.23%) had adverse reactions after vaccination. All adverse reactions were grade 1 or 2, and no adverse reactions of grade 3 or above were reported. The adverse reactions reported by 15 survivors (83.33%) markedly improved within 1 week.Conclusions:In terms of cognitive attitudes toward COVID-19 vaccines, elderly individuals and those with a lower education level were less receptive to vaccination. Therefore, attention to elderly survivors can help improve the vaccination rate.