Hong Liu

Inter‐tumor and intra‐tumor heterogeneity present significant challenges to achieving precise treatment in breast cancer (BC). To address this, we established a living biobank comprising 68 patient‐derived organoids (PDOs) from 50 patients across various regions, accurately maintaining the histological, genomic, and transcriptomic characteristics of the original tumors. Paired profiling demonstrated high concordance in mutation burden, copy number alterations, and molecular subtypes, capturing both inter‐ and intra‐tumor heterogeneity. Drug screening with four clinically used agents revealed pronounced response variability, enabling the development of multi‐gene expression signatures predictive of drug sensitivity. ACSL1 emerged as a key mediator of Doxorubicin resistance, enriched in malignant epithelial cells exhibiting focal adhesion/MAPK pathway activation and immune‐evasive features. Functional and mechanistic analyses identified focal adhesion kinase (FAK) as an upstream regulator of ACSL1, mediating resistance via ERK and STAT3 signaling. Inhibiting FAK or ACSL1 through pharmacological methods increased the sensitivity of resistant PDOs to Doxorubicin. The combined treatment was effective in decreasing tumor growth and preventing metastasis in xenograft models. Clinically, elevated ACSL1 expression correlated with advanced disease and poor survival. Collectively, these findings define BC heterogeneity, establish prognostic biomarkers, as well as uncover a means of Doxorubicin resistance that supports rational combination therapy.

Rosai-Dorfman Disease (RDD) is a rare form of sinus histiocytosis characterized by massive lymphadenopathy, commonly involving lymph nodes and occurring more frequently in children and young adults. Extranodal involvement of the breast is particularly uncommon. Here, we report a rare case of breast RDD, detailing the clinical findings, diagnostic process, and treatment, accompanied by a review of relevant literature. Given the limited cases of breast RDD reported, there is no established consensus on its diagnosis and treatment. This article aims to enhance understanding of breast RDD and inform clinical management practices.

This study aims to elucidate the technical points of double pedicled free deep inferior epigastric perforator (DIEP) breast reconstruction for breast cancer patients with large and ptotic breast. A retrospective analysis was conducted on patients who underwent DIEP flap breast reconstruction between January 2022 to December 2023, of which 92 immediate breast reconstructions using DIEP flap were included in this study. There were 21 cases underwent double-pedicled DIEP and 71 cases underwent unilateral pedicled DIEP. Using the internal thoracic vessels were employed for vascular anastomosis, and in the double pedicled DIEP group, 21 flaps survived while in the unilateral group 70 cases survived. The satisfaction degree of the double pedicled group was higher than that of the unilateral-pedicled group. In the double pedicled group, there was 0 case with moderate to severe radiation dermatitis, compared to 12 cases in the unilateral group. The double pedicled DIEP group tended to explore obviously higher biopsy rate (47.6%) of unexpected discovery internal mammary lymph nodes (IMLNs) than the unilateral pedicled group (16.9%). However, there was no significant difference (P=0.058) of the metastatic rate of IMLNs in the double pedicled group (50%) compared with that in the unilateral-pedicled group (25%). Clinically, for patients with large and sagging breasts, those requiring IMLN biopsy, those seeking to reduce side effects such as radiation-induced dermatitis, and those needing to ensure adequate blood supply to the flap, the double-tissue DIEP breast reconstruction surgery is an extremely effective autologous breast reconstruction method.

Objective: To evaluate the impact of primary tumor resection (PTR) on overall survival (OS) and cancer‐specific survival (CSS) in women with de novo bone‐only metastatic breast cancer (MBC). Methods: Women diagnosed with de novo bone‐only metastatic breast cancer between 2010 and 2017 were identified from the Surveillance, Epidemiology, and End Results (SEER) database. Patients were included if they had bone metastasis at diagnosis but no lung, liver, or brain involvement. Primary tumor resection was defined as any cancer‐directed breast surgery. Propensity scores were calculated using multivariable logistic regression incorporating demographics, tumor features, and treatment factors, followed by 1:1 nearest‐neighbor matching (caliper = 0.2 SD). Kaplan–Meier, Cox proportional hazards, and restricted mean survival time (RMST) analyses assessed overall survival (OS) and cancer‐specific survival (CSS). Time‐dependent ROC curves (timeROC) evaluated model discrimination. Determinants of PTR were examined using multivariable logistic regression. Results: A total of 3296 women with de novo bone‐only metastatic breast cancer were included (1252 with PTR; 2044 without). After 1:1 matching, 2002 well‐balanced patients remained (1001 per group). Median OS and CSS were significantly longer among patients undergoing surgery (OS: 69 vs. 39 months; CSS: 76 vs. 41 months; both p < 0.0001). PTR remained an independent predictor of improved OS (HR = 0.54, 95% CI 0.48–0.60, p < 0.001), with consistent benefit across subgroups. RMST differences (surgery − no surgery) increased with time, reaching 9.05 months for OS and 8.79 months for CSS at 60 months. Model discrimination was acceptable (AUCs for OS: 0.753, 0.734, 0.717 at 1–, 3–, and 5‐years). Radiation therapy was positively associated with PTR (OR = 1.37, 95% CI 1.12–1.68, p = 0.002), whereas well/moderate grade predicted lower odds (OR = 0.80, 95% CI 0.66–0.99, p = 0.036). Conclusions: In this large SEER‐based propensity‐matched analysis, primary tumor resection was associated with significantly improved overall and cancer‐specific survival among women with de novo bone‐only metastatic breast cancer. These findings suggest that selected patients with isolated bone metastasis may benefit from locoregional surgery, warranting further prospective validation.

Long non-coding RNAs (lncRNAs) have emerged as pivotal regulators in tumorigenesis and therapeutic resistance. This study investigates the prognostic significance and dual biological functions of lncRNA OTUD6B-AS1 in breast cancer (BC), focusing on its roles in immune evasion and ferroptosis resistance. Multi-omics data from The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), and lncRNA databases (AnnoLnc2, LncACTdb 3.0) were integrated to analyze OTUD6B-AS1 expression, clinical relevance, and molecular networks. Experimental validations included co-culture assays with CD8⁺ T cells, drug sensitivity tests, and ferroptosis marker analysis. OTUD6B-AS1 exhibited significant overexpression across multiple cancers, particularly in breast cancer (BC), where elevated levels strongly correlated with poor prognosis. Its expression was closely associated with key clinical indicators (T/N/M stage, ER/PR/HER2 status), prompting the development of a nomogram prognostic model with high clinical applicability. Genomic analysis revealed frequent amplification of OTUD6B-AS1 and co-occurrence of PIK3CA mutations. Co-expression and ceRNA networks highlighted its interaction with RNA degradation pathways. Notably, OTUD6B-AS1 was associated with immune evasion by regulating PD-L1 and CD8⁺ T cell activity. Concurrently, high OTUD6B-AS1 expression conferred ferroptosis resistance via GPX4/SLC7A11 modulation. In conclusion, OTUD6B-AS1 serves as a biomarker in BC, driving immune evasion and ferroptosis resistance. Targeting OTUD6B-AS1 may enhance immunotherapy efficacy and overcome chemoresistance, offering novel therapeutic avenues.

The clinical potency of anti-programmed death-ligand 1 (PD-L1) therapy in metastatic triple-negative breast cancer (TNBC) is modest primarily because of the intrinsic low immunogenicity and an immunosuppressive tumor microenvironment (TME). Photodynamic therapy (PDT), an inducer of immunogenic cell death (ICD), has the potential to enhance antitumor immune response and improve PD-L1 blockade efficacy. DTP, a novel photosensitizer developed previously, has demonstrated potent ROS-dependent photocytotoxicity, yet its immunomodulatory effects remain unexplored. This study investigated the induction of ICD and dendritic cell (DC) maturation following DTP-PDT in vivo and in vitro. A bilateral TNBC model was developed to assess the efficacy of DTP-PDT combined with α-PD-L1 therapy on untreated distant tumors and to explore its potential immunological mechanisms. The results showed that DTP-PDT effectively induced ICD, demonstrated by calreticulin membrane exposure, high mobility group box 1 protein release, and increased secretion of interferon-γ and tumor necrosis factor-α, resulting in DC maturation. The combination of DTP-PDT and α-PD-L1 significantly inhibited distant tumor growth. This effect was associated with increased CD8⁺ and CD4⁺ T cells infiltration, and reduced numbers of regulatory T cells, in the distant tumor and spleen. In conclusion, DTP-PDT enhanced TNBC sensitivity to α-PD-L1 by inducing ICD, and its combination withα-PD-L1 could remodel the immunosuppressive TME and enhance systemic immunity, resulting in a therapeutic effect against distant metastasis. This study provides experimental validation for a combined strategy of DTP-PDT and α-PD-L1, proposing a potential therapeutic approach for metastatic TNBC.

Background: Neoadjuvant therapy (NAT) is widely used in the treatment of breast cancer, and the pathological complete response (pCR) rate is increasing. However, currently, the prediction of pCR still lacks accuracy. This study aimed to investigate the accuracy of minimally invasive biopsy techniques in predicting breast pCR (bpCR) after NAT in breast cancer. Methods: From October 2022 to October 2024, a prospective single-arm study was conducted on 132 patients with primary breast cancer who achieved breast radiologic complete response (brCR) or breast radiologic partial response (brPR) after NAT at the Breast Center of Shandong Cancer Hospital. Before NAT, a marker clip was placed at the center of the tumor bed. After NAT, in patients with no residual lesions suggested by ultrasound, iodine-125 was placed under the guidance of mammography, followed by routine breast surgery (breast-conserving surgery or mastectomy). Postoperatively, multiple-site core needle biopsy (CNB) under ultrasound guidance was performed on the surgical specimen. The pathological results of CNB specimens were compared with those of surgical specimens to assess the accuracy of CNB in predicting bpCR (ypT0) after NAT. Results: A total of 52 patients (39.4%) achieved bpCR after NAT. Univariate analysis showed that tumor molecular subtypes, brCR after NAT, and axillary pathological complete response (apCR) were significantly associated with bpCR (P=0.02, 0.02, and P vs. 14.8%; PConclusions: The combination of imaging examinations and ultrasound-guided multiple-site CNB has the potential to accurately predict bpCR after NAT, making it possible to selectively avoid breast surgery in breast cancer patients after NAT.

Purpose To raise awareness of radiation recall dermatitis (RRD) in the context of radiotherapy combined with abemaciclib, and to explore its potential mechanisms, characteristics, and treatment options. Methods We conducted a case series study reporting the first instances of RRD induced by abemaciclib in two women with locally advanced luminal breast cancer. Both patients experienced skin reactions in previously irradiated areas following abemaciclib administration. Additionally, a comprehensive literature review was performed to analyze the potential mechanisms of RRD, characteristics of radiotherapy, triggering drugs, and available treatments. Results The case series demonstrated that abemaciclib can induce RRD in patients who have undergone radiotherapy. Both patients experienced significant skin reactions, which were successfully managed and resolved upon rechallenge with abemaciclib. The literature review highlighted the importance of recognizing RRD as a potential adverse effect of cyclin-dependent kinase 4/6 inhibitors (CDK4/6is), emphasizing the need for careful monitoring and appropriate management strategies. Conclusion Radiation recall dermatitis is a potential adverse effect of abemaciclib in patients receiving radiotherapy for breast cancer. Our findings underscore the importance of awareness and vigilance in managing patients on CDK4/6is.