Toripalimab, a novel PD-1 antibody, is approved for treatment of multiple solid tumors; however, its neoadjuvant use with chemotherapy for triple-negative breast cancer (TNBC) remains unevaluated. Additionally, induction chemotherapy followed by de-escalation of neoadjuvant immunotherapy remains underexplored. Therefore, we conducted a phase II trial investigating a novel neoadjuvant chemoimmunotherapy regimen including de-escalation of immunotherapy for early-stage TNBC. Chemotherapy and anti-PD-1 therapy were sequentially administered in a neoadjuvant setting to female patients with histologically confirmed stage II–III TNBC between June 9, 2020, and March 24, 2022. Patients received neoadjuvant therapy with four cycles of epirubicin-cyclophosphamide every 2 weeks, followed by toripalimab (240 mg) every 3 weeks plus nab-paclitaxel weekly for 12 weeks. The primary endpoint was total pathological complete response (tpCR; ypT0/is ypN0). Key secondary endpoints included breast pCR (bpCR; ypT0/is), event-free survival and biomarker analysis. Safety was also assessed. This study was registered with ClinicalTrials.gov (NCT04418154). Among 70 enrolled patients (median age, 51 years; 62.9% stage III), 66 completed treatment without progression and subsequently underwent surgery. The percentages of patients with a tpCR and bpCR were 39 of 70 (55.7%, 95% confidence interval [CI]: 43.3–67.6) and 41 of 70 (58.6%, 95% CI 46.2–70.2), respectively. Sixteen (22.9%) patients experienced grade ≥3 adverse events (AEs), frequently neutropenia (12, 17.1%) and leukopenia (11, 15.7%). The most common immune-related AE was hypothyroidism (5, 7.1%, all grade 1–2). Including 12 weeks of toripalimab in neoadjuvant chemotherapy conferred encouraging activity and manageable toxicity in patients with early TNBC, and this regimen warrants further investigation. 10.13039/501100001809 National Natural Science Foundation of China , Junshi Biosciences, and Jiangsu Hengrui Pharmaceuticals.

Background Despite the success of HER2-targeted therapy in achieving prolonged survival in approximately 50% of treated individuals, treatment resistance is still an important challenge for HER2+ breast cancer (BC) patients. The influence of both adaptive and innate immune responses on the therapeutic outcomes of HER2+BC patients has been extensively demonstrated. Methods Long non-coding RNAs expressed in non-pathological complete response (pCR) HER2 positive BC were screened and validated by RNA-seq. Survival analysis were made by Kaplan-Meier method. Cell death assay and proliferation assay were performed to confirm the phenotype of LINC00624. RT-qPCR and western blot were used to assay the IFN response. Xenograft mouse model were used for in vivo confirmation of anti-neu treatment resistance. RNA pull-down and immunoblot were used to confirm the interaction of ADAR1 and LINC00624. ADAR1 recombinant protein were purified from baculovirus expression system. B16-OVA cells were used to study antigen presentation both in vitro and in vivo. Flow cytometry was used to determine the tumor infiltrated immune cells of xenograft model. Antisense oligonucleotides (ASOs) were used for in vivo treatment. Results In this study, we found that LINC00624 blocked the antitumor effect of HER2- targeted therapy both in vitro and in vivo by inhibiting type I interferon (IFN) pathway activation. The double-stranded RNA-like structure of LINC00624 can bind and be edited by the adenosine (A) to inosine (I) RNA-editing enzyme adenosine deaminase RNA specific 1 (ADAR1), and this editing has been shown to release the growth inhibition and attenuate the innate immune response caused by the IFN response. Notably, LINC00624 promoted the stabilization of ADAR1 by inhibiting its ubiquitination-induced degradation triggered by β-TrCP. In contrast, LINC00624 inhibited major histocompatibility complex (MHC) class I antigen presentation and limited CD8+T cell infiltration in the cancer microenvironment, resulting in immune checkpoint blockade inhibition and anti-HER2 treatment resistance mediated through ADAR1. Conclusions In summary, these results suggest that LINC00624 is a cancer immunosuppressive lncRNA and targeting LINC00624 through ASOs in tumors expressing high levels of LINC00624 has great therapeutic potential in future clinical applications.

Background: Autologous breast reconstruction (ABR) significantly improves quality of life following mastectomy. However, ABR has traditionally been underutilized compared to implant‐based breast reconstruction (IBBR), partly due to its technical complexity, longer operative time, and relatively limited reimbursement. This study aimed to evaluate the patterns and evolving trends of ABR in China.Methods: Annual trends in breast reconstruction at Fudan University Shanghai Cancer Center (FUSCC) from 2000 to 2023 were retrospectively analyzed. Data included patient demographics, reconstruction timing, flap types, adjuvant radiotherapy status, and reoperations due to complications. Temporal trends were assessed using linear regression analysis.Results: Among 6,174 unilateral breast reconstruction cases, 2,123 (34.39%) involved ABR. Latissimus dorsi flaps (LDF) were the most commonly used technique overall (59.87%, n = 1,271), while the use of deep inferior epigastric perforator (DIEP) flaps increased markedly over time. By 2023, DIEP flaps accounted for 56.46% of all ABR procedures, becoming the predominant modality. Their rise was particularly notable in delayed and immediate‐delayed reconstructions, as well as in salvage ABR following implant failure. Among patients receiving adjuvant radiotherapy, the preference for DIEP flaps also increased significantly. Both LDF and DIEP flaps demonstrated low reoperation rates, highlighting their safety and clinical reliability.Conclusions: Autologous breast reconstruction in China is shifting toward increased utilization of DIEP flaps, particularly in delayed, immediate‐delayed, and implant‐salvage settings, as well as among patients undergoing radiotherapy. These findings support DIEP as a preferred flap type in modern reconstructive practice.

Endoscopy-assisted breast surgery is gaining popularity in the treatment of breast cancer owing to its minimally access nature. However, its application in Mainland China varies significantly across regions. We aimed to evaluate the current practices and challenges of endoscopy-assisted breast surgery in Mainland China using a nationwide cross-sectional survey. In 2022, we conducted a comprehensive questionnaire survey across Mainland China regarding the clinical practices of breast surgery in 215 hospitals, 198 responded fully before September 2024 and included for analysis. Data on hospital characteristics, types of EABS performed, agreements on indications and contraindications, complications, and surgeon preferences were collected and analyzed. Of 198 hospitals with complete responses in the endoscopy-assisted breast surgery section, 93 (47.0 %) could perform endoscopy-assisted breast surgery, and 7 (3.5 %) could perform robot-assisted breast surgeries. Hospitals performing endoscopy-assisted breast surgery had more developed breast surgery departments, higher numbers of inpatient beds, and a greater patient population. The median annual number of endoscopy-assisted breast surgery procedures per hospital was 55, with significant variability. Common procedures included endoscopy-assisted breast-conserving surgery and lumpectomy (15.5 % and 30.7 %, respectively). Breast reconstructions constituted 15.5 %. The most commonly reported complications were seroma formation and bleeding. Despite these complications, endoscopy-assisted breast surgery was considered safe and effective, with positive aesthetic and functional outcomes. To the best of our knowledge, this is the largest cross-sectional study on endoscopy-assisted breast surgery-related clinical practices in China, highlighting regional disparities and the need for standardized training and procedures.