1009 Background: The KEYNOTE-522 trial demonstrated that adding a PD-1 inhibitor to neoadjuvant chemotherapy significantly improves pathological complete response (pCR) rates, albeit with notable toxicity. The phase III Camrelief trial further confirmed that camrelizumab combined with sequential neoadjuvant chemotherapy significantly improved pCR compared with placebo in early-stage triple-negative breast cancer (TNBC). This study aimed to evaluate the efficacy and safety of camrelizumab plus neoadjuvant docetaxel and carboplatin in previously untreated stage II–III TNBC. Methods: This multicenter, randomized, open-label, phase III trial (ClinicalTrials.gov identifier: NCT05475678) enrolled eligible female patients aged 18-70 years with previously untreated stage II-III TNBC. Patients were randomized (2:1) to receive six 21-day cycles of docetaxel (75 mg/m²) and carboplatin (area under the curve=6) on day 1, with or without camrelizumab (200 mg intravenously on day 3). The primary endpoint was pCR (ypT0/Tis ypN0), assessed in the modified intention-to-treat (mITT) population, which included all patients who received at least one dose of the trial treatment. Results: Between December 2022 and June 2025, 369 patients from fourteen hospitals in China were enrolled and randomized to the camrelizumab-chemotherapy group (n=245) or the chemotherapy-alone group (n=124), of whom 352 comprised the mITT population. The pCR rate was 57.5% (134 of 233) in the camrelizumab-chemotherapy group versus 45.4% (54 of 119) in the chemotherapy-alone group (absolute difference, 12.2 percentage points; 95% CI, 1.4-22.9; one-sided P= 0.014). In the prespecified exploratory subgroup (CPS ≥1), pCR rates were 69.8% (97/139; 95% CI, 62.2%-77.4%) with camrelizumab-chemotherapy and 51.9% (41/79; 95% CI, 40.9%- 62.94%) with chemotherapy-alone (absolute difference, 17.9%; 95% CI, 5.3%-30.5%; one-sided P = 0.004). In the PD-L1-negative subgroup (CPS <1), pCR rates were 37.8% (31/82; 95% CI, 27.4%-48.2%) and 28.1% (9/32; 95% CI, 12.5%-43.7%), respectively (absolute difference, 9.7%; 95% CI, -10.5%-29.9%; one-sided P = 0.165). Grade 3 or higher treatment-related adverse events occurred in 24.8% (58/233) of patients in the camrelizumab-chemotherapy group, and 21.8% (26/119) in the chemotherapy-alone group. No treatment related deaths were reported. Conclusions: The addition of camrelizumab to neoadjuvant docetaxel and carboplatin significantly improved pCR rates in patients with stage II–III TNBC with a manageable safety profile. This anthracycline-free regimen represents a promising neoadjuvant treatment option for early TNBC. Clinical trial information: NCT05475678 .

The efficacy and safety of anti-HER2 therapy and immune checkpoint inhibitors combined with chemotherapy to treat HER2-positive advanced breast cancer that has failed standard HER2-directed therapies is unknown. This study evaluated the efficacy and safety of a novel, fully China-developed combination therapy—comprising inetetamab (an anti-HER2 monoclonal antibody), camrelizumab (an anti-PD-1 antibody), and utidelone (a microtubule inhibitor)—in this treatment-refractory population. The ICU study (NCT04681287) was a single-arm, multicentre, phase 2 trial conducted at five centres in China. Patients with HER2-positive MBC who had experienced progression on prior trastuzumab and TKIs were enrolled. The primary endpoint was the 3-month progression-free survival (PFS) rate in the per-protocol population. A total of 48 patients with a median of three previous systemic therapies for advanced disease (range, 1–4) were enrolled (median follow-up duration 43.0 months). The 3-month PFS rate in 46 patients was 71.67

BACKGROUND:The role of angiogenesis inhibitors in breast cancer (BC) remains unclear. Potential synergistic activity is observed between antiangiogenic tyrosine kinase inhibitors and cyclin-dependent kinase 4/6 inhibitors. This trial evaluated the feasibility of combining the angiogenesis-targeting tyrosine kinase inhibitor famitinib with the cyclin-dependent kinase 4/6 inhibitor dalpiciclib in patients with hormone receptor-positive human epidermal growth factor receptor 2-negative (HR+/HER2-) BC. METHODS:Patients with HR+/HER2- advanced BC were enrolled and treated with famitinib and dalpiciclib in combination with fulvestrant. A phase Ib dose-escalation study using a standard 3+3 design was conducted to determine the recommended phase II dose (RP2D). Phase II subsequently assessed the efficacy and safety of the RP2D. Exploratory biomarker analyses were performed to evaluate key gene mutations associated with this BC subtype, including PIK3CA and BRCA1/2. RESULTS:Based on dose-limiting toxicities and preliminary efficacy, daily famitinib 10 mg combined with dalpiciclib 100 mg plus fulvestrant was selected as the RP2D. An additional 28 patients were enrolled in phase II. The confirmed objective response rate (ORR) was 51.9% (95% confidence interval [CI]: 32.0%-71.3%), with a median progression-free survival (PFS) of 15.7 (95% CI: 7.3-25.4) months. The 2-year overall survival rate was 96.3% (95% CI: 76.5%-99.5%). Comparable ORRs and median PFS were observed regardless of PIK3CA or BRCA1/2 mutation status. Treatment-related adverse events of grade ≥3 were predominantly hematologic, including decreased neutrophil count (96.4%), decreased leukocyte count (75.0%), and decreased platelet count (10.7%). Patient enrollment was terminated after a comprehensive assessment of the benefit-risk profile of this regimen. CONCLUSIONS:Although the objective response threshold in the first stage of phase II was met, the median PFS did not demonstrate superiority over standard front-line regimens for HR+/HER2- advanced BC, and overlapping hematologic toxicities were observed. TRIAL REGISTRATION:ClinicalTrials.gov (NCT05176080) and Chictr.org.cn (ChiCTR2100053950).

Background: Accurate estimates of the global burden of young breast cancer are lacking. This study assesses its global burden and trends to inform control strategies. Methods: Using Global Burden of Disease (GBD) data (1990-2021) to assess YBC under 35 years in terms of age-standardized incidence rate (ASIR), prevalence rate (ASPR), mortality rate (ASMR), and DALY rate (ASDR). The study accounted for geographic variations and Socio-demographic index (SDI) quintiles, assessing trends and projecting rates to 2050 while examining risk factors. Primary outcomes were age-standardized rates and average annual percent change (AAPC). Results: In 2021, YBC accounted for substantial global disease burden, with 81,856 new cases (95% UI: 76,458-87,253), 687,819 prevalent cases (95% UI: 642,400-733,238), 18,597 deaths (95% UI: 17,191-20,003), and 1,178,721 DALYs (95% UI: 1,090,902-1,266,541). From 1990 to 2021, global ASIR (AAPC: 1.3%) and ASMR (AAPC: 0.3%) increased significantly, with projections indicating continued growth through 2050. While ASIR rose across all SDI quintiles, ASMR increased only in low and low-middle SDI quintiles (AAPC: 1.3% and 1.1%), but decreased in high and high-middle SDI quintiles (AAPC: 1.5% and-1.0%). Except for the lowest SDI quintile, YBC proportion within overall breast cancer burden decreased across other SDI quintiles. Dietary risks were the primary driver of YBC mortality, while high BMI showed an inverse association with mortality. Conclusion: YBC represents a growing global burden with significant disparities across SDI quintiles. Targeted interventions to address modifiable risk factors and improve healthcare access in less developed regions are essential to mitigate its impact.

Cancer therapy-induced thrombocytopenia (CTIT) is a common complication of anti-tumor therapy, leading to treatment delays or interruptions, increased bleeding risk and compromised outcomes. In the present study, we aimed to evaluate the efficacy and safety of hetrombopag, an oral thrombopoietin receptor agonist, for managing and preventing CTIT in patients with breast cancer. In this multi-center, randomized phase II clinical trial (NCT05394285), breast cancer patients with platelet counts < 50 × 10⁹/L during anti-tumor treatment (Cycle 1) were enrolled. Those patients were randomly assigned (1:1) to receive either hetrombopag or subcutaneous recombinant human thrombopoietin (rhTPO) until their platelet counts > 100 × 10⁹/L, which was defined as the thrombocytopenia treatment phase (TTP). During the secondary prevention phase (SPP), all cases as self-control received hetrombopag for 14 days starting on day 1 of the subsequent anti-tumor treatment cycle (Cycle 2). The primary endpoint was the response rate of the SPP. Secondary endpoints comprised the response rate of TTP (key secondary endpoint), other platelet-related parameters, and safety outcomes. Between September 2022 and May 2025, 67 patients with breast cancer were enrolled. After excluding one patient who withdrew informed consent, 66 patients were randomized. During the trial, 6 patients discontinued participation in the SPP, the remaining 60 patients constituted the per-protocol set (PPS). The majority of patients in the PPS (n = 47) received antibody-drug conjugates (ADCs) treatment. For the primary endpoint, the response rate was 85.0

Background:In recent years, immune checkpoint inhibitors (ICIs) have been widely used in the treatment of various malignant tumors, offering the possibility of long-term survival to some patients. However, ICIs can cause unique adverse events, which may even result in the discontinuation of treatment. Thus, reliable predictive biomarkers for immune-related adverse events (irAEs) need to be identified. This retrospective study aims to examine the correlation between nutritional status and serum biomarkers and the occurrence and severity of irAEs in lung cancer patients who had received ICIs. Methods:A total of 140 stage III/IV lung cancer patients who had received at least one dose of ICI therapy were included in the study. The clinical and pathological characteristics of the patients, such as body mass index (BMI), serum albumin (ALB), serum creatinine, prognostic nutritional index (PNI), monocyte-to-lymphocyte ratio (MLR), and platelet-to-lymphocyte ratio (PLR), were examined. Chi-squared tests were used to examine the relationships among the categorical variables. Logistic regression models were used to examine the effect of explanatory variables on binary outcomes. A survival analysis was performed using the Kaplan-Meier method and Cox model. Results:Of the 140 study patients, 66 (47.1%) experienced irAEs of any grade, and 15 (10.7%) experienced ≥ grade 3 (G3) irAEs. The patients with a low PLR (<135) showed a significantly higher incidence of irAEs than those with a high PLR (PLR ≥135) (P=0.007). Meanwhile, the patients with a baseline lymphocyte count ≥1.1×109/L had an increased incidence of irAEs (P=0.03). A significant association was observed between the PNI and the risk of ≥ G3 irAEs (P=0.02). The patients with baseline creatinine above 61.8 µmol/L exhibited different types of irAEs compared with those with baseline creatinine below 61.8 µmol/L. The results of the multivariate analyses showed that the PLR was an independent factor associated with the incidence of irAEs. Conclusions:The PLR may serve as a useful predictor of irAE incidence.

Background:The introduction of pertuzumab in mainland China in 2019 has significantly altered the treatment practice for early breast cancer; however, comprehensive real-world data on hormone receptor-positive (HR+) and human epidermal growth factor receptor 2-positive (HER2+) patients in this new era remain limited. Objective:To identify the clinicopathological characteristics, (neo)adjuvant treatment patterns, and clinical outcomes in treated patients with HR+/HER2+ early breast cancer in routine clinical practice in China. Design:A retrospective, observational study was conducted in patients with HR+/HER2+ early breast cancer who underwent surgery for breast cancer and had post-surgical pathologic reports available. De-identified patient data for this multicenter study were obtained from the National Cancer Information Database (NCID) in China. Methods:Patients were treated with neoadjuvant and adjuvant therapy with chemotherapy and/or HER2-targeted regimens in clinical practice. The main outcomes and measures were as follows: (neo)adjuvant treatment patterns, total pathologic complete responses (tpCR), breast pathologic complete responses (bpCR), disease-free survival (DFS), and event-free survival (EFS). Two-year DFS and EFS were evaluated using the Kaplan-Meier method. Multivariable logistic and Cox regression analyses were performed to identify associated factors of pCR and survival outcomes, respectively. The median duration of follow-up for the study was 13.9 months (range: 0.1-48.1). Results:A total of 13,323 patients with HR+/HER2+ early breast cancer were included in this analysis. Trastuzumab + pertuzumab (TP) was the most commonly used regimen in both neoadjuvant and adjuvant settings. Neoadjuvant therapy with dual HER2 blockade resulted in significantly higher tpCR rates (49.1% vs 29.9%) and bpCR rates (53.3% vs 34.4%) compared with trastuzumab alone (both p < 0.001), and numerically higher 2-year DFS rates (90.1% vs 87.1%; p = 0.273) and EFS rates (91.1% vs 89.4%; p = 0.297). Conclusion:The dual HER2 blockade regimens that were widely adopted in China for HR+/HER2+ early breast cancer have demonstrated effectiveness in improving pCR in routine clinical practice; a longer follow‑up is required to validate survival outcomes. Trial registration:None.

609 Background: Novel treatment options are needed to improve long-term outcome of high-risk early HR+/HER2− breast cancer. Evidence shows a programmed death 1 inhibitor combined with chemotherapy increases pCR rates in this subtype. We aimed to evaluate the efficacy and safety of serplulimab combined with nab-paclitaxel and epirubicin in high-risk, early HR+/HER2− breast cancer. Methods: This multicentre, single-arm, phase 2 trial was conducted in China at 6 hospitals. Patients were eligible if they were 18 years or older, with previously untreated early HR+/HER2- breast cancer, and Ki-67 greater than or equal to 20%, and had an Eastern Cooperative Oncology Group (ECOG) performance status of 0–1. Participants were allocated to intravenous nab-paclitaxel (260 mg/m 2 ) and intravenous epirubicin (75 mg/m 2 ) on the first day and intravenous serplulimab (4.5mg/kg) on the third day of the treatment cycle. 6 cycles of neoadjuvant treatment were administered. The primary outcome was pCR (defined as ypN0 or ypT0/is), assessed in the full analysis set, which included all patients who had started the trial treatment. We estimated that with enrollment of 109 participants, this trial would have 80% power to detect a true difference in the percentage of patients with a pCR of 10% at a one-sided alpha level of 0.025, with a dropout rate of 10%. This study is registered with ClinicalTrials.gov (NCT06394661). Results: Between Apr 28, 2024, and May 24, 2025, 136 patients were assessed for eligibility; 27 were ineligible and 109 participants were enrolled in this study, of whom 101 participants started trial treatment. Median age of the participants was 49 [range, 30 to 72] years at the time of enrolment, and 45 (44.6%) were PD-L1 positive (CPS ≥1). pCR was achieved in 23 patients (22.8%, 95%CI 15.3%-32.4%). PCR rate was numerically higher in patients with PD-L1 positive tumors (44.4%, 95%CI 30.0%-59.9%). During the neoadjuvant phase, 30 (29.7%) patients experienced grade 3 or higher treatment-related adverse events. The most common grade 3–4 adverse events were increased alanine aminotransferase (ALT; six [5.9%]), increased aspartate aminotransferase (AST; five [5.0%]), and diarrhea (four [4.0%]), There were no treatment-related deaths. Conclusions: Delayed serplulimab combined with nab-paclitaxel and epirubicin showed promising anti-tumour activity and manageable safety in patients with HR+/HER2− breast cancer; the pCR rate was higher in PD-L1 expression tumor. These findings support further evaluation of this regimen in randomized controlled trials. Clinical trial information: NCT06394661 .

As an anti-HER2 antibody-drug conjugate, SHR-A1811 has exhibited significant antitumor activity in patients with HER2-low advanced breast cancer. This trial aims to explore the efficacy and safety profile of SHR-A1811 as a neoadjuvant therapy for hormone receptor-positive, HER2-low (HR + /HER2-low) breast cancer. We conducted a single-arm, phase 2 study enrolling women aged 18 to 70 years with untreated HR + /HER2-low invasive breast cancer (cT2-3, cN0-3) and a Ki-67 proliferation index exceeding 14%. Eligible patients had an Eastern Cooperative Oncology Group performance status of 0 or 1, and received intravenous SHR-A1811 at a dose of 6.4 mg/kg every three weeks for eight cycles. The primary endpoint was the objective response rate, assessed in all patients who received at least one treatment cycle. Secondary endpoints included pathological complete response (pCR, residual cancer burden (RCB) 0–1 rate, event-free survival (EFS), disease-free survival (DFS), and distant disease-free survival (DDFS). In total, 66 of 101 screened patients (65.3%) were enrolled, with 65 included in the efficacy analysis and 66 in safety analysis. The objective response rate was 81·5% (95% confidence interval (CI), 70·0-90·1), exceeding the protocol-specified threshold of 66·0%. Pathological complete response (ypT0/Tis ypN0) was observed in 2 patients (3.1%; 95% CI, 0.4-10.8), while 6 patients (9.2%; 95% CI, 3.5-19.6) achieved a residual cancer burden class 0-1. Treatment-related grade ≥3 adverse events occurred in 37.9% of patients. The most common grade ≥3 adverse events were neutropenia (27.3%), leukopenia (16.7%), and anemia (13.6%). No treatment-related deaths or interstitial lung disease were reported. In summary, SHR-A1811 monotherapy achieved favorable response rates with manageable toxicity, suggesting a potential alternative neoadjuvant option for HR + /HER2-low breast cancer. Further randomized trials may be necessary to assess its clinical value more comprehensively. Follow-up continues for survival. ClinicalTrials.gov identifier: NCT05911958 Anti-HER2 antibody-drug conjugates (ADCs) have been approved for patients with Hormone Receptor positive (HR + ), HER2-low metastatic breast cancer. Here, the authors present a phase II interventional clinical trial evaluating the anti-HER2 ADC SHR-A1811 as neoadjuvant monotherapy in patients with HR + HER2-low breast cancer (HELEN-015).

Background Although HER2-targeted therapies have dramatically improved outcomes for patients with HER2-positive breast cancer, the immunosuppressive tumor microenvironment remains a major barrier to effective immunotherapy in this subtype. Therefore, we sought to develop a new bispecific antibody targeting both HER2 and C-type lectin domain family 5 member A (CLEC5A), a pattern recognition receptor on innate immune cells like macrophages, aiming to alter the tumor immune environment.Methods CLEC5A-HER2 bispecific antibodies were generated and evaluated for binding properties, macrophage activation, and phagocytic activity in vitro. Anti-tumor efficacy was assessed in multiple syngeneic mouse models, including orthotopic breast cancer models, with mechanistic studies and immune checkpoint inhibitor combinations.Results The CLEC5A-HER2 bispecific antibody was more effective in anti-tumor activity than either monotherapies or combinations of individual antibodies in various syngeneic models, including an orthotopic breast cancer model. Mechanistically, it converted "cold" tumors into "hot" tumors by promoting macrophage-mediated phagocytosis, repolarizing tumor-associated macrophages toward an M1-like phenotype, and enhancing antigen presentation and T-cell recruitment. This immune remodeling restored the CXCL9/10-CXCR3 axis, increased CD8+ T cell infiltration, reduced regulatory T cells, and underpinned a T cell-dependent anti-tumor response. Interestingly, combination therapy with CTLA-4 and PD-1 blockade exhibited strong synergistic effects without significant toxicity.Conclusions These results identify the CLEC5A-HER2 bispecific antibody as a potential immunotherapy for HER2-positive cancers by effectively engaging both innate and adaptive immunity.

Ginsenoside Rg1 (Rg1) has been reported to exert its adjunctive antitumor efficacy in cancer therapy, including hepatocellular carcinoma (HCC). Here, our study revealed the role of Rg1 on HCC involving ferroptosis. Functionally, Rg1 significantly inhibited the proliferation and migration ability of HCC cells, demonstrating its anti-HCC effect. In addition, Rg1 could induce the ferroptosis-related characteristics of HCC, thereby triggering ferroptosis. Mechanistically, SLC7A11 was identified as a potential downstream mediator of Rg1, and further studies are required to validate its functional role, and Rg1 inhibited the expression of SLC7A11. This downregulation of SLC7A11 by Rg1 recovered the ferroptosis sensitivity, thereby activating ferroptosis and contributing to HCC treatment. In conclusion, our findings unveil a link between Rg1 and ferroptosis, supporting a therapeutic strategy to overcome HCC by targeting ferroptosis.

1054 Background: Triple-positive breast cancer (TPBC; HR+/HER2+) represents a distinct subtype with suboptimal responses to conventional neoadjuvant chemotherapy combined with anti-HER2 therapy, with reported pCR rates of only 26%–43.8%, and is associated with significant treatment-related toxicities 1-3 . This highlights an urgent need for more effective and less toxic therapeutic strategies. We hypothesize that simultaneously targeting ER, HER2, and CDK4/6 pathways may enhance antitumor efficacy while enabling chemotherapy de-escalation. This phase II study investigates a response-guided, chemotherapy-free neoadjuvant regimen using dalpiciclib (a CDK4/6 inhibitor), aromatase inhibitor (AI), and dual HER2 blockade. Methods: This prospective, single-arm, two-stage Simon optimal design study planned to enroll 71 patients. In stage one, 20 patients were enrolled; proceeding to stage two required ≥6 pCRs. The final success threshold is ≥24 pCRs in 71 patients (α=0.05, power=80%, H0: pCR≤25% vs. H1: pCR≥40%). Eligible patients had stage II–IIIa HR+/HER2+ invasive breast cancer. Treatment included oral dalpiciclib (150 mg/day, 3 weeks on/1 week off), oral letrozole (2.5 mg/day; with ovarian suppression if premenopausal), and IV trastuzumab (loading 8 mg/kg, then 6 mg/kg) plus pertuzumab (loading 840 mg, then 420 mg) every 3 weeks. This was a response-adaptive design: after 2 cycles, MRI assessed tumor response. Patients achieving PR (≥30% reduction per RECIST 1.1) continued the same regimen for 6 cycles; non-responders switched to TCHP chemotherapy (docetaxel, carboplatin, trastuzumab, pertuzumab). The primary endpoint was pCR (ypT0/is ypN0) in the all-treated population. Secondary endpoints included ORR, RCB 0-1, EFS, and safety. Results: In the first stage, 20 patients were enrolled. Median age was 48 years (range 34–59). All were ER+ and HER2+ by central review. After 2 cycles, 15 of 20 patients (75%) achieved PR and continued on the dalpiciclib, letrozole, and dual HER2 blockade regimen. Of the 20 patients, 8 achieved pCR, with a rate of 40%. Among the MRI responders who continued the experimental arm, the pCR rate was 40% (6/15). Treatment was generally well-tolerated; the most common adverse events were neutropenia, leukopenia, anemia, and thrombocytopenia. No treatment-related discontinuations or cardiac toxicity of grade 3 or higher were observed. Conclusions: The first stage of this response-guided study met its predefined efficacy threshold (≥6 pCR in 20 patients). The neoadjuvant regimen combining dalpiciclib, an AI, and dual HER2 blockade shows promising pCR rates and a favorable safety profile in TPBC, supporting continued evaluation in the second stage of the trial. Clinical trial information: NCT06276868 .

509 Background: Docetaxel, carboplatin, trastuzumab, and pertuzumab (TCHP) is a standard neoadjuvant regimen for stage II–III human epidermal growth factor receptor 2 (HER2)–positive breast cancer; however, its use is associated with substantial treatment burden, particularly hematologic toxicity, highlighting the need for alternative strategies that maintain efficacy with different toxicity profiles.This study to determine whether a chemotherapy-de-escalated regimen of nanoparticle albumin–bound paclitaxel, trastuzumab, and the tyrosine kinase inhibitor pyrotinib (nab-PHPy) is noninferior to standard TCHP with respect to pathological complete response (pCR). Methods: The HELEN HER-013 trial was a multicenter, randomized, open-label, phase 3 noninferiority trial conducted at 15 centers in China. Women with previously untreated, operable stage II–III HER2-positive breast cancer were enrolled between May 2023 and May 2025.Participants were randomly assigned (1:1) to receive six 21-day cycles of either nab-paclitaxel, trastuzumab, and oral pyrotinib (nab-PHPy group) or TCHP group.The primary end point was pCR (ypT0/Tis ypN0), assessed in the modified intention-to-treat (mITT) population (patients who received ≥1 dose of study treatment). The prespecified noninferiority margin was −5.5%( ClinicalTrials.gov Identifier: NCT05918328 ). Results: Among 709 screened individuals, 610 were randomized, and 589 were included in the mITT population (295 in the nab-PHPy group and 294 in the TCHP group; all female). Median age was 51 years (interquartile range [IQR], 43–56) in the nab-PHPy group and 52 years (IQR, 45–57) in the TCHP group. The primary end point of pCR was achieved in 186 patients (63.1%; 95% CI, 57.4%–68.4%) in the nab-PHPy group and 174 patients (59.2%; 95% CI, 53.4%–64.8%) in the TCHP group. The between-group difference was 3.9% (95% CI, -4.2% to 11.9%), which met the prespecified criterion for noninferiority (noninferiority P = .01). Grade 3 or higher treatment-emergent adverse events occurred in 113 patients (38.3%) receiving nab-PHPy and 107 patients (36.4%) receiving TCHP. The most common grade 3 or higher adverse events were diarrhea (31.5% vs 17.0%), anemia (1.7% vs 10.2%), and nausea (0% vs 5.8%). No treatment-related deaths were reported. Conclusions: Among women with operable stage II–III HER2-positive breast cancer, neoadjuvant treatment with nab-PHPy was noninferior to TCHP with respect to pCR and was associated with a distinct toxicity profile, supporting its role as an alternative neoadjuvant strategy. Clinical trial information: NCT05918328 .

Methicillin-resistant Staphylococcus aureus (MRSA) remains a major global health threat with limited prophylactic options. Trained immunity, characterized by nonspecific functional reprogramming of innate immune cells, offers a promising strategy for infection control. Here, we identify paclitaxel (PTX), a microtubule-stabilizing agent widely used in cancer therapy, as a novel inducer of trained immunity in macrophages. Unlike the microtubule-destabilizing agent nocodazole (Noco), PTX enhanced macrophage proinflammatory responses, phagocytosis, and bacterial killing upon secondary stimulation. Mechanistically, PTX-induced training activated the stimulator of interferon genes protein (STING) pathway, evidenced by increased phosphorylation of STING, TBK1, and IRF3. STING deficiency abolished the trained immune responses and antimicrobial functions. PTX also triggered metabolic reprogramming toward aerobic glycolysis via the Akt–mTOR–HIF1α pathway, which was essential for the trained phenotype. Transcriptomic and functional analyses further revealed that the GPR183–STING axis mediated PTX-induced trained immunity. Inhibition of GPR183 impaired STING activation and suppressed functional responses in vitro. In a murine MRSA pneumonia model, PTX-trained mice showed reduced bacterial burden, preserved lung barrier integrity, and enhanced immune activation, all of which were reversed by GPR183 inhibition or STING deficiency. Collectively, our findings uncover a previously unrecognized immunomodulatory function of PTX and highlight the therapeutic potential of targeting the GPR183–STING axis to enhance trained immunity against resistant bacterial infections.

Neospora caninum is a major cause of abortion in cattle worldwide, leading to substantial economic losses in the livestock industry. As no effective drug or vaccine is currently available, a deeper understanding of the host immune response against N. caninum is essential for developing effective control strategies. The absent in melanoma 2 (AIM2) inflammasome is involved in host defense and regulation of disease pathology, while its role in N. caninum infection remains unclear. This study shows that N. caninum activates the AIM2 inflammasome in wild-type (WT) murine peritoneal macrophage (PMϕs), characterized by increased expression of AIM2, pro-IL-1β, caspase-1 p20, and IL-1β p17, along with elevated IL-1β secretion and cell death rates. Guanylate-binding proteins (GBPs) are involved in regulating AIM2 inflammasome activation. Here, we observed that both GBP2 and GBP5 were upregulated by N. caninum, but only GBP5 overexpression played a functional role, as its overexpression enhanced, whereas its knockdown significantly attenuated AIM2 inflammasome in WT PMϕs, suggesting N. caninum activates the AIM2 inflammasome in a GBP5-dependent manner. To further investigate the role of AIM2 in parasite infection, AIM2−/− mice were used. In AIM2−/− PMϕs, inflammasome activation was reduced, accompanied by increased parasite proliferation. In vivo, N. caninum-infected AIM2−/− mice exhibited higher parasite loads but showed increased survival rates, reduced macrophage recruitment, decreased levels of IFN-γ, and IL-18, and alleviated pathological damage. In summary, our findings demonstrate that the AIM2 inflammasome is activated by N. caninum in a GBP5-dependent manner and plays a dual role by restricting parasite proliferation while exacerbating disease pathology.

OBJECTIVE:This study aims to investigate the factors that influence the occurrence of complications following deep inferior epigastric perforator (DIEP) flap breast reconstruction, and to determine whether these complications have an impact on the patient's quality of life in China. METHODS:We collected clinical data from patients who underwent DIEP flap breast reconstruction at the Department of Breast, Affiliated Cancer Hospital of Zhengzhou University between December 2019 and December 2023. We analyzed the incidence of postoperative complications and their relationship with patient clinical data and surgical parameters. We also used the BREAST-Q 2.0 Chinese version scale to assess the impact of postoperative complications on patient-reported outcomes. RESULTS:A total of 109 patients underwent DIEP flap breast reconstruction, including 91 stage I reconstructions and 18 stage II reconstructions. Postoperative complications occurred in 26 cases (23.9%), including flap complications in 13 cases (11.9%) and abdominal donor-site complications in 13 cases (11.9%). Univariate and multivariate analyses showed that the overall incidence of complications was associated with high BMI and early surgery (P < 0.05). Flap complications were associated with high BMI, early surgery, and the use of internal mammary vascular branches as recipient vessels (P < 0.05). Abdominal complications were associated with previous abdominal surgery scars (P < 0.05). Approximately 20% of patients did not complete the BREAST-Q questionnaires (including the two patients who experienced total flap loss). BREAST-Q scores showed no significant differences between the surgical complication group and the no-complication group in terms of breast satisfaction, mental health, physical health-chest, physical health-abdomen, satisfaction with abdomen, sexual health, etc. (P > 0.05). CONCLUSION:Patients who underwent DIEP flap breast reconstruction revealed that high BMI, neoadjuvant therapy, and abdominal incision scars may influence postoperative complications. The limited follow-up data indicated that postoperative complications did not impact patient-reported outcomes.

Background:Changes in human epidermal growth factor receptor 2 (HER2) status following neoadjuvant chemotherapy (NAC) indicate tumor heterogeneity. Objective:Investigating the prognostic impact of the transition between HER2-low and HER2-zero may help eliminate the confounding effects of heterogeneity, thereby clarifying the prognostic significance of HER2-low status. Design:Retrospective analysis. Methods:Data were collected from patients with HER2-negative, early-stage breast cancer who did not achieve a pathological complete response after NAC. Cox regression models and Kaplan-Meier survival curves were employed to analyze disease-free survival (DFS) and overall survival (OS). Results:A total of 744 patients were included in the analysis, including 207 with HER2-zero and 537 with HER2-low pre-NAC. Among these, 46.9% (97/207) of the patients with HER2-zero transitioned to HER2-low, whereas 14.7% (79/537) of those with HER2-low transitioned to HER2-zero. Based on the HER2 status pre-NAC, there was no difference in prognosis between the HER2-zero and HER2-low groups. Patients with constant HER2-zero status had poorer OS than those who transitioned from HER2-zero to HER2-low (p = 0.025) in the hormone receptor-negative population, albeit no such result was observed in the hormone receptor-positive population. No significant difference in OS was observed between patients with constant HER2-low status and those who transitioned from HER2-low to HER2-zero. In addition, no significant differences were noted in the DFS across the groups. Multivariate analysis revealed that the constant HER2-zero status was associated with worse OS when compared with other HER2 statuses. Conclusion:HER2 transitions between low and zero expressions were frequently observed after NAC, exhibiting heterogeneity of the HER2 expression. Except for the worst OS in the constant HER2-zero, hormone receptor-negative subgroup, no significant differences were observed in the DFS and OS with respect to the changes of HER2-zero and HER2-low groups. The prognostic significance of HER2-zero and HER2-low changes after NAC requires further exploration through prospective studies.

Background: Our previous national-wide analysis in representative large samples identified molecular subtype of hormone receptor-positive/human epidermal growth factor receptor 2-positive (HR+/HER2+) accounting for 18.0% of all breast cancers (BC), and 25.4% of HR+/HER2+ early or locally advanced (EBC or LABC) patients received neoadjuvant therapy in the real-world setting in China. This study reported further results regarding short-term response and mid-term survival outcomes. Methods: A representative sample of 51 hospitals (31 cancer centers and 20 general hospitals) covering 27 provinces or municipalities from the National Cancer Information Database (NCID) in China was used. Anonymous individual patient data from electronic medical records (EMR) were retrieved to extract information on demographics, disease characteristics, clinical features, therapy modalities, and outcomes. HR+/HER2+ EBC or LBC patients initially diagnosed between 1 January 2019 and 31 May 2022 were included if they had (1) received surgery and adjuvant treatment and (2) had post-surgery pathologic reports. Descriptive statistics was used to illustrate the distribution of patients in different subgroups with or without neoadjuvant therapy. Survival probability was calculated by the Kaplan-Meier method. Results: 13,323 Chinese patients initially diagnosed with HR+/HER2+ EBC or LABC were identified during the study period. Most patients’ data were derived from tertiary hospitals (n = 13321 [99.98%]), Cancer Centers (n = 11212 [84.16%]), and second-tier cities (n = 10089 [75.73%]). For the clinical stage, patients with cT2 (58.87%), cN0 (45.83%), or cN1 (35.01%) tumors were predominated. 3,791/13323 patients received neoadjuvant therapy. Combinations of two anti-HER2 agents + Chemo (2089/3791) topped the list of neoadjuvant regimens, of which trastuzumab-pertuzumab (TP) + chemotherapy (Chemo) (1970/3791[52.0%]) was the most frequently used therapy, while TP+ a tyrosine kinase inhibitor (n = 41) was used less frequently. T+ Chemo was reported in 649 patients and Chemo only was documented in 980 patients. Compared to neoadjuvant T + Chemo, combinations of two anti-HER2 agents + Chemo yielded significantly higher total pathological complete response (tpCR, 29.86% vs. 49.14%) and breast pCR (bpCR, 34.39% vs. 53.30%), both p<0.0001. Generally, patients who achieved tpCR had a lower recurrence rate than those who did not. Neoadjuvant TP followed by adjuvant TP appeared to be the most selected sequential regimen, the recurrence rate is 2.6% (3-yr-DFS: 94.83%) for patients with tpCR and 5.4% (3-yr-DFS: 80.86%) for who without tpCR. For patients that received neoadjuvant TP, following adjuvant TP led to a lower recurrence rate than T (2.6% vs. 4.9% in tpCR patients and 5.4% vs. 15.9% in patients without tpCR). Conclusions: To our knowledge, this is the first and largest longitudinal real-world study focusing on perioperative therapy utilization patterns, and short-term and mid-term outcomes in HR+/HER2+ EBC or LABC patients in China. The study, whether in terms of geographical coverage, hospital level, number of patients population, or the study period (that followed the launch of pertuzumab, which is one of the current standard-of-care treatments for patients with HER2+ BC), can represent the up-to-date diagnosis and treatment status quo in China. Our results provide evidence from clinical practice to verify the remarkable pCR and DFS outcomes derived from perioperative dual HER2 blockade with TP. Disclosures: None of the authors has any financial relationships to disclose. Funding: This study was sponsored by Shanghai Roche Pharmaceuticals Ltd. Acknowledgments: This project was supported by the National Anti-Tumor Drug Surveillance System of National Cancer Center. Also thank Beijing Yiyong Technology Ltd. for statistical assistance. Support for third-party writing assistance for this abstract, provided by Content Ed Net (Shanghai) Co., Ltd. was provided by Shanghai Roche Pharmaceuticals Ltd., Shanghai, China. Citation Format: Zhenzhen Liu, Jiujun Zhu, Chengzheng Wang, Zhenduo Lu, Xiuchun Chen, Lianfang Li, Xianfu Sun, Chongjian Zhang, Jianghua Qiao, Min Yan. (Neo)adjuvant Therapy Patterns and Outcomes in Patients with HR-Positive/HER2-Positive Early or Locally Advanced Breast Cancer: a Real-World Study Using National Cancer Information Database, China [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 P3-11-12.

Previous studies indicate that HER2 protein expression and hormone receptor (HoR) status affect the sensitivity of HER2-positive breast cancer to neoadjuvant therapy, but it is unclear if sensitivity varies among subgroups defined by HER2 and HoR status. We examined 2 cohorts of patients, aged 18 to 80 years, with HER2-positive early breast cancer who underwent neoadjuvant therapy followed by surgery between January 1, 2009, and December 31, 2022: cohort 1 included 2648 patients, and cohort 2 had 141 patients with RNA expression data. Patients were divided into 4 groups based on immunohistochemical HER2 and HoR status: HER2(3+)/HoR-, HER2(3+)/HoR+, HER2(2+)/HoR-, and HER2(2+)/HoR+. We evaluated total pathological complete response (TpCR, defined as ypT0/is ypN0) rates, disease-free survival (DFS), and variations in PAM50 intrinsic subtypes across different subgroups. In cohort 1, HER2(3+)/HoR- had a higher TpCR rate (44.5%) than HER2(3+)/HoR+ (33.8%) (P < .001), HER2(2+)/HoR- (31.7%) (P = .013), and HER2(2+)/HoR+ (13.8%) (P < .001). DFS was similar across groups (P = .445). Trastuzumab or trastuzumab plus pertuzumab significantly improved TpCR rates and DFS in HER2(3+)/HoR- and HER2(3+)/HoR+ but not in HER2(2+)/HoR- and HER2(2+)/HoR+. Cohort 2 showed significant PAM50 subtype differences across these groups (P < .001). In conclusion, the responsiveness of HER2-positive breast cancer to neoadjuvant targeted therapy is significantly influenced by HER2 expression levels and HoR status, emphasizing the necessity of precision medicine approaches to tailor therapeutic strategies for improved clinical outcomes.