TPS653 Background: Hormone receptor–negative/HER2-positive breast cancer achieves high pathological complete response (pCR) rates with chemotherapy-based HER2-targeted therapy, whereas hormone receptor–positive (HR+)/HER2-positive disease consistently demonstrates lower pCR rates and substantial chemotherapy-related toxicity, representing an unmet clinical need. Antibody–drug conjugates (ADCs) may address this gap by enhancing HER2-directed cytotoxic delivery while potentially avoiding conventional chemotherapy. SHR-A1811 (ruikang-trastuzumab) is a next-generation HER2-directed ADC conjugated to a topoisomerase I inhibitor with a high drug-to-antibody ratio (≈6) and has demonstrated superior preclinical activity compared with trastuzumab emtansine. HER2-directed ADCs may be particularly advantageous in HR-positive/HER2-positive tumors, including those with HER2 immunohistochemistry (IHC) 2+ and in situ hybridization (ISH)–positive status, through bystander killing effects that may overcome heterogeneous or lower-level HER2 expression. Emerging evidence suggests that ADC activity is retained in HR-positive/HER2-positive breast cancer and may be enhanced when combined with pertuzumab, providing the rationale for evaluating neoadjuvant SHR-A1811 plus pertuzumab in this population. Methods: This prospective, open-label, single-arm phase II trial enrolls women aged > 18 and < 70 years with previously untreated stage II–III HR-positive/HER2-positive breast cancer. All patients receive neoadjuvant SHR-A1811 (4.8 mg/kg intravenously every 3 weeks) plus pertuzumab (840 mg loading dose followed by 420 mg every 3 weeks) for four cycles. Baseline BluePrint profiling classifies tumors as luminal or non-luminal. Treatment is adaptively tailored based on molecular subtype and RECIST v1.1 response after four cycles. Patients with luminal subtype and stable disease switch to a chemotherapy-free regimen of trastuzumab, pyrotinib (a HER2-directed tyrosine kinase inhibitor), dalpiciclib (a CDK4/6 inhibitor), and an aromatase inhibitor, while patients with luminal subtype achieving partial or complete response and all non-luminal tumors continue SHR-A1811 plus pertuzumab for two to four additional cycles before surgery. Circulating tumor DNA (ctDNA) is assessed at baseline, after four cycles, and preoperatively. The primary endpoint is pCR (ypT0/is ypN0); secondary endpoints include event-free survival, objective response rate, and safety, with exploratory analyses evaluating associations among molecular subtype, ctDNA dynamics, and treatment response. Clinical trial information: NCT07307287 .

IRX1 functions as a tumor suppressor in cervical cancer; however, its underlying mechanism remains unclear. In this study, we observed that IRX1 expression is frequently downregulated in cervical cancer cells owing to promoter hypermethylation. Functionally, IRX1 overexpression suppressed cell proliferation, migration, and invasion, whereas IRX1 knockdown enhanced these malignant phenotypes. Mechanistically, IRX1 directly bound to the ATP-citrate lyase (ACLY) promoter and recruited NME3, thereby forming a transcriptional repressive complex. This IRX1-NME3/ACLY axis inhibited de novo fatty acid synthesis, as reflected by reduced levels of acetyl-CoA, malonyl-CoA, triglycerides, cholesterol, and lipid droplets. Consistently, ACLY overexpression partially reversed the suppressive effects of IRX1 on lipid metabolism and tumor progression. Collectively, our findings reveal that IRX1 functions as a metabolic tumor suppressor by transcriptionally repressing ACLY-mediated lipogenesis.

591 Background: Premenopausal patients with locally advanced hormone receptor–positive, HER2-negative (HR+/HER2−) breast cancer are routinely recommended neoadjuvant chemotherapy (NAC) despite heterogeneous and often limited response. In advanced disease, endocrine therapy (ET) plus CDK4/6 inhibition has replaced chemotherapy as first-line treatment. Whether patients with poor early response to NAC may benefit from chemotherapy-sparing strategies remains unclear. We conducted a prospective response-adapted study integrating early chemosensitivity assessment with exploratory genomic profiling to guide neoadjuvant treatment selection. Methods: A total of 116 premenopausal patients with stage II-III HR+/HER2− breast cancer received two initial cycles of TAC chemotherapy (docetaxel, doxorubicin, and cyclophosphamide). Radiologic response was assessed after two cycles. Patients achieving partial response (PR) continued TAC. Patients with stable disease (SD) were randomized to either continue TAC (NAC) or switch to 16 weeks of ET consisting of dalpiciclib (CDK4/6 inhibitor), exemestane, and goserelin (NET). Whole-exome sequencing was performed in an exploratory subset. The primary endpoint was objective response rate (ORR). Results: After two cycles of TAC, 30 patients achieved PR, while 86 exhibited SD and were subsequently randomized. Among evaluable patients, the ORR was 68.3% in the NET group (41 evaluable patients) compared with 48.7% in the continued NAC group (39 evaluable patients), indicating a higher response rate with NET in tumors demonstrating poor early chemosensitivity. Exploratory genomic analyses further showed that NET-sensitive tumors were predominantly TP53 wild-type and lacked PIK3CA or AKT alterations, consistent with a highly endocrine-dependent biology. In contrast, nonresponders to NET frequently harbored TP53 mutations, often in combination with PIK3CA/AKT pathway alterations, whereas patients who responded to continued chemotherapy commonly exhibited TP53 or TTN mutations, suggesting a chemotherapy-responsive but endocrine-refractory phenotype. Conclusions: Taken together, our findings indicate that in premenopausal patients with stage II-III HR+/HER2− breast cancer who demonstrate suboptimal early response to intensive neoadjuvant chemotherapy, continued cytotoxic treatment may not be optimal for all patients. A response-adapted strategy integrating early functional assessment with genomic features, particularly TP53 and PI3K/AKT pathway status, distinguishes endocrine-sensitive from chemotherapy-sensitive disease. These results provide a biologically informed framework for neoadjuvant treatment selection and support biomarker-enriched randomized trials evaluating chemotherapy-sparing strategies in selected patients. Clinical trial information: NCT06009627 .

Background:Breast cancer liver metastasis (BCLM) is associated with substantial prognostic heterogeneity and poor survival outcomes. Existing staging systems and prognostic models have a limited capacity for individualized survival prediction for patients with newly diagnosed BCLM, highlighting the need for more accurate and clinically applicable predictive tools. This study aimed to develop a prognostic nomogram for patients with newly diagnosed breast cancer and liver metastases using Surveillance, Epidemiology, and End Results (SEER) database data (2010-2021). Methods:Ten stable prognostic variables-age; tumor size; brain, bone, and lung metastases; histological grade; chemotherapy; estrogen receptor (ER) status; progesterone receptor (PR) status; and human epidermal growth factor receptor-2 (HER2) status-were selected using four machine learning algorithms (Least Absolute Shrinkage And Selection Operator, Extreme Gradient Boosting, Decision Tree, and Random Forest). The SEER cohort was randomly divided into training (70%) and internal validation (30%) cohorts, with an independent external cohort for validation. These variables were incorporated into a multivariate Cox proportional hazards regression model to construct a nomogram. Model performance was evaluated using the concordance index (C-index), calibration curves, decision curve analysis (DCA), and area under the curve (AUC). Results:The C-indices for the training, internal validation, and external validation cohorts were 0.760, 0.740, and 0.787, respectively. The 1-, 3-, and 5-year AUCs were 0.777, 0.757, and 0.764 (training); 0.755, 0.769, and 0.754 (internal validation); and 0.727, 0.752, and 0.801 (external validation), respectively. The calibration curves indicated good agreement and DCA confirmed the clinical utility of the model. Conclusion:The proposed nomogram demonstrated robust predictive performance for patients with breast cancer and liver metastases and may provide valuable prognostic information, pending further validation.

BACKGROUND Breast cancer is the most frequently diagnosed malignancy in females globally, and total mastectomy commonly initiates substantial anxiety and depression symptomatology. Although previous studies have mainly evaluated breast reconstruction as a psychological intervention that achieves superior psychosocial outcomes, relatively limited research has investigated postoperative psychological distress as an influential factor in shaping patients’ cognition, attitudes and acceptance of reconstruction after mastectomy (especially from the perspective of Chinese patients, where a low rate of radical mastectomy being followed by immediate or delayed breast recon. AIM To investigate the prevalence of postoperative anxiety and depression symptoms in breast cancer patients and explore its associations with willingness, cognition, and attitudes toward breast reconstruction to provide evidence for improving mental health and quality of life. METHODS A total of 112 breast cancer patients receiving surgical management in Tianjin Medical University Cancer Institute and Hospital between October 2023 to October 2024 were enrolled in this retrospective study. The study utilized the Self-Rating Anxiety Scale (SAS) and Self-Rating Depression Scale (SDS) to measure anxiety and depression symptoms. Concurrently, patients Search of demand knowledge and comprehension based on breast reconstruction operative was explored. To analyze the correlations between anxiety-depression symptoms and willingness for breast reconstruction and their influencing factors, Pearson correlation analysis, multiple linear regression and multivariate logistic regression were performed. RESULTS Among 112 patients, the prevalence of anxiety symptoms was 42.86% (48/112), depression symptoms 39.29% (44/112), and anxiety-depression comorbidity 28.57% (32/112). The SAS score was 46.25 ± 10.82, and the SDS score was 48.73 ± 11.35. The cognition score for breast reconstruction was 18.73 ± 4.72, the attitude score was 44.82 ± 8.83, and the reconstruction intention rate was 32.14%. Correlation analysis showed that the SAS score was negatively correlated with the cognition score (r = -0.412, P < 0.01) and attitude score (r = -0.386, P < 0.01); the SDS score was negatively correlated with cognition score (r = -0.435, P < 0.01) and attitude score (r = -0.402, P < 0.01). Multiple regression analysis showed that anxiety-depression scores were independent negative influencing factors for cognition and attitude (P < 0.05). Logistic regression showed that anxiety score [odds ratio (OR) = 0.876, 95% confidence interval (CI): 0.812-0.945], cognition score (OR = 1.193, 95%CI: 1.040-1.461), and attitude score (OR = 1.340, 95%CI: 1.098-1.792) were independent predictors for reconstruction intention. CONCLUSION The prevalence of anxiety and depression symptoms in breast cancer patients after total mastectomy is high. Anxiety and depression symptoms are significantly associated with lower cognition levels and more negative attitudes, and demand for breast reconstruction. The more severe the anxiety and depression, the lower the cognition, the more negative the attitude, and the lower the willingness for reconstruction. Clinical practice should emphasize the assessment and intervention of mental health in breast cancer patients. Improving anxiety and depression symptoms may help enhance patients’ cognition and acceptance of breast reconstruction, ultimately improving quality of life.

The molecular mechanisms driving the occurrence and progression of breast cancer remain unclear, necessitating the identification of novel molecular biomarkers and therapeutic targets. This study aims to investigate the role of SLC9A3R2 (NHERF2) in breast cancer progression via an integrated multi-scale approach. Analysis of The Cancer Genome Atlas (TCGA) data revealed that SLC9A3R2 is upregulated at both protein and mRNA level in breast cancer tissues, related to advanced tumor stage and poor prognosis, especially in luminal subtypes. Functional enrichment analyses linked high SLC9A3R2 expression to epithelial-mesenchymal transition (EMT), estrogen response, and PI3K-AKT/MAPK signaling pathways. Additionally, SLC9A3R2 expression was negatively correlated with the infiltration level of CD8+ T cell as well as the expression of four main immune checkpoint molecules. Single-cell RNA sequencing analysis of patient samples revealed that SLC9A3R2-positive tumor epithelial cells mediate aberrant cellular communication with endothelial cells, fibroblasts, and macrophages via specific ligand-receptor pairs involving FN1, COL1A1, and COL1A2. Cell functional assays showed that knockdown of SLC9A3R2 significantly impaired the proliferation, migration, and invasion capacities of breast cancer cells. Our findings establish SLC9A3R2 as a key promoter of breast cancer progression, influencing both intrinsic oncogenic pathways and the extrinsic tumor microenvironment (TME), which provides a novel insight for breast cancer treatment.

Metabolic-epigenetic crosstalk accelerates breast cancer (BC) progression; however, the conduit linking glycolytic flux to chromatin remodeling remains incompletely defined. Here, we delineate a kinase-metabolism-epigenetic axis centered on the Mitogen-Activated Protein Kinase Associated Protein 1 (MAPKAP1, also known as SIN1). Single-cell transcriptomic profiling of highly invasive tumors identifies SIN1 as a central node co-enriched with epithelial-mesenchymal transition and proliferation programs. Biochemical mapping and mass spectrometry demonstrate that SIN1 scaffolds TTK to promote phosphorylation of lactate dehydrogenase A (LDHA) at Tyr239 (p-LDHA^239), thereby amplifying glycolysis and lactate production. The resulting lactate accumulation increases histone H3K18 lactylation (H3K18la), which, as shown by ChIP-seq, is enriched at the Solute Carrier Family 2 Member 3 (SLC2A3, also known as GLUT3) promoter, upregulating GLUT3 and enhancing glucose uptake, thus establishing a self-reinforcing SIN1/TTK/LDHA-H3K18la-GLUT3 feed-forward loop. Structure-function analyses using domain truncations, molecular docking, and high-throughput virtual screening nominate LR-90 as a small-molecule inhibitor of the SIN1/TTK/LDHA complex. LR-90 reduces p-LDHA^239, lactate levels, H3K18la occupancy at the GLUT3 promoter, glucose uptake, invasion, and tumor growth, and it synergizes with standard chemotherapy in patient-derived organoids and mouse xenografts. Clinically, elevated SIN1 expression is associated with adverse pathological features and inferior overall survival. Collectively, these findings link SIN1-mediated recruitment of TTK for LDHA phosphorylation to histone lactylation and GLUT3-driven metabolic reprogramming, and suggest that pharmacological disruption of this axis with LR-90, alone or in combination with standard chemotherapy, may offer a therapeutic strategy for high-glycolytic, high-lactate breast cancer.

Breast cancer (BRCA), a prevalent malignancy among women, significantly impacts survival quality and life expectancy, with rising incidence and mortality rates posing substantial psychological and economic burdens on patients and families. Current treatment modalities exhibit considerable variability in efficacy, often hindered by resistance and recurrence, thus emphasizing the urgent need for novel biomarkers and therapeutic targets. This study investigates the genomic characteristics of the APOBEC family genes across different BRCA subtypes and their influence on mutation profiles. Utilizing data from multiple databases, including The Cancer Genome Atlas (TCGA) and the Clinical Proteomic Tumor Analysis Consortium (CPTAC), SMC, and Metabric, we conducted a comprehensive analysis of APOBEC mutation enrichment scores (APMs) and tumor mutational burden (TMB).Our findings reveal that APMs are significantly elevated in BRCA compared to other cancers, with distinct variations among subtypes; specifically, HER2+ breast cancer exhibited the highest APMs while triple-negative breast cancer (TNBC) displayed the lowest. We also observed correlations between APMs and TMB, suggesting differential immune microenvironment interactions, particularly in HER2+ versus TNBC and Luminal subtypes. Furthermore, APMs demonstrated a significant association with DNA damage response pathways, with implications for treatment strategies. Our study subsequently investigates the predictive role of the APOBEC mutagenesis-related prognostic risk score (AMrs) in guiding targeted and immunotherapy combinations for different subtypes of BRCA, specifically TNBC, Luminal, and HER2+ breast cancer. By leveraging a multi-center database, we seek to validate the correlation between AMrs scores and the sensitivity of these BRCA subtypes to immunotherapy. Based on in vivo experiments in mice, our research highlights that the administration of specific agents—AZD3759 for HER2+, Vorinostat for TNBC, and SGC0946 for Luminal—when combined with anti-PD-1 therapy, not only boosts therapeutic effectiveness but also transforms the immunological environment within tumors. This synergistic approach led to notable reductions in tumor volume and an increase in cytotoxic T cell density in in vivo and in vitro experiments, further validating the role of AMrs scores in tailoring treatment modalities across BRCA subtypes.Overall, our study elucidates the critical role of APOBEC family genes in BRCA heterogeneity, highlighting their potential as biomarkers for personalized therapeutic approaches and pointing towards future research directions in integrating APOBEC-related mechanisms with immunotherapy.

BACKGROUND: Tumor cells rely on enhanced glycolytic capacity to facilitate cell growth and progression. However, the molecular mechanisms governing glycolysis in triple-negative breast cancer (TNBC) remain largely elusive. In this study, we elucidate the role of OTUB2 in regulating glycolysis in TNBC and delve into the mechanisms. METHODS: We utilized The Cancer Genome Atlas (TCGA) dataset to analyze the expressions of OTUB2, EIF4A3, and TPI1 in breast cancer tissues and specifically in triple-negative breast cancer (TNBC) tissues. qPCR and western blot experiments were performed to confirm the protein expressions of OTUB2, EIF4A3, and TPI1 in TNBC tissues and cell lines. Subsequently, overexpression and knockdown experiments followed by cell functional assays were conducted to elucidate the impact of OTUB2 on EIF4A3/TPI1-mediated TNBC malignant progression and related molecular mechanisms. Finally, a xenograft mouse model was established to verify the effect of OTUB2 in vivo. RESULTS: TCGA database indicated highly expressions of OTUB2, EIF4A3, and TPI1 in breast cancer tissues and TNBC tissues. Consistently, the mRNA and protein expressions of OTUB2, EIF4A3, and TPI1 were increased in TNBC tissues and cell lines, as compared to para-carcinoma tissues and MCF10A cells. OTUB2 knockdown inhibited cell proliferation, migration and invasion, and decreased glucose uptake, ATP level, lactate production, and ECAR, while the OTUB2 overexpression exhibited the opposite trends. Further data elucidated that OTUB2 stabilized the EIF4A3 protein via deubiquitination, and EIF4A3 interacted with TPI1 to stabilize its mRNA. Overexpression of EIF4A3 exacerbated TNBC malignant activities and glycolysis, while silencing TPI1 reversed these effects. In vivo, the knockdown of OTUB2 significantly inhibited tumor growth in a xenograft mouse model. CONCLUSIONS: We conclude that OTUB2 deubiquitinates and stabilizes EIF4A3 to promote TNBC progression via TPI1-mediated glycolysis of tumor cells.

Background 4-HNE is a lipid peroxidation product involved in oxidative stress, tumor microenvironment remodeling, and tumor progression. This study aimed to characterize the cellular distribution, prognostic relevance, and functional roles of 4-HNE-related molecular features in lung adenocarcinoma. Methods 4-HNE-related targets were collected from ChEMBL and SwissTargetPrediction, followed by enrichment, differential expression, and survival analyses in TCGA-LUAD. A HNE_score was constructed using single-cell RNA-seq data. Cell-cell communication, fibroblast trajectory, transcription factor activity, spatial transcriptomics, machine learning, molecular docking, virtual knockout, and EdU assays were further performed. Results A total of 1,280 4-HNE-related candidate targets were identified and were mainly associated with xenobiotic response, PPAR signaling, estrogen signaling, and chemical carcinogenesis-related pathways. At the single-cell level, higher HNE_score values were mainly observed in macrophage, epithelial, and fibroblast populations. The HNE_high state was associated with enhanced stromal communication and a matrix-remodeling pattern involving fibroblasts, epithelial cells, and myeloid cells, together with enrichment of CTHRC1-positive myofibroblastic cancer-associated fibroblast features. RRM2 and CYP4B1 were identified as stable HNE_score-related prognostic candidates with opposite prognostic associations. RRM2 knockdown reduced DNA synthesis and proliferation in PC9 cells, supporting its functional relevance in lung adenocarcinoma. Conclusion This study provides a multilayered map of 4-HNE-related cellular states in lung adenocarcinoma and links 4-HNE activity to stromal remodeling, altered cell-cell communication, and prognostic gene screening. RRM2 and CYP4B1 may represent key HNE-related prognostic candidates, with RRM2 showing functional relevance in tumor cell proliferation.

BackgroundBreast cancer heterogeneity is influenced by tumor grade, molecular subtype, and modifiable lifestyle factors such as diet and nutritional status. Tumor aggressiveness and oxidative stress may be influenced by dietary habits and serum nutritional profiles, according to new research.AimThe purpose of this study was to assess the relationship between oxidative stress markers, dietary patterns, serum nutritional profiles, and breast cancer tumor features, such as tumor grade and molecular subtype.MethodologyUsing validated questionnaires, the tumor grade, molecular subtype, serum nutrients (vitamins, trace elements, lipids, oxidative stress indicators), and food intake of 293 female patients with breast cancer were evaluated in this retrospective analysis. Dietary patterns were found using principal component analysis, and statistical analyses included correlation matrices and logistic regression.ResultsThe molecular subtypes of the tumors were Luminal A (38.2%), Luminal B (24.9%), HER2-enriched (21.3%), and triple-negative (15.7%). The tumor grades were Grade I (29.8%), II (45.5%), and III (24.7%). With tumor grade, oxidative stress (MDA) rose and antioxidant nutrients decreased (p < 0.01). Plant-based, Western, Mixed, and Mediterranean-like eating patterns were found. While the Mediterranean-like diet was beneficial (OR = 0.60, p = 0.041), excessive adherence to the Western diet was linked to increased risks of aggressive tumors (OR = 2.30, p = 0.003). Antioxidant nutrients and adherence to the Mediterranean-like diet were shown to be favorably correlated; MDA was positively correlated with the Western pattern.ConclusionAntioxidant-rich Mediterranean-like dietary pattern showed inverse association with aggressive tumor features, suggesting potential protective biological relationship while Western dietary pattern was positively associated with oxidative stress and lower circulating antioxidant nutrients. Personalized nutrition methods to improve breast cancer prognosis may be informed by the integration of dietary and biochemical assessment.

Given the lack of effective targeted therapeutic options for triple-negative breast cancer (TNBC), there is an imperative demand for innovative treatment approaches, with ferroptosis standing out as a promising direction. This study identifies HSPA6 as a key ferroptosis sensitizer in TNBC. Mechanistically, HSPA6 binds to NF-κB p65, inhibits its nuclear translocation and Ser468 phosphorylation, thereby suppressing transcription of the lipogenic enzyme FASN and downregulating phospholipid-remodeling enzymes LPCAT1/cPLA2. This dual inhibition enriches membrane phospholipids with polyunsaturated fatty acids, heightening peroxidation susceptibility and triggering ferroptosis. Concurrently, HSPA6-mediated suppression of lipogenesis depletes palmitate, thereby attenuating ANKIB1 palmitoylation and inhibiting its E3 ligase activity. This impairs K48-linked ubiquitination and degradation of HSPA6, forming a stabilizing positive feedback loop. Our study uncovers a HSPA6-p65-FASN-ANKIB1 axis linking lipid metabolism to ferroptosis, offering a novel TNBC therapeutic target.

Breast cancer remains a major threat to women's health and survival worldwide. Iroquois homeobox 1 (IRX1), a developmentally regulated transcription factor, acts as a tumor suppressor in several cancers. However, its mechanistic role in breast cancer remains elusive. In this study, we demonstrate that IRX1 is downregulated in breast cancer tissues and cell lines due to promoter hypermethylation. IRX1 functioned as a tumor suppressor both in vitro and in vivo. Mechanistically, IRX1 interacts with NME1 and promotes its nuclear localization. Subsequently, NME1 facilitates the transcriptional regulation of ACACA by IRX1. The IRX1-NME1 axis modulates de novo fatty acid synthesis and breast cancer progression by targeting ACACA. In conclusion, our findings reveal that the IRX1- NME1/ACACA axis plays a critical role in de novo fatty acid synthesis and breast cancer progression, providing new insights into gene regulatory interactions and highlighting its potential as a novel therapeutic target for breast cancer.

Pathologic complete response (pCR) after neoadjuvant chemotherapy and dual HER2 blockade is associated with improved outcomes in HER2-positive breast cancer, but treatment response remains heterogeneous. We aimed to develop and externally validate an interpretable model based on routine clinicopathological biomarkers to predict pCR and identify clinically meaningful response states. In this multicenter retrospective study, 1,082 patients with HER2-positive breast cancer treated with neoadjuvant chemotherapy and dual HER2 blockade at two Chinese centers were included for model development and internal validation. An independent cohort of 307 patients from a third center was used for external validation. Machine-learning models were developed using routinely available pretreatment clinicopathological variables. Model performance was evaluated using the area under the receiver operating characteristic curve (AUC). Probability-landscape analyses were performed to characterize biomarker-defined response states associated with pCR. The final gradient boosting machine model achieved AUCs of 0.78 in internal testing and 0.70 in external validation. Probability-landscape analyses identified distinct response states with substantially different pCR probabilities. Low hormone receptor expression combined with HER2 immunohistochemistry (IHC) 3 + status defined a high-probability pCR state, whereas high hormone receptor expression, low Ki-67 expression, and HER2 IHC 2+/fluorescence in situ hybridization (FISH)-positive disease defined persistently low-probability states. Among baseline node-positive patients who achieved breast pCR, residual nodal disease was observed in only 6.1

Our objective was to investigate breast–axillary pathological response discordance after neoadjuvant chemotherapy (NACT) in triple-negative breast cancer (TNBC). We retrospectively analyzed 651 patients with TNBC who received NACT followed by surgery. Four composite response patterns were defined by breast pathological complete response (BpCR) and nodal pathological complete response (NpCR). Logistic regression assessed factors associated with residual axillary disease in patients with BpCR and with NpCR in patients without BpCR. Era-stratified analyses compared 2014–2019 and 2020–2024. Discordance occurred in 30.6

Background Prepectoral implant-based breast reconstruction (IBBR) may be achieved by direct-to-implant (DTI) or tissue expander-to-implant (TEI) approaches, yet the preferred strategy is not well established. This study represents comparative analysis of DTI versus TEI in the setting of prepectoral IBBR followed by postmastectomy radiation therapy (PMRT), evaluating both complications and patient-reported outcomes (PROs). Methods This retrospective study enrolled breast cancer patients receiving prepectoral IBBR followed by PMRT from December 2018 to December 2024. They were assigned to either the DTI-PMRT group (immediate implant + PMRT) or the TEI-PMRT group (immediate tissue expander + PMRT + subsequent implant exchange). Intergroup comparisons were made for complications, risk factors, reconstructive failure, and PROs, the latter evaluated by the Breast-Q. Results Among the 217 enrolled patients, 146 completed follow-up. The TEI-PMRT group had significantly higher rates of reconstructive failure (14.5% vs 3.7%; P = 0.008), postoperative infection (13.6% vs 3.7%; P = 0.015), and severe capsular contracture (30.2% vs 14.0%; P = 0.030) than the DTI-PMRT group. TEI was independently associated with an increased risk of reconstructive failure (adjusted odds ratio [OR] = 3.71, adjusted P = 0.011), postoperative infection was strongly associated with reconstructive failure( P <0.001). Although overall satisfaction was comparable between the groups, the TEI-PMRT group showed a trend toward improved sexual satisfaction after permanent implant replacement ( P = 0.001). Conclusions TEI-PMRT was associated with higher failure and severe contracture rates than DTI-PMRT, but postoperative PROs were comparable. Thus, primary DTI may be considered for prepectoral reconstruction.

Background:Prepectoral implant-based breast reconstruction (BR) via single-port endoscopic axillary approach reduces visible scarring and incision-related complications. TILOOP mesh may improve implant support and aesthetics, but its added value remains uncertain. This study evaluated outcomes, complications, and patient satisfaction with mesh use. Methods:A retrospective cohort of 383 patients (165 mesh vs. 218 no-mesh) undergoing immediate prepectoral BR via single-port endoscopy [2020-2022] was analyzed. Outcomes included surgical parameters, complications at 30 days/12 months, oncological results at 36 months, and Breast Reconstruction Evaluation and Satisfaction Questionnaire (BREAST-Q) satisfaction. Results:Baseline features were balanced. The mesh group showed slightly lower mean postoperative pain scores and higher breast satisfaction scores; however, these differences did not reach statistical significance (P>0.05). Mesh use was associated with greater blood loss (98.1±62.2 vs. 91.2±42.2 mL, P<0.05) and longer hospitalization (8.4±4.1 vs. 5.6±2.8 days, P<0.05). There were no significant differences in complication rates, psychological well-being, or physical function between groups. Subgroup analysis indicated that patients with larger breast volumes tended to derive greater aesthetic and structural benefit from mesh use, though these findings should be interpreted cautiously. Conclusions:Mesh-assisted prepectoral reconstruction demonstrated comparable safety outcomes to non-mesh reconstruction, with a trend toward reduced postoperative pain and improved breast satisfaction but without statistically significant differences. Mesh use was associated with higher blood loss and longer hospitalization. Overall, mesh application should be individualized based on breast volume, reconstructive goals, and patient-specific factors.

Background: HER2+/HR+ breast cancer exhibits unique clinical and biological characteristics due to the interplay between HER2 and HR signaling pathways, rendering chemotherapy-free anti-HER2 therapy a potential treatment avenue. Based on findings from the ALTERNATIVE study, the NCCN guidelines recommend the combination of aromatase inhibitors with lapatinib and trastuzumab for treating HER2+/HR+ advanced breast cancer. Additionally, the PHEDRA and NEOSPHERE studies have shown that a pyrotinib (anti-HER2 TKI)-containing regimen in the neoadjuvant setting significantly enhances tpCR rates (17.7% vs. 6%) in HER2+/HR+ breast cancer. This study aims to evaluate the efficacy and safety of pyrotinib combined with trastuzumab and an aromatase inhibitor (AI) in the neoadjuvant treatment of HER2+/HR+ breast cancer (NCT05885776). Methods: This investigation is a single-arm, multi-center phase II exploratory study. The inclusion criteria encompass female patients aged 18 to 75 years, diagnosed with stage II to IIIA HER2-positive (IHC score 3+ or 2+ and ISH positive), ER > 10% invasive breast cancer. Participants received 6 cycles of pyrotinib (400 mg orally daily), trastuzumab (initially 8 mg/kg, followed by 6 mg/kg intravenously on day 1, Q3w), and an AI (either letrozole 2.5 mg orally daily or anastrozole 1 mg orally daily). Premenopausal or perimenopausal patients also received ovarian function suppressants. Post-surgery radiotherapy and adjuvant treatments were individualized. Primary endpoint assessed was tpCR (ypT0/is ypN0), while secondary endpoints included ORR, breast conservation rate, and safety profile. The study adopted Simon's two-stage optimal design, testing H0 (tpCR ≤ 10%) against H1 (tpCR > 25%), with a one-sided significance level of 0.05 and 80% power. Initially, 18 patients were recruited. If ≤2 achieved tpCR, the null hypothesis would be accepted, and the study terminated; otherwise, recruitment would continue to a total of 43 patients. Treatment efficacy is deemed achieved if ≥8 patients reach tpCR. Results: From August 23, 2022, to June 4, 2024, 22 patients were enrolled. Among these, 86.4% (19/22) had ER ≥ 50%, 72.7% (16/22) exhibited Ki67 ≥ 30%, 31.8% (7/22) were stage III, 18.2% (4/22) were stage T3, and 68.2% (15/22) had positive lymph nodes. To date, 15 patients have undergone surgery, with 20% (3/15) achieving tpCR, thus meeting the pre-defined threshold for progressing to the second recruitment stage. The breast conservation rate stands at 46.7% (7/15). Major adverse reactions included diarrhea, stomach discomfort, reduced appetite, and nausea. No grade 4 adverse events occurred; grade 3 adverse events comprised diarrhea (22.7%) and elevated creatinine levels (4.5%). Conclusion: The results from the initial stage of this study suggest that the combination of pyrotinib, trastuzumab, and AI in the neoadjuvant setting for HER2+/HR+ breast cancer provides the anticipated efficacy with a manageable safety profile. Consequently, the study will continue to enroll up to 43 patients. Citation Format: Jie Ge, XiangChao Meng, Xin Wang, Xuchen Cao, Min Zhang, Bin Zhang, Ying Zhao, YongSheng Jia, QingJuan Yao, Lin Li. {Title} [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 P5-07-23.

8MW0511 is a novel, long-acting recombinant human granulocyte-colony stimulating factor (G-CSF) produced by the fusion of the N-terminus of highly active modified G-CSF with the C-terminus of human serum albumin (HSA). Current G-CSF treatments require frequent administration and have limitations in efficacy and convenience, highlighting the need for a longer-acting alternative with fewer injections and improved outcomes. Here, we report a phase III study comparing the efficacy and safety of 8MW0511 with those of the approved PEG-rhG-CSF. Patients with breast cancer were randomized at a 2:1 ratio to receive either 8MW0511 or PEG-rhG-CSF after four cycles of standard chemotherapy with docetaxel and cyclophosphamide, with or without doxorubicin. The primary efficacy endpoint was to evaluate the duration of severe neutropenia (DSN) between 8MW0511 and PEG-rhG-CSF during the first cycle. Eligible patients were enrolled and randomly assigned to receive either 8MW0511 (n = 328) or PEG-rhG-CSF (n = 164). During the first cycle, the average DSN was 0.24 days for the 8MW0511 group and 0.25 days for the PEG-rhG-CSF group. The mean difference in DSN [-0.02 days (95