Cancer Research and Treatment

Distinct Evolutionary Dynamics of HER2-Ultralow Versus HER2-Null from Residual to Metastatic Disease in Non-pCR Breast Cancer: Shunan Wang, Jingjing Liu, Tong Liu, Shichao Zhang, Xinyu Liu, Yu Liu, Jin Zhang; Received March 22, 2026 Accepted May 11, 2026 Published online May 12, 2026; DOI: https://doi.org/10.4143/crt.2026.0302 [Accepted]

Abstract PDF: Purpose
In breast cancer (BC) patients without pathological complete response (pCR) after neoadjuvant therapy, residual disease drives recurrence. The HER2 spectrum now includes HER2-low and HER2-ultralow. HER2-low tumors are eligible for HER2-targeted antibody-drug conjugates (ADCs), while T-DXd is approved for HR-positive HER2-ultralow metastatic BC after endocrine therapy. Evolution patterns of HER2-ultralow versus HER2-null from residual to metastatic disease remain unclear.
Materials and Methods
We retrospectively studied 488 non-pCR patients with refined HER2 classification; 92 with HER2-0 residual disease formed the analytic cohort for HER2-ultralow/HER2-null comparison. HER2 status was tested in paired residual and metastatic lesions. Logistic regression was used to identify factors linked to HER2 evolution.
Results
In the 92‑patient HER2‑0 analytic cohort, HER2-ultralow (46.7% of HER2-0) converted more frequently to HER2-low than HER2-null (51.2% vs 30.6%, p=0.045). This difference remained statistically significant in the multivariable logistic regression model. In the full 517-patient contextual cohort, HER2 expression gain in recurrent/metastatic lesions was independently associated with poorer post-recurrence survival (PRS) (adjusted HR=1.74, p=0.009). In the 488-patient primary cohort, conversion from HER2-0 to HER2-low was also associated with poorer PRS (adjusted HR=2.18, p<0.001). The broader HER2 expression evolution in the full 517‑patient cohort and the primary 488‑patient refined HER2 cohort was consistent with the core finding from the 92‑patient HER2‑0 analytic cohort and supported its biological plausibility.
Conclusion
HER2-ultralow shows distinct evolution and high HER2-low conversion potential, affecting ADC eligibility. Routine HER2-0 subclassification and metastatic HER2 reassessment appear clinically useful and warrant prospective validation.

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Toward Sustainable Care in HER2-Positive Metastatic Breast Cancer: Emerging Evidence for Treatment De-escalation: Matilda Xinwei Lee, Soo Chin Lee; Received October 16, 2025 Accepted April 23, 2026 Published online April 23, 2026; DOI: https://doi.org/10.4143/crt.2025.1131 [Accepted]

Abstract PDF: Major advances in the management of HER2-positive (HER2+) metastatic breast cancer (MBC) have been achieved through treatment intensification with novel HER2-targeted agents and combination strategies, resulting in substantial survival gains. However, indefinite exposure to systemic therapy imposes cumulative toxicity, financial strain, and quality-of-life burdens. In contrast, the concept of treatment de-escalation, aimed at maintaining disease control with less intensive therapy, has only recently emerged as a complementary paradigm. This review highlights two evolving avenues of treatment de-escalation. First, in hormone receptor-positive (HR+)/ HER2+ disease, randomized trials have demonstrated that combining HER2 blockade with endocrine therapy and CDK4/6 inhibitors can overcome endocrine resistance, offering a chemotherapy-sparing approach with outcomes comparable to chemotherapy or antibody-drug conjugates. Second, in long-term responders, retrospective analyses and ongoing prospective trials are evaluating whether discontinuation of prolonged maintenance HER2 therapy can safely reduce treatment burden while preserving disease control, with the added potential for effective rechallenge upon relapse. Together, these developments suggest that treatment de-escalation represents a rational and necessary treatment strategy. Future progress will depend on biomarker-driven patient selection and prospective validation. Redefining success in HER2+ MBC to include not only survival but also quality of life and sustainability represents an important step toward patient-centered cancer care.

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Spatial Interactions of CD103+ Tissue-Resident Memory T Cells in the Tumor Periphery Are Associated with Clinical Outcomes in Triple-Negative Breast Cancer Following Neoadjuvant Chemotherapy: Hyun Lee, Byung-Kwan Jeong, Gyungyub Gong, Miseon Lee, Hee Jin Lee; Received December 29, 2025 Accepted March 14, 2026 Published online March 18, 2026; DOI: https://doi.org/10.4143/crt.2025.1416 [Accepted]

Abstract PDF Supplementary Material: Purpose
Triple-negative breast cancer (TNBC) is an aggressive subtype with poor prognosis. CD103+ tissue-resident memory T (TRM) cells are crucial for anti-tumor immunity in TNBC. We investigated whether their spatial interactions with other T-cells influence clinical outcomes, particularly following neoadjuvant chemotherapy (NAC).
Materials and Methods
This retrospective study analyzed 182 TNBC patients (98 NAC-treated; 84 non-NAC). Using Opal™ multiplex immunohistochemistry data and the Spatial Image Analysis of Tissues (SPIAT) R package, we analysed spatial interactions between CD103+ cells and other T cell subsets (CD45RO, CD8, CD4, PD-1) in central/peripheral tumor regions. Normalized mixing score (NMS) quantified spatial interactions.
Results
NMS-based clustering revealed two distinct CD103+ cell interaction patterns—Cluster 1 (low NMS) characterized by weaker and Cluster 2 (high NMS) by stronger spatial interactions between CD103+ and other T cell subsets. In the NAC group, Cluster 2 in the tumor periphery was associated with lower pathologic stage (p=0.002), higher stromal tumor-infiltrating lymphocyte level (p=0.031), and significantly improved recurrence-free survival (p=0.028) and overall survival (p=0.018) compared to Cluster 1. Central tumor region clustering patterns had no association with prognosis. No significant survival-related differences were observed in the non-NAC group according to NMS-based clustering.
Conclusion
Spatial interaction patterns between CD103+ and other T cell subsets in the tumor periphery influence clinical outcomes in NAC-treated TNBC patients. Analysing such spatial relationships between T cells, rather than their presence alone, may provide additional prognostic information for patients undergoing NAC.

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A Phase I/II Trial to Evaluate the Safety and Efficacy of Continuous Positive Airway Pressure in Volumetric Modulated Arc Therapy for Breast Cancer: Jung Bin Park, Tosol Yu, Jaeman Son, Chul-Won Choi, Seho Kwon, Hyun-Woo Shin, Hak Jae Kim, Ji Hyun Chang; Received November 22, 2025 Accepted January 25, 2026 Published online January 26, 2026; DOI: https://doi.org/10.4143/crt.2025.1281 [Accepted]

Abstract PDF: Purpose
This phase I/II study aimed to evaluate the tolerability and the organ-sparing effects of continuous positive airway pressure (CPAP) in breast cancer radiotherapy (RT).
Materials and Methods
We conducted a prospective, single-institutional trial approved by the Ministry of Food and Drug Safety of South Korea. Patients with breast cancer who received postoperative RT underwent 4D-CT simulation and treatment planning under both free breathing (FB) and CPAP-assisted breathing (WC), with a target pressure of 20 cm H₂O. Adverse events (AEs) were evaluated, and dosimetric parameters of organs at risk and heart position change were compared between the FB and WC arms.
Results
Among 20 enrolled patients, four withdrew due to discomfort during simulation. During the trial, no CPAP-related AEs greater than grade 2 were observed. Compared to FB, CPAP reduced the mean heart dose by 33.8% (p < 0.001), as well as V₅–V₃₀ for both the left ventricle and left anterior descending artery (all p < 0.05). It also led to significant reductions in V₅–V₄₀ and the mean ipsilateral lung dose, including a 4.4% reduction in V₂₀ (all p < 0.001). The heart centroid shifted rightward (4.8 mm), ventrally (8.1 mm), and caudally (16.3 mm) with CPAP, displacing the heart away from the RT field.
Conclusion
CPAP demonstrated both safety and efficacy for breast cancer RT, achieving significant reductions in cardiac and pulmonary radiation exposure. These findings support further investigation of CPAP as a novel respiratory motion management strategy. Future studies are warranted to identify optimal CPAP pressure levels to facilitate broader clinical implementation.

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Salidroside-Loaded, TMTP1-Modified CSC-Exosomes Reprogram the PI3K/AKT/mTOR Axis to Overcome PD-1 Resistance in Breast Cancer: Faxiang Yin, Xin Jin, Ligong Zhang, Qiang Xie, Jun Qian; Received August 8, 2025 Accepted January 11, 2026 Published online January 14, 2026; DOI: https://doi.org/10.4143/crt.2025.849 [Accepted]

Abstract PDF: Purpose
To elucidate how Salidroside-loaded, oligopeptide-modified tumor exosomes (Salidroside@T-exo) rewire the PI3K/AKT/mTOR axis to remodel the immune microenvironment (IME) and reverse acquired PD-1 resistance in breast cancer.
Materials and Methods
CSC-exosomes were surface-engineered with TMTP1 peptide and electroporated with Salidroside. PD-1-resistant MA782/5s-8101-R cells and an orthotopic mouse model were used. Multi-omics, flow cytometry, ELISA, immunofluorescence, in vivo imaging, and molecular assays examined immune and signaling outcomes.
Results
Salidroside@T-exo restored T-cell IFN-γ and GZMB secretion, suppressed CD8+ T-cell apoptosis, and inhibited p-PI3K/p-AKT/p-mTOR in T cells. CSC migration, invasion, and stemness (OCT4, NANOG, SOX2) were markedly reduced. Tumor growth, Ki-67 index, and CSC frequency dropped while TUNEL-positive cells rose.
Conclusion
Salidroside@T-exo reverses PD-1 blockade resistance by simultaneously inhibiting PI3K/AKT/mTOR signaling in T cells and eradicating breast CSCs, offering a clinically translatable strategy for refractory breast cancer immunotherapy.

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Radiomics-Based Prediction of Lymphedema after Radiotherapy in Breast Cancer: Integrating Clinical and Dosimetric Features: Jae Sik Kim, Seung Hyuck Jeon, Bum-Sup Jang, Jin Ho Kim, Ji Hyun Chang, Dowook Kim, Kyung Hwan Shin; Received September 9, 2025 Accepted January 11, 2026 Published online January 13, 2026; DOI: https://doi.org/10.4143/crt.2025.985 [Accepted]

Abstract PDF: Purpose
Arm lymphedema is a common, debilitating complication in patients with breast cancer undergoing postoperative radiotherapy (PORT). Although clinical and dosimetric factors have been used for risk prediction, radiomics offers a novel approach for improving the predictive accuracy.
Materials and Methods
We designed a predictive model for lymphedema using clinical, dosimetric, and radiomic features. We included 532 patients (399 training and 133 testing) who underwent breast cancer surgery followed by PORT. Radiomic features were extracted from axillary levels I, II, III, and supraclavicular regions, which were automatically contoured on PORT-planning computed tomography scans. Least absolute shrinkage and selection operator regression was used for feature selection. Model performance was evaluated using the area under the curve (AUC), accuracy, sensitivity, and specificity.
Results
The Combined model integrating clinical, dosimetric, and radiomic features showed higher predictive performance (AUC: training 0.783, test 0.767, total 0.779) than the Clinical/Dosimetric (AUC: training 0.730, test 0.671, total 0.717) and Radiomics-only (AUC: training 0.721, test 0.668, total 0.708) models. The Combined model also achieved a higher accuracy (training 78.9%, test 78.2%, total 78.8%), sensitivity (training 74.6%, test 62.5%, total 72.0%), and specificity (training 79.7%, test 80.3%, total 79.9%) than the other models. DeLong’s test confirmed that the Combined model significantly outperformed the Clinical/Dosimetric model (p=0.036 in training and p=0.010 in all datasets).
Conclusion
Integrating radiomic features with clinical and dosimetric factors showed potential to enhance lymphedema prediction in patients with breast cancer receiving PORT. This model can potentially guide personalized treatment strategies and improve patient outcomes.

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Identification of Tumor Doubling Time-Related Subtypes and Construction of Risk Models to Predict Prognosis and Immunological Features in Breast Cancer: Yuehong Xu, Hongbo Li, Lulu Yang, Rongfei Wang; Received August 27, 2025 Accepted December 30, 2025 Published online December 31, 2025; DOI: https://doi.org/10.4143/crt.2025.948 [Accepted]

Abstract PDF: Purpose
Breast cancer (BRCA)'s molecular heterogeneity complicates prognosis and treatment. Tumor Doubling Time (TDT), a critical growth rate metric with clinical and prognostic significance, offers untapped potential as a biomarker to decode heterogeneity and improve therapeutic strategies.
Materials and Methods
Based on transcriptomic and clinical data from TCGA and GEO, this study analyzed BRCA. Through differential expression and survival analyses, differentially expressed tumor doubling time-related genes (TDTRGs) with prognostic significance were identified. Consensus clustering using these genes defined two molecular subtypes. A prognostic risk model was constructed and validated through LASSO and multivariate Cox regression. Comprehensive evaluation was performed on these molecular subtypes and risk groups, encompassing immune infiltration (ssGSEA, CIBERSORT, ESTIMATE), mutational burden, response to immunotherapy (IMvigor210), and drug sensitivity (CellMiner, pRRophetic).
Results
This study constructed and validated an 8 gene prognostic risk model demonstrating robust predictive performance in both training (AUCs: 1-year=0.703, 3-year=0.693, 5-year=0.671) and validation cohorts. The low-risk group showed significantly enhanced immune cell infiltration, elevated immune checkpoint expression, and improved response to immunotherapy. Conversely, the high-risk group displayed increased tumor purity, metabolic reprogramming (e.g., respiratory electron transport), genomic instability, higher tumor mutational burden, and differential drug sensitivity (e.g., resistance to Gemcitabine/Tamoxifen).
Conclusion
This study establishes a novel TDTRGs framework for BRCA molecular classification and validated prognostic stratification. It reveals key disparities in immune microenvironment and genomic stability, enhancing understanding and guiding personalized therapeutic strategies.

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Redefining HER2 in Breast Cancer: From Conventional Positivity to Low and Ultralow in the New Era of Antibody-Drug Conjugates: Jiwon Koh, Seock-Ah Im; Cancer Res Treat. 2026;58(1):15-25. Published online December 18, 2025; DOI: https://doi.org/10.4143/crt.2025.1182

Abstract PDF PubReader ePub

Human epidermal growth factor receptor 2 (HER2) has evolved from a poor prognostic factor to one of the most impactful predictive biomarkers in oncology. The introduction of trastuzumab established HER2 as a binary determinant of therapy, with HER2 immunohistochemistry (IHC) becoming the treatment-guiding diagnostic assay. However, the emergence of antibody-drug conjugates (ADCs), particularly trastuzumab deruxtecan, has challenged this paradigm by demonstrating activity in tumors with low and even ultralow HER2 expression. This review outlines the evolution of HER2 testing, from its historical discovery and early assay variability to the ADC era, where categories such as HER2-low and HER2-ultralow have emerged. We highlight key challenges: poor reproducibility at the lower end of IHC scoring, instability of HER2 status across timepoints and between primary and metastatic tumors, and no consistent biological distinction between low, ultralow, and null. Efforts to improve reliability—including structured training, high-sensitivity assays, RNA-based methods, and artificial intelligence-assisted pathology—are summarized. Finally, we reconsider the therapeutic implications of ADCs, with the question of whether the benefit parallels HER2 expression or extends into HER2-null disease. HER2 exemplifies how biomarker interpretation evolves with drug development. As new ADCs target additional antigens, pathologists must balance trial-driven categories with biologic reproducibility to ensure diagnostics remain aligned with therapeutic advances.

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Mechanisms of Resistance and Synergy: The Role of Tumor Microenvironment in HER2-Low Breast Cancer Therapy
Youssef Basem, Alamer Ata, Abanoub Sherif, Shaimaa Abdel-Ghany, Borros Arneth, Hussein Sabit
Pharmaceuticals.2026; 19(4): 541. CrossRef

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Silence of Transmembrane Channel-Like 5 Inhibits Cell Proliferation, Migration, and Invasion While Promoting Apoptosis Via Deactivating the AKT Pathway in Breast Cancer: Jinnan Wan, Yang Li, Zhimin Liu; Received July 30, 2025 Accepted December 7, 2025 Published online December 9, 2025; DOI: https://doi.org/10.4143/crt.2025.805 [Accepted]

Abstract PDF: Purpose
Transmembrane channel-like 5 (TMC5) plays a tumor-promoting role in the progression of various tumors. However, its effect on regulating breast cancer cell function remains scarce. The current study aimed to evaluate the effect of TMC5 silence on the proliferation, apoptosis, migration, and invasion of breast cancer cell lines.
Materials and Methods
TMC5-specific small interfering RNA (siTMC5) and siNC were transfected into MDA-MB-231 and MCF-7 cell lines; subsequently, the 740Y-P was co-cultured. Then, the proliferation, apoptosis, migration, invasion, and p-AKT expression were determined.
Results
In MDA-MB-231 and MCF-7 cell lines, silence of TMC5 could reduce the proliferation rate at 48 hours (h) and 72 h, migration rate, and invasion rate, while elevate the apoptosis rate. Besides, silence of TMC5 could decrease the p-AKT/AKT expression. The combination of 740Y-P with the silence of TMC5 could reversely increase the proliferation rate at 48h and 72h, migration rate, and invasion rate compared with the silence of TMC5 only. The apoptosis rate showed the opposite trend.
Conclusion
The silence of TMC5 could inhibit the proliferation, migration, and invasion while promoting the apoptosis of breast cancer, while more in vivo validation is needed to explore its potential to be a treatment target for patients with breast cancer.

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Dual-Functional PTX@Fe₃O₄ Nanobubbles: A Novel Theranostic Platform for Enhanced Ultrasound Imaging and Controlled Drug Delivery in Breast Cancer: Weiyang Lv, Xiaomei Ning, Chunxin Huang, Xing Li, Lianjie Bai, Xiaotong Wang, Zihan Wang, Yunna Song, Huilin Liu; Received September 26, 2025 Accepted November 16, 2025 Published online November 17, 2025; DOI: https://doi.org/10.4143/crt.2025.1055 [Accepted]

Abstract PDF: Purpose
This study aimed to develop a novel theranostic nanoplatform that integrates ultrasound imaging and controlled drug delivery for the treatment of breast cancer.
Methods
PTX@Fe₃O₄ nanobubbles (NBs) were synthesised via microfluidics. Characterisation included transmission electron microscopy, dynamic light scattering, drug release kinetics, phantom imaging and biocompatibility assays in vitro and in mice.
Results
The NBs exhibited uniform size (178 ± 12 nm), high drug loading (8.3%) and pH/ultrasound-responsive release (68.2% at pH 5.5+US). Ultrasound signal enhancement correlated linearly with concentration (R² = 0.988), with imaging duration three times longer than SonoVue. The system exhibited minimal haemolysis (<2%) and low cytotoxicity and induced S-phase arrest (68.2%) in MCF-7 cells. No significant toxicity was observed in mice at 10 mg Fe/kg.
Conclusion
PTX@Fe₃O₄ NBs represent a promising, biocompatible theranostic platform for image-guided breast cancer therapy.

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The Impact of Post Mastectomy Radiotherapy on T1-2N0-1 Male Breast Cancer and establishment of an artificial neural network predicting model: Population-Based Study: Kaiyan Huang, Yushuai Yu, Xiaofen Li, Yushan Liu, Kailong Huang, Xin Wang, Jie Zhang; Received May 14, 2025 Accepted November 4, 2025 Published online November 5, 2025; DOI: https://doi.org/10.4143/crt.2025.518 [Accepted]

Abstract PDF

Purpose
The objective of this study was to analyze the impact of post-mastectomy radiotherapy (PMRT) in male breast cancer (MBC) patients and develop an artificial neural network (ANN) model to identify a potential PMRT benefit population.
Materials and Methods
Data from a total of 2,247 MBC patients with T1-2N0-1M0 who underwent total mastectomy between 1998 and 2016 were enrolled from the SEER database. Propensity score matching was used to reduce covariate imbalances. Cox regression analysis was conducted to compare overall survival (OS) between the PMRT and no-PMRT groups. The hypothesis was that patients who had undergone PMRT and lived longer than the median OS of the no-PMRT group could benefit from PMRT. An ANN model was then developed to predict PMRT benefit population.
Results
Multivariate Cox regression analysis demonstrated better OS in the PMRT group compared to the no-PMRT group of matched patients. This survival benefit was particularly significant in patients with grade III or T2N0 and T2N1 disease, while no significant difference was observed in patients with grade I/II or T1N0 and T1N1 disease. An ANN model was established to predict PMRT benefit population based on patients with T2N0/T2N1. The optimal cut-off value for the model predicted probability was 0.51. Survival curves indicated that a score of 0.51 could accurately distinguish potential PMRT benefit population.
Conclusion
For MBC patients with T2N0, T2N1, and grade III, PMRT would improve survival. The ANN model would be used to identify patients who are likely to benefit from PMRT and aid in clinical decision-making.

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Case Report: long-term survival of a male patient with breast cancer complicated by lung adenocarcinoma treated with individualized therapy
Yadong Liu, Xuejuan Duan, Zhenru Zheng, Gang Cheng, Xianbo Zhang, Jing Zhao
Frontiers in Oncology.2026;[Epub] CrossRef

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Effects of Exercise Interventions on Breast Cancer Patients During Adjuvant Therapy: A Systematic Review and Meta-Analysis: Zhiyuan Sun, Tengteng Han, Lianshi Feng, Dewei Mao, Can Zhao, Jie Han, Qinghui Shang; Received July 22, 2025 Accepted September 28, 2025 Published online October 2, 2025; DOI: https://doi.org/10.4143/crt.2025.762 [Accepted]

Abstract PDF: Purpose
Exercise can enhance the therapeutic effects of adjuvant medications, improve both physiological and psychological functions, and increase physical fitness among breast cancer patients receiving adjuvant therapy. This systematic review and meta-analysis examined the latest research on the effects of exercise interventions in this population. Furthermore, subgroup analyses were performed based on exercise type, intensity, frequency, duration and Types of adjuvant therapy.
Materials and Methods
The PubMed, Embase, CINAHL, and CENTRAL databases were systematically searched from inception to April 2024 to identify randomized controlled trials (RCTs) examining the use of exercise interventions among breast cancer patients receiving adjuvant therapy. The data extracted from the included studies were analyzed via RevMan 5.4.
Results
A total of 34 studies involving 2,696 participants were included, with 1,369 in the intervention group and 1,327 in the control group, and a mean age ranging from 40 to 60 years. Compared to the control group, exercise interventions improved fatigue, muscular strength, cardiorespiratory fitness, inflammation, and quality of life in breast cancer patients (fatigue: SMD=–0.29, 95% CI (–0.50, 0.09), p=0.005; upper limb strength: SMD=0.50, 95% CI (0.33, 0.68), p<0.00001, lower limb strength: SMD=0.37, 95% CI (0.22, 0.52), p<0.0001; cardiorespiratory fitness: SMD =0.51, 95% CI (0.26,0.75), p<0. 0001; inflammation: SMD =–0.36, 95% CI (–0.66, –0.06), p=0.02; quality of life: SMD=0.21, 95% CI (0.11, 0.31), p< 0.0001). Moderate effect sizes were observed for the alleviation of anxiety and depressive symptoms, although these results did not reach statistical significance (depression: SMD=–0.13, 95% CI (–0.28, 0.02), p=0.08; anxiety: SMD=–0.81, 95% CI (–1.65, 0.03), p=0.06). This meta-analysis was registered in Prospero, the international register of systematic reviews, with registration number: CRD42024553589.
Conclusion
Exercise during adjuvant therapy can reduce the side effects of adjuvant medications, improve both physiological and psychological functions, and enhance physical fitness among patients with breast cancer.

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IFITM1 Influences Natural Killer Cell–Mediated Cytotoxicity by Modulation of HLA Class I Expression in Triple-Negative Breast Cancer Cells: Heejin Lee, Chanyeon Park, Keunsoo Kang, Soon Auck Hong, Gyungmin Cho, Inyoung Cheon, Young-Ho Ahn, Jung-Sook Yoon, Yoon Ho Ko, Hye Sung Won; Received June 30, 2025 Accepted September 23, 2025 Published online September 25, 2025; DOI: https://doi.org/10.4143/crt.2025.444 [Epub ahead of print]

Abstract PDF Supplementary Material: Purpose
Interferon-induced transmembrane protein 1 (IFITM1) is associated with a poor prognosis in triple-negative breast cancer (TNBC); however, the mechanisms by which IFITM1 contributes to oncogenesis in TNBC are unclear.
Materials and Methods
We established two stable cell lines: IFITM1-overexpressing cell line (MB-231-IFITM1-OE) and IFITM1 knockdown cell line (BT-20-IFITM1-KD). The transcriptional activity of β-catenin and the cytotoxic activity of natural killer (NK) cells were evaluated using the luciferase assay and the lactate dehydrogenase cytotoxicity assay. The expression of IFITM1, β-catenin, and human leukocyte antigen (HLA) class I was assessed by immunohistochemistry in patients with TNBC.
Results
Knockdown of IFITM1 in BT-20 cells reduced cell proliferation and ectopically expressed IFITM1 in MB-231 cells increased cell proliferation. RNA sequencing analysis revealed that IFITM1 expression positively correlated with the Wnt/β-catenin signaling pathway and NK cell–mediated cytotoxicity. MB-231-IFITM1-OE cells showed increased β-catenin transcriptional activity and NK cell cytotoxic activity compared with controls, while transient knockdown of IFITM1 in MB-231-IFITM1-OE cells led to a decrease in β-catenin transcriptional activity and NK cell cytotoxic activity. MB-231-IFITM1-OE cells exhibited decreased HLA class I expression, which may have contributed to their increased susceptibility to NK cell–mediated lysis. β-catenin or JAK inhibitor reduced NK cell–mediated cytotoxicity via upregulation of HLA class I. Patients with IFITM1 overexpression showed a trend toward increased β-catenin positivity and HLA class I negativity.
Conclusion
IFITM1 overexpression was associated with Wnt/β-catenin signaling and NK cell–mediated cytotoxicity via downregulation of HLA class I in TNBC cells, suggesting that IFITM1 might have immunoregulatory effects on the tumor microenvironment.

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LRRC15 Promotes the Development of Breast Cancer by Regulating Autophagy through the PI3K/AKT/mTOR Signaling Pathway: Xinru Fan, Liu Gao, Zheng Zhang, Xu Jiang, Xiawei Wang, Jiayu Shi, Yu Ling, Rundong Yan, Jiani Shi, Li Yu; Received May 20, 2025 Accepted September 21, 2025 Published online September 24, 2025; DOI: https://doi.org/10.4143/crt.2025.543 [Accepted]

Abstract PDF: Purpose
Leucine-rich repeats (LRR) play important roles in tumorigenesis and may serve as novel biomarkers for cancer therapy. The expression of leucine-rich repeat-containing protein 15 (LRRC15) is increased in several cancers. However, it is still unknown whether LRRC15 is involved in breast cancer and autophagy.
Materials and Methods
This study conducted bioinformatic analysis on LRRC15 expression and prognosis in breast cancer. Clinical samples were collected and subjected to immunohistochemistry and qRT-PCR to analyze LRRC15 expression in tissues and serum. Clonal formation, MTT, wound healing, and Transwell assays were used to examined breast cancer cell proliferation, migration, and invasion. Western blotting detected autophagy-related and PI3K/AKT/mTOR signaling pathway proteins.
Results
Patients with breast cancer having elevated expression of LRRC15 have a markedly worse prognosis compared with those having lower levels. Furthermore, LRRC15 expression was strongly correlated with tumor aggressiveness and poor differentiation in breast cancer cell lines. Functionally, LRRC15 drives cancer cell proliferation, migration, and invasion. LRRC15 inhibited autophagy in breast cancer cells, thus modulating their proliferative capacity. Mechanistically, LRRC15 exerted these effects by activating the PI3K/AKT/mTOR signaling cascade.
Conclusion
LRRC15 regulates autophagy-induced proliferation and other biological activities of breast cancer cells through the PI3K/AKT/mTOR signaling pathway.

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Noninvasive Assessment of Ki-67 Expression in Breast Cancer Using Ultrasound Radiomics: A Multi-Institutional Study: Sijie Mo, Zhibin Huang, Jing Zheng, Huaiyu Wu, Shuzhen Tang, Mengyun Wang, Jinfeng Xu, Hongtian Tian, Xiaoli Huang, Fajin Dong; Received May 30, 2025 Accepted September 2, 2025 Published online September 5, 2025; DOI: https://doi.org/10.4143/crt.2025.581 [Epub ahead of print]

Abstract PDF Supplementary Material PubReader ePub

Purpose
This study aimed to develop and rigorously evaluate machine learning models using ultrasound (US) breast cancer (BC) images to predict Ki-67 expression. Additionally, the study sought to identify independent factors influencing Ki-67 expression, with further test conducted through external datasets.
Materials and Methods
This study analyzed US images of BC from 347 patients (training set: n=230; external test set: n=117) from Shenzhen People’s Hospital and Guangxi Academy of Medical Sciences. Radiomic features were extracted using manual region-of-interest delineation and the Pyradiomics package. Feature selection was performed using Least Absolute Shrinkage and Selection Operator (LASSO) and decision tree analysis, resulting in 16 features. Machine learning models—logistic regression (LR), support vector machine (SVM), and multilayer perceptron (MLP)—were developed, and their performance was assessed using the area under the receiver operating characteristic curve, accuracy, sensitivity, specificity, and decision curve analysis. Statistical analysis included univariate and multivariate logistic regression.
Results
Three machine learning models (LR, SVM, and MLP) were developed to predict Ki-67 expression from US images. The LR model demonstrated the best diagnostic performance, with an area under the curve of 0.800 in external test set. Key predictors of Ki-67 expression included ill-defined maximum mass diameter and human epidermal growth factor receptor 2 expression, along with other significant clinical variables.
Conclusion
This dual-center study demonstrates the potential of radiomics models based on US BC images to predict Ki-67 expression accurately. As a non-invasive diagnostic tool, this approach offers valuable support for clinical decision-making and personalized treatment planning in BC patients.

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Utility of Ki-67 index combined with alpha-fetoprotein and lactate dehydrogenase in distinguishing mature from immature ovarian teratomas in children
Xiazhe Li, Zhiyong Zhong, Yanwei Qi, Yingxin Gong
Frontiers in Neurology.2026;[Epub] CrossRef

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Long-term Prognostic Value and Analytical Parameters of the Next-Generation Sequencing–Based Multigene Assay in Hormone Receptor–Positive, HER2-Negative Breast Cancer: Hyunji Kim, Jiwon Koh, Hyunwoo Lee, Gyungyub Gong, Sujin Oh, Jiyoung Lee, Ho Eun Chang, Yunhee Choi, Eunhye Kang, Jai Min Ryu, Dong Seung Shin, Sae Byul Lee, Hee Jin Lee, Hong-Kyu Kim, Hee-Chul Shin, Wonshik Han, Han-Byoel Lee, Kyoung Un Park; Received July 7, 2025 Accepted August 29, 2025 Published online September 1, 2025; DOI: https://doi.org/10.4143/crt.2025.701 [Epub ahead of print]

Abstract PDF Supplementary Material PubReader ePub: Purpose
In hormone receptor (HR)–positive, human epidermal growth factor receptor 2 (HER2)–negative early breast cancer, gene expression testing facilitates treatment decisions. A next-generation sequencing (NGS)–based assay was developed to address test decentralization and underrepresentation of younger/premenopausal patients. We aimed to validate the long-term prognostic value of the NGS-based assay and analyze its quality control (QC) parameters.
Materials and Methods
We analyzed samples from 265 patients with breast cancer with at least 10 years of follow-up. We evaluated the long-term prognostic ability of the NGS-based assay according to the risk groups for distant recurrence, as determined by the Decision Index, and the performance of the QC parameters used for the experimental process.
Results
Among 265 participants, 60.4% were ≤ 50 years old, and 39 (14.7%) experienced distant recurrence within 10 years. In the Decision Index–stratified low- and high-risk groups (n=186, 70.2% and n=79, 29.8%), 10-year distant metastasis–free survival rates were 96.1% (95% confidence interval [CI], 92.1 to 98.1) and 79.3% (95% CI, 68.4 to 86.8), respectively. In patients aged ≤ 50 years, the high-risk group had a hazard ratio of 5.89 (95% CI, 2.84 to 12.20). Analyses including 106 samples that failed the stringent QC criteria showed inferior prognostic value, wherein DV200 and cDNA concentrations were the most crucial parameters.
Conclusion
We validated the prognostic ability of an NGS-based assay to stratify HR-positive/HER2-negative breast cancers and predict the risk of distant recurrence, and confirmed the requirement for stringent QC criteria to ensure its prognostic ability.

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Nomograms Integrating Body Composition Metrics Predict Total Pathologic Complete Response after Neoadjuvant Systemic Therapy for Breast Cancer: Jingjing Ding, Yichun Gong, Jue Wang, Yuanyuan Wang, Hao Yao, Xingye Sheng, Mingyu Wang, Danni Shen, Junhan Li, Xiaoming Zha, Lu Xu; Received April 28, 2025 Accepted August 17, 2025 Published online August 18, 2025; DOI: https://doi.org/10.4143/crt.2025.456 [Epub ahead of print]

Abstract PDF PubReader ePub: Purpose
Neoadjuvant systemic therapy (NST) is a systemic treatment for locally advanced or initially unresectable breast cancer before surgery. Patients who achieved total pathologic complete response (tpCR) after NST exhibited significantly better overall prognosis than patients with non–pathological complete response.
Materials and Methods
This study collected baseline indicators, body composition indicators, and tpCR results of breast cancer patients at the First Affiliated Hospital of Nanjing Medical University. Patients were divided into training set and validation set in a ratio of 7:3. Univariable and multivariable logistic regression analyses were performed, and the probability of tpCR was predicted by constructing nomograms based on the results of the multivariable logistic regression analysis.
Results
The study included 500 patients between 2014 and 2022 with breast cancer who underwent NST. The training set and validation set consist of 350 and 150 patients, respectively. Patients with progesterone receptor–negative status (p < 0.001), human epidermal growth factor receptor 2–positive status (p < 0.001), large body surface area (p=0.091), low skeletal muscle index (p=0.008), and high skeletal muscle density (p=0.004) were more likely to achieve tpCR. Patients with American Joint Committee on Cancer (AJCC) T-stage 4 (p=0.126), AJCC N-stage 1 (p=0.026) were less likely to achieve tpCR.
Conclusion
Existing tpCR prediction models mostly focus on tumor biological characteristics and ignore the effect of body compositions. This study constructed a nomogram to predict tpCR in patients with breast cancer undergoing NST based on baseline and body composition indicators. This nomogram can help assess efficacy and optimize treatment strategies, thus improving the overall prognosis of patients.

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Proteomic Analysis Identifies Association of Periostin, a Matricellular Protein, with High Tumor Stroma and Immune Exclusion in Triple-Negative Breast Cancer: Yeonjin Jeon, GunHee Lee, Byung-Kwan Jeong, Yoon Young Kim, JiSun Kim, Jae Ho Jeong, Kyunggon Kim, Hee Jin Lee; Received February 6, 2025 Accepted July 25, 2025 Published online July 28, 2025; DOI: https://doi.org/10.4143/crt.2025.145 [Epub ahead of print]

Abstract PDF Supplementary Material PubReader ePub

Purpose
Immune-excluded/desert tumors show reduced responsiveness to immunotherapy compared to inflamed tumors. The tumor stroma contributes to immune evasion. This study aimed to identify proteins overexpressed in tumors with high tumor stroma among immune excluded triple-negative breast cancer (TNBC) to better understand the mechanisms of immune exclusion.
Materials and Methods
Proteomic analysis was conducted on formalin-fixed, paraffin-embedded samples from 403 cases of TNBC. We compared protein expression between stroma-high versus stroma-low within the immune-excluded subtype. We investigated the correlations between the identified protein expression and other clinicopathologic features. Immunohistochemical (IHC) staining and single-cell analysis were conducted, along with survival analysis.
Results
Among the 247 eligible cases, 81 (32.8%) were classified as immune-excluded and 166 (67.2%) as inflamed. Within the excluded subtype, periostin was the only extracellular matrix-related protein significantly overexpressed in stroma-high cases. Periostin expression demonstrated a positive correlation with the amount of stroma (r=0.51, p < 0.001) and a negative correlation with tumor-infiltrating lymphocytes (TILs) (r=−0.30, p < 0.001). Periostin expression in the tumor stroma was confirmed by IHC. Single-cell analysis demonstrated that periostin originated from cancer-associated fibroblasts (CAFs). High periostin levels correlated with poorer recurrence-free survival (hazard ratio, 1.422; p=0.005).
Conclusion
Periostin is overexpressed in stroma-rich, immune-excluded TNBC and is derived from CAFs. Its expression is associated with reduced TILs and poor prognosis. The development of targeted agents against periostin-positive CAFs may help overcome immune evasion and improve the effectiveness of immunotherapy in TNBC.

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POSTN+ cancer-associated fibroblasts promote bladder cancer progression via angiogenesis and immune modulation: an analysis based on single-cell Transcriptomics
Qun Zhang, Bo Zhang, Jirui Niu, Shiheng Sun
Integrative Biology.2026;[Epub] CrossRef

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1 Crossref

Keratin 6A Overexpression in the Lymphovascular Invasion–Associated Tumor Subgroup Promotes Progression of Triple-Negative Breast Cancer: Wei Luo, Yiping Zou, Yantao Jiang, Xi Ma, Shuyue Guo, Yao Wang, Yuxiao Liu, Linyue Hai, Wenbin Jia, Wenbo Liu, Ran Meng, Xuchen Cao, Xianhui Ruan, Yue Yu; Received April 17, 2025 Accepted July 11, 2025 Published online July 14, 2025; DOI: https://doi.org/10.4143/crt.2025.423 [Epub ahead of print]

Abstract PDF Supplementary Material PubReader ePub

Purpose
Lymphovascular invasion (LVI) is a strong predictor of poor prognosis in triple-negative breast cancer (TNBC), yet its molecular basis remains unclear. This study investigates epithelial regulators associated with LVI and their functional roles in TNBC progression.
Materials and Methods
We utilized single-cell sequencing data to further characterize epithelial cell populations in TNBC, identifying dominant epithelial clusters in LVI-positive TNBC tissues. The prognostic significance of dominant epithelial marker genes was explored through transcriptomic analysis and immunohistochemical staining of patient samples from our center. Additionally, the effects of the marker gene on TNBC cell invasion and metastasis were validated in vitro and in vivo.
Results
Single-cell data analysis revealed nine distinct epithelial cell clusters within TNBC tissues. Among these, cluster 4 was identified as the dominant epithelial subpopulation in LVI-positive TNBC, marked by the prognostic gene KRT6A. Multiple datasets confirmed KRT6A as a crucial prognostic marker in TNBC. Functional assays, including Cell Counting Kit-8, wound healing, transwell assays, and animal experiments, demonstrated that KRT6A knockdown significantly impaired the proliferation, invasion, and metastatic potential of TNBC cells. Mechanistically, KRT6A promoted epithelial-mesenchymal transition (EMT) and activated Wnt/β-catenin signaling by stabilizing β-catenin through glycogen synthase kinase-3β phosphorylation.
Conclusion
KRT6A promotes EMT and metastasis in TNBC via Wnt/β-catenin signaling, contributing to LVI and chemoresistance. It may serve as a prognostic biomarker and therapeutic target in TNBC.

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Targeting keratin 6 A overcomes gemcitabine resistance by restoring equilibrative nucleoside transporter 1 and TAM-mediated metabolic compensation in pancreatic cancer
Junfeng Zhang, Xianxing Wang, Silue Zeng, Bo Tang, Xinyi Yang, Shaowen Xie, Haihan Sun, Ru Wang, Renpei Xia, Jinghe Li, Huaizhi Wang, Zhitian Shi, Jianyou Gu, Dong Wei
Drug Resistance Updates.2026; 87: 101404. CrossRef
Signaling Networks Regulating Metastatic Progression in Triple-Negative Breast Cancer
Zuzanna Senkowska, Katarzyna Owczarek, Karolina Niewinna, Urszula Lewandowska
Cells.2026; 15(9): 809. CrossRef

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HER3 Expression and PIK3CA Mutational Status Predict Pathological Response of Neoadjuvant Therapy in HER2-Positive Breast Cancer Patients: Xi Xia, Zhiqiang Zong, Jian Shen, Lingling Zhou, Yang Lei, Jia Li, Lu Zheng, Fanfan Li, Hua Wang; Received March 4, 2025 Accepted July 1, 2025 Published online July 2, 2025; DOI: https://doi.org/10.4143/crt.2025.242 [Epub ahead of print]

Abstract PDF PubReader ePub

Purpose
The main purpose of this study is to explore the predictive value of human epidermal growth factor receptor 3 (HER3) expression level and PIK3CA mutation for the efficacy of neoadjuvant therapy in human epidermal growth factor receptor 2 (HER2)–positive breast cancer patients.
Materials and Methods
The clinicopathological data of HER2-positive non-specific invasive breast cancer patients who received neoadjuvant treatment in the Second Affiliated Hospital of Anhui Medical University from June 2017 to June 2024 were retrospectively analyzed. The correlation between HER3 expression level detected by immunohistochemistry and PIK3CA gene mutation detected by amplification refractory mutation system–polymerase chain reaction and pathological complete response (pCR) was analyzed.
Results
Among 51 patients, 29 (56.9%) had positive HER3 expression, 15 (29.4%) had PIK3CA mutation, and 19 (37.3%) had pCR. The expression level of HER3 was correlated with the pCR rate (χ²=7.905, p=0.019). The PIK3CA mutation status was not correlated with the pCR rate (χ²=0.140, p=0.708). The HER3 expression level combined with PIK3CA mutation status affected the pCR rate (p=0.036). Multivariable regression further identified HER3 positivity as an independent negative predictor of pCR (odds ratio, 0.08; 95% confidence interval, 0.01 to 0.50; p=0.008), underscoring its role in therapeutic resistance.
Conclusion
HER3 expression may serve as a critical biomarker for guiding therapeutic strategies in HER2-positive breast cancer patients. The combinatorial effect of HER3 overexpression and PIK3CA mutations may exacerbate therapeutic resistance, while dual-targeted strategies against the HER3/phosphoinositide 3-kinase pathway could potentially improve clinical outcomes in treatment-resistant populations.

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AGTPBP1 Promotes Breast Cancer Progression via the EVPL/ERK Signaling Axis
Hudeer Song, Hongxia Li, Yanchao Bian, Jingyuan Song, Chenxi Yang, Houke Lu, Yuqi Zhang, Pengfei Li, Rui Xiao
Experimental Cell Research.2026; : 115001. CrossRef

1,386 View
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1 Crossref

Breast cancer

Radiation-Associated Heart Disease in Korean Women after Radiotherapy for Breast Cancer: Insights from the National Health Insurance Service Database: Jun-Hyuk Lee, Jimin Park, Tae Hyung Kim; Cancer Res Treat. 2026;58(2):534-543. Published online June 11, 2025; DOI: https://doi.org/10.4143/crt.2025.233

Abstract PDF Supplementary Material PubReader ePub: Purpose
This study investigated the risk of radiation-associated heart disease (RAHD) in Korean women treated with radiotherapy (RT) for breast cancer (BC) using data from the National Health Insurance Service database.
Materials and Methods
A retrospective cohort analysis was conducted on 65,188 patients with BC treated with RT between 2009 and 2014 and 325,940 controls without BC or prior coronary artery disease (CAD), with 1:5 exact matching by age, type 2 diabetes mellitus, hypertension, and dyslipidemia status. CAD encompassed both incident events and fatal events. Competing risk analysis was conducted to estimate subdistribution hazard ratio (HR) with 95% confidence interval (CI) for CAD, setting mortality from non-CAD causes as a competing risk.
Results
During the mean 9.9 years of follow-up period, 3,852 (1.0%) CAD and 20,999 (5.4%) death from non-CAD causes were reported. Compared to controls, participants with BC who received RT had a significantly lower risk of CAD incidence. HR (95% CI) for CAD in the BC with RT group was 0.66 (0.60-0.73, p < 0.001). On the other hand, HR (95% CI) for mortality from non-CAD causes was 3.57 (3.48-3.67, p < 0.001).
Conclusion
In this large population-based cohort study, breast cancer patients who received RT did not show an increased incidence of CAD compared with the general population without breast cancer. Individual-level dosimetric data and longer follow-up are needed to clarify the independent risk.

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Secondary Cancer Risk in Breast Cancer with and without Radiotherapy: The Observational Health Data Sciences and Informatics (OHDSI) Cohort Study: Seok Kim, Dachung Boo, Sooyoung Yoo, Borham Kim, Kyubo Kim, Kwangsoo Kim, Eunhye Song, Junmo Kim, Hyun Gee Ryoo, Jin Chul Paeng, In Young Choi, SooJeong Ko, Ie Ryung Yoo, Rae Woong Park, Ho-Young Lee; Cancer Res Treat. 2026;58(2):481-491. Published online June 5, 2025; DOI: https://doi.org/10.4143/crt.2024.968

Abstract PDF Supplementary Material PubReader ePub: Purpose
Radiotherapy is used to reduce the risk of breast cancer recurrence after surgery, but it is a potential cause of secondary cancer. We validated the risk of secondary cancer in primary breast cancer who received radiotherapy compared with those who did not from a matched cohort using a large-scale observational study of the Observational Health Data Sciences and Informatics (OHDSI) data network.
Materials and Methods
A retrospective comparative cohort study using propensity score-matched cohorts was performed using two Observational Medical Outcome Partnership common data model databases, from tertiary general hospitals in South Korea. Among female patients who underwent surgery after the diagnosis of breast cancer, the risk of secondary primary malignant occurrence after 1:1 matching was analyzed.
Results
Among 27,078 patients with breast cancer, there was no significant difference in the risk of secondary cancer following radiotherapy in 4,426 patients after 1:1 propensity-score matching. Further, there were no significant differences in the sensitivity analysis according to age, latency period, and number of radiation treatments.
Conclusion
There was no difference in the risk of secondary cancer in the patients diagnosed with breast cancer depending on whether or not radiotherapy was performed after surgery. In the future, it is necessary to analyze including data generated during cancer treatment.

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Sex Disparities in Breast Cancer Survival According to Clinical Treatment Score Post-5 Years (CTS5) Risk Stratification: Ke Liu, Zhen-Zhen Lu, Zhen-Yu He, San-Gang Wu; Cancer Res Treat. 2026;58(2):525-533. Published online May 27, 2025; DOI: https://doi.org/10.4143/crt.2025.361

Abstract PDF PubReader ePub: Purpose
The role of the Clinical Treatment Score post-5 years (CTS5) in male breast cancer (MBC) remains unclear. This study aimed to investigate the characteristics and prognosis of CTS5 between MBC and female breast cancer (FBC).
Materials and Methods
Patients diagnosed with human epidermal growth factor receptor 2–negative/estrogen receptor–positive breast cancer between 2010 and 2015 were identified from the Surveillance, Epidemiology, and End Results (SEER) database. The chi-square test, Kaplan-Meier analysis, and multivariate Cox proportional hazard model were used for statistical analysis.
Results
This study included 169,869 patients, comprising 168,422 (99.1%) FBC and 1,447 (0.9%) MBC patients. More MBC patients had intermediate risk (IR)/high risk (HR) disease compared to FBC patients (17.7% vs. 8.7%, p < 0.001). MBC patients had an inferior overall survival (OS) but similar breast cancer-specific survival compared to those with FBC. Sensitivity analyses showed that sex was an independent prognostic factor associated with OS but not breast cancer-specific survival (BCSS) in both the low-risk (LR) and IR/HR cohorts. Those with MBC exhibited significantly worse OS (p < 0.001) than FBC patients in both cohorts. In MBC patients, those with IR/HR disease had significantly worse OS (p < 0.001) and BCSS (p < 0.001) compared to those with LR disease. For FBC patients, the IR/HR group had also significantly worse OS (p < 0.001) and BCSS (p < 0.001) compared to the LR group.
Conclusion
Our findings highlight critical differences in clinical characteristics, treatment patterns, and outcomes between MBC and FBC, suggesting the need for sex-tailored approaches in breast cancer management.

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Comparative Study of Mastectomy Using Conventional Techniques, Multiport and Single-Port Robotic Surgical Systems: Jeea Lee, Jieon Go, Suk Jun Lee, Yonghan Kwon, Nam Hee Kim, Jee Ye Kim, Hyung Seok Park; Cancer Res Treat. 2026;58(2):492-500. Published online May 7, 2025; DOI: https://doi.org/10.4143/crt.2025.115

Abstract PDF Supplementary Material PubReader ePub

Purpose
Oncologic and surgical outcomes of robot-assisted nipple-sparing mastectomy (RNSM) compared to conventional nipple-sparing mastectomy (CNSM) is under investigation. This study compared the clinical outcomes of recurrence-free survival and postoperative complication after RNSM and CNSM.
Materials and Methods
We retrospectively reviewed data of 401 patients who underwent da Vinci Si/Xi/SP-assisted RNSM or CNSM with immediate reconstruction between November 2016 and November 2020 at a single institute. Oncological outcomes were collected until March 2022. Primary endpoints were long-term outcomes, such as local recurrence, distant metastasis, disease-free survival, overall survival, and postoperative complications, while secondary endpoints were pathology results, and oncological outcomes.
Results
Patients underwent RNSM (n=162) or CNSM (n=239). Of RNSM cases, 9 (5.6%) were performed using the da Vinci Si System, 96 (59.3%) using the da Vinci Xi System, and 57 (35.2%) using the da Vinci SP System. No significant difference in recurrence-free survival was found between the RNSM and CNSM group, and both groups had a median follow-up of 37 months. The recurrence rate in RNSM patients after a median follow-up of 24.5 months was 3.8%, compared with 5.9% in CNSM patients after a median follow-up of 42 months. No difference in recurrence was seen among RNSM patients with respect to surgical systems (multiport vs. SP, p =0.136). In addition, grade III postoperative complication rate was lower in patients with RNSM than in those with CNSM. Transfusion was only applied in 6.2% of patients.
Conclusion
Robot-assisted surgical systems can be safely used to perform nipple-sparing mastectomy in patients with early breast cancer.

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Feasibility and outcomes of single-incision robotic nipple-sparing mastectomy: a systematic review and meta-analysis
Hasan Asfour, Hussein Lubbad, Ewa Anna Sobczak, Walid Sasi
Journal of Robotic Surgery.2026;[Epub] CrossRef
Single-port robotic nipple-sparing mastectomy: a systematic review and single-arm meta-analysis of safety and process outcomes
Ronghao Ouyang, Ximeng Jia, Yutong Liang, Benjie Li, Mengzhe Qing, Jintian Hu
Journal of Robotic Surgery.2025;[Epub] CrossRef

2,105 View
188 Download
2 Web of Science
2 Crossref

Safety and Effectiveness of Eribulin in Patients with Advanced or Metastatic Breast Cancer Previously Treated with Anthracyclines and Taxanes in Real-World Clinical Practice: A 6-Year Post-marketing Surveillance Study in South Korea: Yee Soo Chae, Kyung A Kwon, Moon Hee Lee, Mi Sun Ahn, Kyung-Hun Lee, Su-Jin Koh, Joohyuk Sohn, Keon Uk Park, Min Young Kim, Youngji Pyo, Bo Young Kim, Kyung Hae Jung; Cancer Res Treat. 2026;58(2):513-524. Published online April 28, 2025; DOI: https://doi.org/10.4143/crt.2024.1142

Abstract PDF PubReader ePub: Purpose
This 6-year post-marketing surveillance (PMS) study was conducted in South Korea to evaluate the real-world safety and effectiveness of eribulin in patients with advanced or metastatic breast cancer previously treated with anthracyclines and taxanes.
Materials and Methods
During the study period (17 August 2012 to 16 August 2018), case-report files (CRFs) of patients receiving eribulin were collected. The main study endpoint was to assess the safety of eribulin. Evaluation of the effectiveness of eribulin was an exploratory endpoint. Patients were followed for 1 year after eribulin initiation.
Results
CRFs were collected from 64 investigators at 64 sites for 1,079 patients. The safety analysis set (SAS) included 1,001 eribulin recipients; effectiveness was assessed in 244 patients. In the SAS, patients were predominantly female (99.6%), with a median age of 53.0 years, and diagnosed with metastatic breast cancer (92.0%). Eribulin was administered as a median 4th line chemotherapy. A total of 2,124 treatment-emergent adverse events (TEAEs) were reported in 661 patients (66.0%). Neutropenia was the most common TEAE (32.5% of patients), occurring at a median of 9-11 days from initial eribulin administration. Overall response and disease control rates were 31.7% and 95.6%, respectively, and the median duration of eribulin use (time to treatment failure) was 3.0 months.
Conclusion
This large real-world PMS analysis in patients with advanced or metastatic breast cancer demonstrated the effectiveness of eribulin and found no new safety concerns relative to safety information from prior clinical and real-world studies, and approvals in South Korea and other countries.

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Adjuvant Chemotherapy in Breast Cancer after Neoadjuvant Therapy: Essential or Optional?: Di Zhang, Luo Yang, Yuan Zheng, Qi Zhou; Cancer Res Treat. 2026;58(1):208-220. Published online April 24, 2025; DOI: https://doi.org/10.4143/crt.2024.1254

Abstract PDF Supplementary Material PubReader ePub: Purpose
This study aimed to evaluate the impact of postoperative adjuvant chemotherapy (AC) on survival outcomes in breast cancer (BC) patients who have already undergone neoadjuvant chemotherapy (NAC) followed by surgery.
Materials and Methods
Data from a population-based cohort (2010-2020) were analyzed for BC patients treated with NAC and surgery. Univariate and multivariate Cox regression identified prognostic factors for overall survival (OS), and a nomogram was developed and validated. Personalized scores from the nomogram were used for risk stratification to assess the effect of postoperative AC.
Results
A total of 15,921 BC patients were analyzed, with 11,144 in the training cohort and 4,777 in the validation cohort. The key prognostic indicators for OS included age, race, marital status, histological grade, BC subtype, T category, N category, type of surgery, and response to NAC (all p < 0.05). The nomogram effectively predicted individualized OS rates and stratified patients into various risk categories. Postoperative AC was found to significantly enhance OS in the high-risk subgroup (p=0.011 in the training cohort, p=0.012 in the overall population). However, for the low-risk subgroup, there was no significant survival benefit from postoperative AC (p=0.130 for the training cohort, p=0.588 for the overall population), suggesting that some patients might safely forgo unnecessary postoperative AC.
Conclusion
This study efficiently differentiates between varying levels of risk, enabling clinicians to identify patients unlikely to benefit from postoperative AC and thus reduce the likelihood of overtreatment.

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Differences in Responses to Neoadjuvant Anti-HER2 Therapy between HER2 2+/ISH+ and HER2 3+ in HER2-Positive Breast Cancer: Lingjun Ma, Ran Zheng, Lingyun Xu, Ying Zhu, Hong Yin, Xiaoqing Zhang, Rong Deng, Jue Wang, Xiaoming Zha; Cancer Res Treat. 2026;58(2):501-512. Published online April 21, 2025; DOI: https://doi.org/10.4143/crt.2024.1200

Abstract PDF Supplementary Material PubReader ePub: Purpose
Dual anti–human epidermal growth factor receptor 2 (HER2) drugs have become the standard regimen for neoadjuvant systemic treatment (NST) to HER2-positive breast cancer patients. However, the efficacy varies greatly among patients with different HER2 protein expression levels.
Materials and Methods
A total of 575 HER2-positive breast cancer patients from multiple centers throughout China from 2013 to 2022 were retrospectively analyzed. We compared clinicopathological features in different HER2 immunohistochemistry classes (HER2 2+/in situ hybridization [ISH] + or HER2 3+), and their difference in response to NST and survival with single or dual anti-HER2 drugs. Drug sensitivity assays were used to evaluate different efficacy of anti-HER2 drugs in vitro.
Results
Compared to HER2 3+ subgroup, the HER2 2+/ISH+ group had a higher proportion of hormone receptor–positive status (48.7% vs. 76.1%, p < 0.001), more HER2 protein loss after NST, lower pathological complete response (pCR) rate (46.07% vs. 16.24%, p < 0.001), and tended to have worse disease-free survival (DFS). In HER2 2+/ISH+ patients, treated with pertuzumab and trastuzumab in combination had no significant improvement in pCR (19.12% vs. 12.24%, p=0.287) and DFS (p=0.908) than using alone. Drug sensitivity assay showed poor efficacy with dual anti-HER2 drugs in HER2 2+/ISH+ cell lines; however, fam-trastuzumab deruxtecan drugs had a satisfactory effect.
Conclusion
Owing to the differences in clinicopathological features and treatment efficacy, we considered the HER2 2+/ISH+ group to be a distinct subtype and defined it as the HER2-moderate–positive subgroup. In this subgroup, dual anti-HER2 drugs did not exert significant improvement in pCR and DFS. Therefore, treatment optimization is warranted, with antibody-drug conjugate drugs as potential options.

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The Impact of Obesity on Treatment Outcomes in Patients with Hormone Receptor–Positive HER2-Negative Metastatic Breast Cancer Receiving CDK 4/6 Inhibitors: Yoo Bin Jung, Hee Kyung Ahn, Hyun-Young Shin, Ji Hyung Hong, Chai Hong Rim; Cancer Res Treat. 2026;58(1):198-207. Published online April 15, 2025; DOI: https://doi.org/10.4143/crt.2025.110

Abstract PDF Supplementary Material PubReader ePub

Purpose
Guidelines from the aromatase inhibitor era for early breast cancer (EBC) treatment recommend maintaining a body mass index (BMI) below 25. In the current era of cyclin-dependent kinase (CDK) 4/6 inhibitors, now standard in metastatic breast cancer (MBC), limited data exist on treatment outcomes in obese patients. This study investigates how adiposity affects the treatment outcome of CDK 4/6 inhibitors in patients with hormone receptor–positive, human epidermal growth factor receptor 2–negative MBC.
Materials and Methods
We searched PubMed, MEDLINE, and Embase databases, assessing efficacy outcomes such as progression-free survival (PFS) based on obesity markers, including BMI and visceral adipose tissue (VAT) index.
Results
Twelve studies were reviewed, with seven studies and 1,812 patients included in a pooled meta-analysis. Among patients with BMI ≥ 25, modest improvement in PFS was observed, with a pooled hazard ratio (HR) of 0.944 (95% confidence interval [CI], 0.909 to 0.980; p=0.003). Besides, add-on analysis using VAT to define obesity revealed a notable PFS improvement, with a pooled HR of 0.452 (95% CI, 0.256 to 0.798; p=0.006).
Conclusion
While BMI-defined obesity showed slight PFS improvement with CDK 4/6 inhibitors and endocrine therapy, using VAT to define obesity revealed significant PFS gains. This highlights the need for further research on biomarker to clarify the role of adiposity in MBC, which may differ from its impact in EBC.

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Association Between Body Mass Index and Clinical Outcomes of CDK4/6 Inhibitors in HR+/HER2− Metastatic Breast Cancer: A Real-World Cohort Study
Seval Orman, Miray Aydoğan, Nisanur Sarıyar Busery, Sedat Yıldırım, Hacer Şahika Yıldız, Hamit Bal, Utku Dönem Gündoğdu, Seval Ay Ersoy, Deniz Işık, Hatice Odabaş, Nedim Turan
Journal of Clinical Medicine.2026; 15(4): 1671. CrossRef
Body Mass Index and Outcomes in HR+/HER2− Metastatic Breast Cancer Treated with Palbociclib: Insights from a National Real-World Study
Larisa Maria Badau, Paul Epure, Madalin-Marius Margan, Roxana Margan, Andrei Dorin Ciocoiu, Cristina Marinela Oprean, Brigitha Vlaicu
Cancers.2026; 18(9): 1379. CrossRef
Alternate actions of CDK4/6 inhibitors beyond cell cycle blockade: unexplored roles in therapy resistance
Domenica Scordamaglia, Marianna Talia, Azzurra Zicarelli, Adelina Assunta Mondino, Salvatore De Rosis, Marika Di Dio, Francesca Silvestri, Chiara Meliti, Francesca Cirillo, Ernestina Marianna De Francesco, Roberta Malaguarnera, Carlo Capalbo, Marcello Mag
Cancer and Metastasis Reviews.2025;[Epub] CrossRef

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143 Download
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3 Crossref

Spatial Transcriptomic Landscape of Brain Metastases from Triple-Negative Breast Cancer: Comparison of Primary Tumor and Brain Metastases Using Spatial Analysis: Jihwan Yoo, Inho Park, Hyun Jung Kim, Hun Ho Park, Sora Lee, Jee Hung Kim, Yoon Jin Cha; Cancer Res Treat. 2026;58(1):182-197. Published online April 15, 2025; DOI: https://doi.org/10.4143/crt.2025.033

Abstract PDF Supplementary Material PubReader ePub

Purpose
Triple-negative breast cancer (TNBC) is a particularly aggressive subtype of breast cancer, with approximately 30% of patients eventually developing brain metastases (BM), which result in poor outcomes. An understanding of the tumor microenvironment (TME) at both primary and metastatic sites offers insights into the mechanisms underlying BM and potential therapeutic targets.
Materials and Methods
Spatial RNA sequencing (spRNA-seq) was performed on primary TNBC and paired BM tissues from three patients, one of whom had previously received immune checkpoint inhibitors before BM diagnosis. Specimen regions were categorized into tumor, proximal, and distal TME based on their spatial locations. Gene expression differences across these zones were analyzed, and immune cell infiltration was estimated using TIMER. A gene module analysis was conducted to identify key gene clusters associated with BM.
Results
Distinct gene expression profiles were noted in the proximal and distal TMEs. In BM, the proximal TME exhibited neuronal gene expression, suggesting neuron-tumor interactions compared to tumor, and upregulation of epithelial genes compared to the distal TME. Immune cell analysis revealed dynamic changes in CD8+ T cells and macrophages across the tumor and TME zones. Gene module analysis identified five key modules, including one related to glycolysis, which correlated with patient survival. Drug repurposing analysis identified potential therapeutic targets, including VEGFA, RAC1, EGLN3, and CAMK1D.
Conclusion
This study provides novel insights into the transcriptional landscapes in TNBC BM using spRNA-seq, emphasizing the role of neuron-tumor interactions and immune dynamics. These findings suggest new therapeutic strategies and underscore the importance of further research.

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Rewiring Glycolysis in Cancer: From Tumor Initiation to Therapeutic Vulnerabilities
Shicai Sun, Lulu Jia, Ying Yu, Seung-Jun Jeong, Yan Zhang, Dongryeol Ryu, Guang Ta
Cells.2026; 15(9): 771. CrossRef

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273 Download
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Comparison of Long-term Oncological Outcome of Sentinel Lymph Node Mapping Methods (Dye-Only versus Dye and Radioisotope) in Breast Cancer Patients Following Neoadjuvant Chemotherapy: Jinyoung Byeon, Changjin Lim, Eunhye Kang, Ji-Jung Jung, Hong-Kyu Kim, Han-Byoel Lee, Hyeong-Gon Moon, Wonshik Han; Cancer Res Treat. 2026;58(1):175-181. Published online April 15, 2025; DOI: https://doi.org/10.4143/crt.2024.1253

Abstract PDF Supplementary Material PubReader ePub: Purpose
Sentinel lymph node biopsy (SLNB) using dye and isotope (DUAL) is recommended over the dye-only (DYE) method after neoadjuvant chemotherapy (NCT) due to potentially lower false-negative rates. However, the long-term outcome of either method is unclear. We aimed to compare the long-term oncological outcomes of DYE versus DUAL SLNB methods in patients who received NCT.
Materials and Methods
In this retrospective cohort study, 893 patients who underwent SLNB following NCT and had pathologically negative lymph nodes were included. After propensity score matching for cT, cN, and pT categories, 280 patients were in the DYE group and 560 in the DUAL group. Indigo carmine was used for dye and Tc-99m antimony trisulfate for isotope mapping.
Results
Median follow-up was 75.6 months in the DYE group and 83.0 months in the DUAL group. Mean (±standard deviation) number of harvested sentinel nodes was 6.7 (±3.9) and 6.7 (±3.3) in the DYE and DUAL groups (p=0.875). Five-year distant metastasisfree survival was 95.2% in DYE group and 93.3% in DUAL group (hazard ratio [HR], 1.45; 95% confidence interval [CI], 0.82 to 2.57; p=0.192). Disease-free survival (HR, 0.97; 95% CI, 0.69 to 1.50; p=0.914) and overall survival (HR, 0.98; 95% CI, 0.56 to 1.69; p=0.954) were not significantly different. Axillary recurrence rate was 1.8% and 2.5% in DYE and DUAL groups (p=0.647).
Conclusion
Long-term oncological outcomes did not significantly differ between DYE and DUAL SLNB methods. The dye-only method can be safely recommended for breast cancer patients who received NCT.

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