Clinical Cancer Research最新文献

{"title":"Repurposing Tumor Cells: A Paradigm Shift in Cell-Based Therapies for Cancer","authors":"Kok-Siong Chen, Laura Y. Lin, Yi-Ching Chen, Khalid Shah","doi":"10.1158/1078-0432.ccr-25-3438","DOIUrl":"https://doi.org/10.1158/1078-0432.ccr-25-3438","url":null,"abstract":"Conventional cancer therapies emphasize eradication, often at the expense of harming healthy tissue and immune compromise. This article explores a paradigm-shifting concept: repurposing tumor cells not merely as targets, but as active therapeutic agents. By harnessing their self-homing ability, antigen diversity, and adaptive survival mechanisms, these engineered tumor cells can be repurposed to deliver therapeutic payloads, remodel the tumor microenvironment, and even function as antigen-presenting cells. We begin by critically analyzing the mechanistic failures of early whole-cell vaccine approaches, highlighting how their limited efficacy stemmed from underestimating both the tumor’s potent adaptive resistance and the deeply immunosuppressive nature of its microenvironment. We then discuss next-generation strategies designed to overcome these hurdles, with approaches ranging from “killer vaccines” and APC-like reprogramming to Trojan horse delivery of oncolytic viruses. The translational challenges, ranging from multi-layered safety engineering, GMP manufacturing, regulatory navigation, patient selection, and ethical considerations, are examined in depth, with key insights drawn from the clinical evolution of CAR-T cell therapy. We conclude by outlining a clinical roadmap and rational combinatorial strategies, proposing that if these barriers are overcome, tumor cell-based therapies could emerge as complements to immune checkpoint inhibitors and adoptive cell therapies, thus transforming the tumor from an adversary into a catalyst of its own defeat.","PeriodicalId":10279,"journal":{"name":"Clinical Cancer Research","volume":"96 1","pages":""},"PeriodicalIF":11.5,"publicationDate":"2026-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146231076","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Abstract PS1-13-01: Effects of a physical exercise protocol via telehealth on the quality of life and stress of women undergoing chemotherapy: a randomized clinical trial","authors":"D. C. Silva, G. T. Tosello, D. G. D. Christofaro, W. R. Tebar","doi":"10.1158/1557-3265.sabcs25-ps1-13-01","DOIUrl":"https://doi.org/10.1158/1557-3265.sabcs25-ps1-13-01","url":null,"abstract":"Introduction: Although effective, chemotherapy is associated with physical and psychological adverse effects, including stress, which can impair quality of life (QoL). Physical exercise has been shown to effectively reduce stress and improve QoL in cancer patients. Telehealth has emerged as an alternative to expand access to exercise programs, overcoming logistical and financial barriers. Therefore, implementing telehealth-based exercise protocols for women undergoing chemotherapy is relevant to optimize comprehensive care in this population. Objetives: To evaluate the effect of a telehealth-based exercise protocol on quality of life and stress in women undergoing chemotherapy. Methods: This randomized clinical trial was approved by the Research Ethics Committee (47329721.6.0000.5402) and registered with the ReBEC (RBR-9mqyz6j). Forty-four women (48.36 ± 12.39 years) diagnosed with solid tumors and undergoing chemotherapy were randomized into an intervention group (IG, n=22) and a minimal intervention group (MIG, n=22). The IG performed a supervised telehealth exercise program, including flexibility, muscular endurance, cardiorespiratory fitness, and balance, three times per week for 20 minutes per session via video call. The MIG received guidance and follow-up to address questions regarding physical activity. QoL was assessed using the EORTC QLQ-C30 questionnaire (Global Health Status, Functional, and Symptom scales), where higher scores indicate better functioning and higher symptom burden. Physical and emotional stress was evaluated using Lipp's Stress Symptoms Inventory for Adults (alert ≥7 symptoms, resistance ≥4 symptoms, exhaustion ≥8 symptoms). For statistical analysis, ANOVA adjusted for age, sex, and socioeconomic status was applied to the EORTC QLQ-C30. Descriptive frequency analysis was used for the Lipp questionnaire, and the Smallest Worthwhile Change (SWC) index was applied to both questionnaires to identify clinically meaningful changes, complementing statistical tests. Results: The telehealth-based exercise protocol did not show statistically significant differences in QoL between groups. However, SWC analysis revealed slight improvements or maintenance in global health domains in the IG (improved: 8, maintained: 6, worsened: 8), as well as in the functional scale. Maintaining QoL values is considered a positive outcome, suggesting that interventions may help mitigate chemotherapy’s adverse effects. Evidence indicates that during chemotherapy, patients’ QoL tends to deteriorate regardless of treatment. Regarding stress, both groups showed increased symptom presence. SWC analysis revealed small clinical changes in the exhaustion phase and more pronounced improvements in the resistance phase in the IG (improved: 9, maintained: 4, worsened: 9) compared to the MIG (improved: 7, maintained: 0, worsened: 15). Conclusions: These findings suggest that the exercise protocol may have a more pronounced effect in the early stages of stress. ","PeriodicalId":10279,"journal":{"name":"Clinical Cancer Research","volume":"21 1","pages":""},"PeriodicalIF":11.5,"publicationDate":"2026-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146231092","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Abstract PS1-04-08: Five-year longitudinal sociodemographic and lifestyle trajectories among Mexican young women with breast cancer in the Joven & Fuerte cohort","authors":"F. P. Pons-Faudoa, F. Mesa-Chavez, A. Platas, B. F. Vaca-Cartagena, A. S. Ferrigno, A. Fonseca, M. Miaja, M. Cruz-Ramos, J. E. Bargallo-Rocha, P. Cabrera-Galeana, A. Mohar, C. Villarreal-Garza","doi":"10.1158/1557-3265.sabcs25-ps1-04-08","DOIUrl":"https://doi.org/10.1158/1557-3265.sabcs25-ps1-04-08","url":null,"abstract":"Background: Breast cancer (BC) diagnosis and treatment can significantly disrupt employment, reproductive, and health behaviors, particularly in young women, with lasting implications for quality of life. However, longitudinal data in Latin American populations remain scarce. This study aimed to characterize five-year sociodemographic and lifestyle trajectories among Mexican young women with BC (YWBC). Methods: Females aged ≤40 years diagnosed with stage I–III BC between 2015 and 2020 were enrolled in the Joven & Fuerte prospective multicenter cohort. Sociodemographic and lifestyle variables including occupational status, income, relationship status, fertility preferences and outcomes, and behaviors such as exercise, alcohol use, smoking, and spirituality were assessed using generalized estimating equations and multinomial logistic regression. Risk ratios (RR), relative risk ratios (RRR), and 95% confidence intervals (CI) were calculated relative to baseline. Data were collected at diagnosis, 6 months, 1 year, 2–3 years, and 4–5 years post-diagnosis. Due to the longitudinal design, missing data varied by variable and timepoint. Each analysis was calculated based on the number of respondents with available. Results: Among 526 participants (median age: 36 years; IQR: 32–38), 52.9% had education up to high school. At diagnosis, ∼40% were employed full- or part-time. Employment dropped at 6 months (RR = 0.46; 95% CI: 0.41–0.51) and 1 year (RR = 0.54; 95% CI: 0.49–0.60), both p < 0.001. Occupational changes, reported by 70% at diagnosis, increased at 2–3 years (RR = 1.15; 95% CI: 1.05-1.26; p = 0.003) and 4–5 years (RR = 1.23; 95% CI: 1.12-1.34; p < 0.001). Income reductions affected 67% at diagnosis and persisted, though likelihood declined at 4–5 years (RR = 0.74; 95% CI: 0.62–0.89; p = 0.001), suggesting partial financial recovery. Relationship status was stable: 78% had a partner at diagnosis; 75% stayed with the same partner at 6 months, and 68% at 4–5 years. Compared to this group, being with a different partner at 1 year (RRR = 0.24; 95% CI: 0.10–0.56; p < 0.001) or starting a new relationship at 2–3 years after being single (RRR = 0.31; 95% CI: 0.14–0.72; p = 0.006) was less likely. Fertility preferences declined: 39% desired biological children at diagnosis vs. 20% at 4–5 years (RR = 0.40; 95% CI: 0.17-0.95; p = 0.038). Fewer than 10 live births occurred, and most patients (95-99%) reported no attempts to conceive, with no significant change over time. Lifestyle behaviors improved during the study period. Physical inactivity dropped from 57% at diagnosis to 44% at 4–5 years. At follow-up participants were more likely to engage in <150 min/week (RRR = 1.80; 95% CI: 1.14-2.84; p = 0.01) or ≥150 min/week (RRR = 1.64; 95% CI: 1.07-2.51; p = 0.02). Alcohol intake declined: 2% consumed >20 drinks/week at diagnosis; nearly none by 4–5 years (p < 0.001). Less than 20 drinks/week intake also dropped at 6 m","PeriodicalId":10279,"journal":{"name":"Clinical Cancer Research","volume":"27 1","pages":""},"PeriodicalIF":11.5,"publicationDate":"2026-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146230642","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Abstract PS3-06-04: Spatial representation of deep-learning markers show additional prognostic value in breast cancer patients","authors":"C. Boissin, J. Hartman, M. Rantalainen","doi":"10.1158/1557-3265.sabcs25-ps3-06-04","DOIUrl":"https://doi.org/10.1158/1557-3265.sabcs25-ps3-06-04","url":null,"abstract":"Introduction: Intra-tumour heterogeneity has been hypothesised to increase risk of recurrence in breast cancer patients but has not been studied systematically. Deep-learning enables systematic extraction of prognostic information from H&E histopathology whole slide images (WSI), however, local tile level features are typically aggregated without spatial context. Research objective: To investigate the spatial distribution of an AI-based prognostic marker (DeepGrade) within tumour areas to identify patterns of spatial heterogeneity . Materials and Methods: 3325 WSIs from resected breast tumours of patients diagnosed in two hospitals in Sweden were used to predict DeepGrade status on a tile-level. Tumour regions were segmented and divided spatially into a tumour front and a tumour centre. For each tumour region, the total number of tiles, and the proportion of high-risk tiles were calculated. Clusters of high-risk tiles (regions of 25 neighboring tiles) were defined in the tumour front as a representation for tumour aggressiveness. Analyses were performed by tumour subtypes (Luminal A, Luminal B, Her2-enriched and Basal-like). Cox Proportional Hazards analyses was used to evaluate prognostic performance with progression free survial as primary endpoint. Results: The proportion of DeepGrade-high tiles in the centre area were higher in Her2+ and basal-like patients than luminal patients, (49.6% vs 12.8% had > 80% of centre tiles DeepGrade-high). In the subgroup of luminal patients (2268 patients), those who had a cluster of DeepGrade-high tiles in the tumour front area had higher recurrence propability with a multivariate hazard ratio of 1.97 (CI: 1.19-3.25; p-value=0.008); and within the subgroup of luminal patients with DeepGrade-low status (1356 patients), having a cluster in the tumour front had a univariate hazard ratio of 3.20, and a multivariate hazard ratio of 1.98 (CI: 1.13-3.49, p-value=0.017) when controlling for age, tumour size, lymph node status, and grade. Conclusions: The presence of at least one cluster of high-risk tiles within the tumour front was found to be an independent prognostic factor. More generally, the spatial distribution of high-risk tumour areas in a histopathology slides can have prognostic implications and should be characterised with greater detail in the future. Citation Format: C. Boissin, J. Hartman, M. Rantalainen. Spatial representation of deep-learning markers show additional prognostic value in breast cancer patients [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl): nr PS3-06-04.","PeriodicalId":10279,"journal":{"name":"Clinical Cancer Research","volume":"8 1","pages":""},"PeriodicalIF":11.5,"publicationDate":"2026-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146230795","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Abstract PS1-02-01: Knowledge, risk perception, and decision making in patients with a history of ductal carcinoma in situ (DCIS) or atypical breast lesions: a secondary analysis from the PORTAL Study","authors":"C. Valenza, S. M. Rosenberg, K. Crowell, K. L. Schreiber, I. Bedrosian, K. S. Hughes, T. Lynch, D. Basila, D. Collyar, E. S. Frank, S. Darai, C. Lanahan, J. R. Marks, J. K. Plichta, A. M. Thompson, T. Hyslop, S. Hwang, A. H. Partridge","doi":"10.1158/1557-3265.sabcs25-ps1-02-01","DOIUrl":"https://doi.org/10.1158/1557-3265.sabcs25-ps1-02-01","url":null,"abstract":"Background: The COMET trial demonstrated that active monitoring (AM) is not inferior to guideline concordant care (GCC) in patients with low-risk ductal carcinoma in situ (DCIS), with comparable rates of ipsilateral invasive breast cancer (iBC) and quality of life outcomes. Similarly, patients with atypical breast lesions have an increased risk of iBC and are managed with an AM strategy which could serve as a proxy for future omission of surgery in low-risk DCIS. Acknowledging that acceptance of treatment deintensification is likely linked to patient preferences, understanding, and risk perception, this analysis assessed these patient-reported outcomes (PROs) among patients with atypical breast lesions and DCIS. Methods: In this secondary analysis of the Patient-reported Outcomes after Routine Treatment of Atypical Lesions (PORTAL) Study - a multicenter cross-sectional survey study - we compared PROs from women with DCIS who received GCC, to women with high-risk breast lesions (e.g., atypical ductal hyperplasia [ADH], lobular intraepithelial neoplasia [LIN]) who underwent AM. We report on participants’ fear of invasive breast cancer (using Quality of Life in Adult Cancer Survivors [QLACS]), and disease understanding and decision quality (using Breast Cancer Surgery Decision Quality Instrument-Sections 1 and 3 [BCS-DQI-S1/3], SURE scale, Decision Regret Scale [DRS]; and Control Preferences Scale [CPS]). Descriptive statistics were provided, with means and standard deviations (SD), or proportions and 95% confidence intervals (CI). Results: 903 patients were included: 538 underwent GCC for DCIS; 365 underwent AM for ADH/LIN (Table). The mean QLACS score was 1.9/4 in both groups, indicating low to moderate fear of developing iBC, with minimal impact on quality of life. The mean knowledge of the natural history of breast lesions was 77% of patients in the DCIS group and 67% in the ADH/LIN group. In the DCIS group, 84% of patients received treatment aligned with their personal goals (concordance score, BCS-DQI-S1). Mean Decision Process Scores (BCS-DQI-S3) were 77% and 63%, respectively, indicating a high level of shared decision-making. According to the CPS, 61% of patients reported a collaborative role in decision-making. On average, there was low or no regret about treatment decision (DRSs were 12/100 and 10/100). Among patients with DCIS, 81% reported no decisional conflict (SURE scale). Conclusions: These findings suggest that women with ADH/LIN and DCIS report high levels of knowledge, goal-concordant care, and involvement in shared decision-making, potentially suggesting that AM is acceptable and presents a future opportunity to de-intensify treatment for low-risk DCIS, pending results of clinical trials. Citation Format: C. Valenza, S. M. Rosenberg, K. Crowell, K. L. Schreiber, I. Bedrosian, K. S. Hughes, T. Lynch, D. Basila, D. Collyar, E. S. Frank, S. Darai, C. Lanahan, J. R. Marks, J. K. Plichta, A. M. Thompson, T. Hyslop, S. Hwang, A. H. Pa","PeriodicalId":10279,"journal":{"name":"Clinical Cancer Research","volume":"7 1","pages":""},"PeriodicalIF":11.5,"publicationDate":"2026-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146230835","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Abstract PS1-02-27: Assessment of metabolic health in women with breast cancer: a prospective cohort study","authors":"V. Prado, D. Buttros, P. Amaral, G. Tosello, S. Rizzi, E. Nahas","doi":"10.1158/1557-3265.sabcs25-ps1-02-27","DOIUrl":"https://doi.org/10.1158/1557-3265.sabcs25-ps1-02-27","url":null,"abstract":"Introduction: Women diagnosed with breast cancer exhibit an elevated risk of weight gain and metabolic dysfunctions, which are associated with a decline in overall and specific survival rates. Interdisciplinary assessment at the time of diagnosis can positively influence prognosis and survival. This study aimed to evaluate the impact of breast cancer diagnosis and treatment on the metabolic health and survival of women undergoing treatment for breast cancer. Methods: This was a single-center, prospective cohort study that included women with a recent diagnosis of breast cancer, aged ≥ 40 years, without metastatic disease or established cardiovascular disease, who were followed for the first two years after breast cancer diagnosis. The criteria used for the assessment of metabolic health/dysfunction were the presence of obesity (body mass index, BMI ≥ 30kg/m2), hypertension (blood pressure, BP ≥ 130/85mmHg), hypertriglyceridemia (triglycerides, TG ≥ 150mg/dL), low high-density lipoprotein cholesterol (HDL < 50mg/dL), hyperglycemia (glucose > 100mg/dL), and the presence of metabolic syndrome (MetS, NCEP-ATPIII criteria). Clinical and anthropometric data (BP, BMI, and waist circumference/WC) were collected through interviews and physical examinations. Information on oncological treatments and tumor characteristics was extracted from medical records. Biochemical analyses included total cholesterol, HDL, LDL, TG, and glucose levels. Patients underwent interdisciplinary assessment (nutritional and psychological) at the time of diagnosis and continued with follow-up appointments with a breast specialist according to the service routine for 2 years. Assessments were conducted at five time points: initial consultation, and at six, 12, 18, and 24 months. Statistical analyses included non-parametric tests, logistic regression, and Kaplan-Meier survival analysis. Results: A total of 165 women were eligible for the study, of whom 39 dropped out during follow-up. The analysis included 126 women with a mean age of 59.0 ± 12.0 years and a mean BMI of 29.7 ± 5.8 kg/m2; 91% of tumors were in stages I and II, 71% had negative axillary lymph nodes, and 79% were luminal subtypes. Over the 2-year follow-up period, among the indicators of metabolic dysfunction, a significant reduction was observed in the occurrence of women with dysglycemia (p = 0.04), elevated systolic blood pressure (p<0.001), and reduced HDL levels (p = 0.03). There was no significant difference in the occurrence of obesity (p = 0.70), increased WC (p = 0.09), hypertriglyceridemia (p = 0.08), diastolic BP ≥ 85 mmHg (p = 0.30), or the presence of MS, which was present in 45% of women at breast cancer diagnosis and in 42%, 37%, 36%, and 35% at six, 12, 18, and 24 months, respectively (p = 0.40). Univariate logistic regression analyses did not demonstrate an impact of hormonal therapy, chemotherapy, or radiotherapy on the presence of metabolic dysfunctions (p>0.05). During f","PeriodicalId":10279,"journal":{"name":"Clinical Cancer Research","volume":"50 1","pages":""},"PeriodicalIF":11.5,"publicationDate":"2026-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146230843","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Abstract PS3-07-06: Real-world Prognostic Evaluation of Adjuvant Endocrine Therapy, Ovarian Function Suppression, and Chemotherapy in Premenopausal HR-positive/HER2-negative Early Breast Cancer in Japan: The PEACE Study","authors":"T. Shimoi, K. Narui, K. Kataoka, S. Orihara, K. Kida, R. Nakamura, K. Adachi, Y. Horimoto, M. Oshi, A. Yamada, K. Matsumoto, J. Tsurutani, Y. Kajiura, H. Nogi, S. Akashi-Tanaka, Y. Hasegawa, K. Wakita, T. Kubota, M. Taguri, T. Ishikawa","doi":"10.1158/1557-3265.sabcs25-ps3-07-06","DOIUrl":"https://doi.org/10.1158/1557-3265.sabcs25-ps3-07-06","url":null,"abstract":"Background: Premenopausal women with hormone receptor-positive, HER2-negative early breast cancer (HR+HER2- EBC) exhibit higher incidence rates in Asia than in Western populations. Chemotherapy (CT) is routinely recommended for premenopausal node-positive patients, while it remains unclear whether its apparent benefit derives primarily from ovarian function suppression (OFS). We therefore evaluated long-term outcomes of adjuvant endocrine therapy (ET) alone, ET plus OFS, and ET plus chemotherapy (±OFS) in a nationwide Japanese cohort, stratified by nodal status. Methods: We retrospectively analyzed 7,396 premenopausal HR+HER2- T1-4N0-1 patients who underwent surgery at 25 Japanese centers between January 2008 and December 2017. Patients were divided into node-positive (N1; n=2,041) and node-negative (N0; n=5,355) cohorts. Three treatment groups were defined: ET alone, ET+OFS, and ET +chemotherapy (±OFS). Survival probabilities of eight-year disease-free survival (DFS) and overall survival (OS) were estimated by Kaplan-Meier methods; hazard ratios (HRs) for treatment groups were estimated using Cox models with inverse probability of treatment weighting (IPTW) adjusted for age, tumor size, grade, receptor status, lymphovascular invasion, systemic treatment pattern, surgery type, and radiotherapy. Results: Median follow-up was 8.4 years. In the overall population (n=7,396), 8-year DFS and OS were 95.2% and 98.0%, respectively. Among N0 cohort (n = 5,355), 68.4% ≦T1 and 31.6% ≧T2. Histological grade 3 comprised 12.7%. ER positive in 82.3%; PgR positive in 75.1%. N0 patients’ 8-year DFS was 97.1% (95% CI 96.6-97.6), and 8-year OS 98.8% (95% CI 98.4-99.2), with no significant DFS benefit for ET+OFS or CT versus ET alone. Among N1 cohort, 42.1% ≦T1 and 58.8% ≧T2. Histological grade 3 comprised 28.5%. N1 patients’ 8-year DFS was 90.4% (95% CI 88.7-92.1), and 8-year OS 96.0% (95% CI 94.9-97.1). Compared with ET alone, ET+OFS conferred a significant DFS reduction, whereas CT did not reach significance. OS differences were non-significant in both subgroups. In a Cox model for DFS in N1 patients, the following factors were independently associated with statistically favorable DFS; ET+OFS treatment pattern (vs ET alone), PgR positive (vs PgR null). ET+Chemotherapy was favorable DFS trend with ET alone. Conclusions: Japanese premenopausal HR+HER2- EBC patients demonstrate excellent long-term survival, comparable to Western clinical-trial populations. In node-positive disease, OFS plus ET provided numerically greater DFS benefit than chemotherapy, suggesting that OFS may allow omission of chemotherapy in selected N1 patients. Prospective validation, is warranted to optimize adjuvant treatment in this population. Citation Format: T. Shimoi, K. Narui, K. Kataoka, S. Orihara , K. Kida , R. Nakamura , K. Adachi, Y. Horimoto, M. Oshi, A. Yamada, K. Matsumoto, J. Tsurutani, Y. Kajiura, H. Nogi, S. Akashi-Tanaka, Y. Hasegawa, K. Wakita, T. Kubota, M. Taguri, T. Ishika","PeriodicalId":10279,"journal":{"name":"Clinical Cancer Research","volume":"6 1","pages":""},"PeriodicalIF":11.5,"publicationDate":"2026-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146230883","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Abstract PS3-11-30: Neoadjuvant pyrotinib, trastuzumab, dalpiciclib, and exemestane in triple-positive breast cancer: a multicenter phase II trial","authors":"P. Fu, L. Chen, M. Yao, C. Du, Y. Li, J. Zhou, S. Chen, S. Cai, Q. Feng","doi":"10.1158/1557-3265.sabcs25-ps3-11-30","DOIUrl":"https://doi.org/10.1158/1557-3265.sabcs25-ps3-11-30","url":null,"abstract":"Background: Triple-positive breast cancer (TPBC), defined by concurrent expression of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2), accounts for 10-15% of breast cancers. Standard neoadjuvant regimens combining trastuzumab-based HER2-targeted therapy with chemotherapy show limited efficacy in this subtype. Resistance is attributed to HER receptor heterodimerization, HER2-ER signaling cross-talk, and activation of PI3K/AKT/mTOR pathways. Integrating HER2-targeted therapy with endocrine therapy and cyclin-dependent kinase 4/6 (CDK4/6) inhibitors may help overcome this resistance. The NA-PHER2 study demonstrated the potential benefit of a chemotherapy-free regimen, trastuzumab, pertuzumab, palbociclib, and fulvestrant, in TPBC. Pyrotinib, an irreversible pan-HER tyrosine kinase inhibitor, shows synergistic activity with CDK4/6 blockade in preclinical models. In the phase II MUKDEN 01 trial, pyrotinib combined with dalpiciclib and letrozole showed promise in TPBC, though efficacy remains suboptimal. Building on this rationale, we evaluated a novel, chemotherapy-free neoadjuvant regimen of pyrotinib, trastuzumab, dalpiciclib, and exemestane in patients with stage II-III TPBC. Methods: Eligible patients had previously untreated stage II-III TPBC, defined as ER >10%, PR >1%, and HER2 positivity (immunohistochemistry 3+ or in situ hybridization positive). Patients received pyrotinib (320 mg orally once daily, every 4 weeks, for 5 cycles), trastuzumab (intravenously: loading dose 8 mg/kg, then 6 mg/kg every 3 weeks for 6 cycles; or subcutaneously: 600 mg every 3 weeks for 6 cycles), dalpiciclib (125 mg orally once daily on days 1-21 of a 4-week cycle, for 5 cycles), and exemestane (25 mg orally once daily, every 4 weeks, for 5 cycles), followed by surgery. The primary endpoint was total pathological complete response (tpCR), defined as ypT0/is ypN0. Results: Between September 2022 and February 2025, 33 patients were enrolled. The median age was 48 years (range, 29-75). Disease stage at baseline included 17 patients (51.5%) with stage IIA, 11 (33.3%) with stage IIB, 4 (12.1%) with stage IIIA, and 1 (3.0%) with stage IIIC. Ki-67 expression at baseline was ≥30% in 25 patients (75.8%). As of June 10, 2025, 25 patients had undergone surgery with available pathological data. The tpCR rate was 24% (6 of 25; 95% confidence interval [CI], 10-46%). Residual cancer burden 0-1 was observed in 19 patients (76%; 95% CI, 54-90%), and 21 (84%; 95% CI, 63-95%) achieved a Miller-Payne grade 4-5 response. Among 31 patients with evaluable radiographic data, 12 achieved complete response and 19 had partial response, yielding an objective response rate of 100% (95% CI, 86-100%). Adverse events occurred most frequently during the first two treatment cycles. No grade ≥4 events were reported. The most common grade 3 adverse events were diarrhea (41.9%) and neutropenia (22.6%). Conclusions: This chemotherapy-","PeriodicalId":10279,"journal":{"name":"Clinical Cancer Research","volume":"2 1","pages":""},"PeriodicalIF":11.5,"publicationDate":"2026-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146231088","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Abstract PS4-04-06: Tumor-on-chip as a personalized platform for rapid drug testing in breast cancer","authors":"C. Helal, N. Schintu, J. Jin, L. Pinon, E. Montaudon, L. Sourd, H. Derrien, M. Nurmik, M. Simon, M. Parrini, L. Cabel, S. Descroix","doi":"10.1158/1557-3265.sabcs25-ps4-04-06","DOIUrl":"https://doi.org/10.1158/1557-3265.sabcs25-ps4-04-06","url":null,"abstract":"Background: Metastatic breast cancer (mBC) is the leading cause of cancer mortality in women, yet treatment selection in later lines remains empirical. Patient-derived xenografts (PDX) and organoids (PDO) have been shown to predict patient’s drug response, however their clinical utility for real-time clinical decision-making is limited by lengthy turnaround times and a low tumor take for luminal breast cancers, and rapid functional assays are urgently needed. We developed a microfluidic tumor-on-chip (ToC) for rapid exvivo chemosensitivity profiling to demonstrate the potential of ToC using cancer cells from BC PDX and a fresh patient's tumor sample. Methods: After tumor dissociation, tumor cells were isolated and embedded in 3D in collagen type I inside microfluidic device chips (AIMBiotech). Viability of tumor cells was assessed using a live/dead assay after several days of drug exposure (carboplatin, paclitaxel, 5-fluorouracil, and trastuzumab-deruxtecan if applicable) and compared to tumor growth measured invivo in the corresponding PDX model using a caliper. A panel of 6 PDX models was selected to reflect distinct BC subtypes and chemosensitivity profiles: 4 TNBC, 1 HER2 3+ and 1 ER+. To mimic clinical biopsies, we engineered a miniaturized chip by casting PDMS in 3D-printed silanized molds optimized for low cell input, and evaluated its performance using simulated core needle biopsies (18G) on PDX tumors and a patient sample. Results: We first investigated the response of ToC derived from fresh PDX samples. Differential drug responses were observed after 4 days of on-chip culture, suggesting that this duration is required to discriminate between sensitive and resistant models. The #152 PDX model (TNBC) showed a strong invivo response to carboplatin and paclitaxel, mirrored by a significant drop in cell viability on the ToC at D4. In contrast, neither mouse nor ToC responded to 5-FU. We performed live imaging to validate our endpoint measurement method, and comparable patterns of drug sensitivity were obtained. Overall, when a drug was identified as effective in the PDX model, we observed ToC sensitivity at D4 in 78 % of cases (in 7 cases out of 9, sensitivity was correctly detected on ToC in 6 PDX models using 4 drugs). Conversely, when the drug was resistant in PDX, we confirmed resistance in 100% of cases (11/11 using 3 drugs). Altogether, these findings highlight the correlation between the two models and demonstrate the ability of ToC platform to deliver rapid functional readouts within a clinically actionable timeframe of 4 days. Next, we successfully generated a functional ToC model using a fresh human primary tumor of TNBC; exposure to paclitaxel suggested tumor sensitivity. We finally developed an innovative microfluidic device compatible with patient biopsy samples. From three 18G core needle biopsies per tumor, we consistently isolated 100,000 to 200,000 viable tumor cells, allowing the generation of up to 12 individualized ToC un","PeriodicalId":10279,"journal":{"name":"Clinical Cancer Research","volume":"332 1","pages":""},"PeriodicalIF":11.5,"publicationDate":"2026-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146231089","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Abstract PS3-02-27: A Screening Paradox in TNBC: Exploring communities with High Late-stage Diagnosis Despite High Screening Uptake","authors":"C. Pisano, R. Abou Zeidane, F. Hussain, W. Dong, T. Lal, L. Vu, N. Mehta, C. Speers, S. M. Koroukian, J. Rose","doi":"10.1158/1557-3265.sabcs25-ps3-02-27","DOIUrl":"https://doi.org/10.1158/1557-3265.sabcs25-ps3-02-27","url":null,"abstract":"Introduction: Screening mammography has significantly reduced breast cancer mortality by enabling earlier diagnosis. Triple negative breast cancer (TNBC) is an aggressive subtype disproportionately affecting Black women. Given its aggressive nature and tendency to occur in younger women, understanding the role of screening in early detection of TNBC is critical. Accordingly, we sought to determine if common traits characterized communities where, despite high screening uptake, the proportion of patients presenting with late-stage TNBC (defined as presenting with regional or distant disease) remained elevated. By understanding characteristics of communities that appear to benefit less from screening, we hope to identify opportunities for intervention around improving the earlier diagnosis of TNBC. Methods: We identified women diagnosed with TNBC from 2010 to 2021 using SEER 22-Registry data (excluding Alaska). We calculated the proportion “late stage” in each county of the SEER regions. To ensure adequate sample sizes, we used the Max-P regionalization method to combine adjacent similar sociodemographic counties (determined by Area Deprivation Index) with ≤10 late-stage cases, creating composite counties (CC) as our unit of analysis. For each CC, we estimated the proportion of women up to date on mammography using CDC PLACES. We estimated community-level characteristics using the 2014-2018 American Community Survey 5-year data and CDC PLACES data including smoking, binge drinking, education, obesity. We used Classification and Regression Tree (CART) analysis to identify combinations of community characteristics associated with having a high (above median) proportion of late-stage TNBC despite having high (above median) mammography uptake. Results: The CART analysis delineated four distinct community profiles with varying rates of the outcome of interest. Communities with high proportions of Black residents (>25.8%) showed the highest rate of women with high screening uptake yet high late-stage TNBC at 63.2%. In contrast, communities with lower rates of binge drinking and lower Black population percentages showed the lowest rates (7.1%) of the same outcome. Conclusions: The study reveals that high screening uptake alone does not uniformly reduce late-stage TNBC, particularly in communities with higher percentages of Black residents or those with high-risk health behaviors (e.g. binge drinking). Future studies should assess the role that both system factors and racial differences in tumor biology play in this finding. Citation Format: C. Pisano, R. Abou Zeidane, F. Hussain, W. Dong, T. Lal, L. Vu, N. Mehta, C. Speers, S. M. Koroukian, J. Rose. A Screening Paradox in TNBC: Exploring communities with High Late-stage Diagnosis Despite High Screening Uptake [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl): nr PS3-02-27.","PeriodicalId":10279,"journal":{"name":"Clinical Cancer Research","volume":"32 1","pages":""},"PeriodicalIF":11.5,"publicationDate":"2026-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146231082","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}