Clinical breast cancer最新文献_第6页

Study on Different Staining Platforms for HER2 Cytoplasmic Granular Staining Pattern in Pure Apocrine Carcinoma of the Breast 乳腺纯大汗腺癌HER2细胞质颗粒染色不同染色平台的研究。

IF 2.5 3区医学 Q2 ONCOLOGY

Clinical breast cancer

Pub Date : 2026-01-01 DOI: 10.1016/j.clbc.2025.07.016

Xue-Xue Xiao , Peng-Fei Xu , Ming-Wei Wang , Su Jin , Na Fang , Jun-Qiu Yue

Objective

Accurate interpretation of HER2 low/ultralow expression has attracted increasing attention. This study aimed to explore the characteristics and interpretation strategies for the HER2 cytoplasmic granular staining pattern observed in pure apocrine carcinoma (AC), while investigating its impact on the interpretation of HER2 low/ultra-low expression cases.

Methods

The clinicopathologic information of 74 patients with pure AC and their previous HER2 (PATHWAY 4B5, Ventana platform) IHC results were retrospectively collected. All enrolled cases underwent Dako HER2 (HercepTest [poly]) IHC staining, among which 43 cases were further subjected to FISH testing. Clinical targeted drug information was collected concurrently.

Results

Previous PATHWAY 4B5 staining revealed punctate and/or diffuse cytoplasmic granular staining in 35.14% (26/74) of pure AC. In contrast, only 9 cases (12.16%, 9/74) of HercepTest staining exhibited cytoplasmic granular staining, all of which belonged to the PATHWAY 4B5 cytoplasmic granular staining subset (34.62%, 9/26). HercepTest IHC interpretation demonstrated 89.19% (66/74) concordance with PATHWAY 4B5 interpretations. Furthermore, 88.46% (23/26) of PATHWAY 4B5 cytoplasmic granular staining cases exhibited concordant interpretations between both antibody platforms. 44.59% (33/74) were HER2-positive, and 55.41% (41/74) were triple-negative apocrine carcinoma (TNAC). About 18.19% (6/33) of HER2-positive cases and 48.78% (20/41) of TNAC cases showed cytoplasmic granular staining on PATHWAY 4B5, and 95.00% (19/20) of the latter cases were HER2 low expression.

Conclusions

Pure ACs on the PATHWAY 4B5 platform primarily present HER2 cytoplasmic granular staining in TNAC and HER2 low expression cases. The rate of HER2 cytoplasmic granular staining on HercepTest platform was significantly lower than that of PATHWAY 4B5, and is more suitable for the detection and interpretation of HER2 0 and low expression cases.

目的：准确解释HER2低/超低表达越来越受到人们的关注。本研究旨在探讨纯大汗腺癌（AC）中观察到的HER2细胞质颗粒染色模式的特征和解释策略，同时研究其对HER2低/超低表达病例解释的影响。方法：回顾性收集74例单纯AC患者的临床病理资料及既往HER2 （PATHWAY 4B5， Ventana平台）免疫组化结果。所有入组病例均行Dako HER2 （HercepTest [poly]）免疫组化染色，其中43例进一步行FISH检测。同时收集临床靶向药物信息。结果：既往的PATHWAY 4B5染色显示35.14%（26/74）纯AC呈点状和/或弥漫性胞浆颗粒染色，而HercepTest染色仅9例（12.16%,9/74）为胞浆颗粒染色，均属于PATHWAY 4B5胞浆颗粒染色亚群（34.62%,9/26）。HercepTest IHC解释与PATHWAY 4B5解释的一致性为89.19%（66/74）。此外，88.46%（23/26）的PATHWAY 4B5细胞质颗粒染色病例在两种抗体平台之间表现出一致的解释。44.59%（33/74）为her2阳性，55.41%（41/74）为三阴性大汗腺癌（TNAC）。约18.19%（6/33）的HER2阳性病例和48.78%（20/41）的TNAC病例细胞质4B5呈颗粒状染色，后者为95.00%（19/20）的HER2低表达。结论：在TNAC和HER2低表达病例中，PATHWAY 4B5平台上的纯ACs主要呈现HER2细胞质颗粒染色。HercepTest平台上HER2细胞质颗粒染色率明显低于PATHWAY 4B5，更适合于her20及低表达病例的检测和解释。

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引用次数: 0

Trajectory of Chemotherapy-Induced Peripheral Neuropathy and Its Predictive Factors in Breast Cancer Patients: A Prospective Longitudinal Study 乳腺癌患者化疗诱导周围神经病变的发展轨迹及其预测因素：一项前瞻性纵向研究。

IF 2.5 3区医学 Q2 ONCOLOGY

Clinical breast cancer

Pub Date : 2026-01-01 DOI: 10.1016/j.clbc.2025.08.002

Huiqian Xu , Hong Li , Yijing Fan , Shufang Zhang , Yang Wang , Yiying Wang , Lizhi Zhou , Jinghua Zhang

Objective

To explore the trajectory patterns and influencing factors of chemotherapy-induced peripheral neuropathy (CIPN) in breast cancer patients using latent class growth analysis (LCGA).

Methods

This study was conducted from September 2022 to September 2023 at a tertiary hospital in Tangshan, China. A total of 350 hospitalized breast cancer patients undergoing chemotherapy were recruited. Data were collected through questionnaires, including general demographic information, disease-related characteristics, lifestyle factors, and psychological status. CIPN was assessed at 5 time points: baseline (T0) and the 21st day after the completion of the 1st (T1), 2nd (T2), 3rd (T3), and 4th (T4) chemotherapy cycles. Latent class growth models (LCGMs) were used to identify distinct trajectory patterns. Univariate analysis and multinomial logistic regression models were applied to examine the influencing factors.

Results

Three distinct CIPN trajectory groups were identified: the low-risk stable group (42.3%, n = 148), the moderate-risk progressive group (41.4%, n = 145), and the high-risk rapidly progressing group (16.3%, n = 57). Compared with the low-risk stable group, the predictive factors for the moderate-risk progressive group included body mass index (BMI), hypertension, and depression. For the high-risk rapidly progressing group, predictive factors included BMI, physical activity, social support, hypertension, vitamin D levels, nutritional status, and depression.

Conclusion

This study elucidates the heterogeneous trajectory patterns of chemotherapy-induced peripheral neuropathy (CIPN) in breast cancer patients and identifies key influencing factors. Recognizing these characteristics in clinical practice may facilitate the early identification of high-risk patients and enable timely interventions to mitigate CIPN severity.

目的：应用潜在类生长分析（LCGA）探讨乳腺癌化疗诱导周围神经病变（CIPN）的发展轨迹及影响因素。方法：本研究于2022年9月至2023年9月在中国唐山市某三级医院进行。共招募了350名接受化疗的住院乳腺癌患者。通过问卷调查收集数据，包括一般人口统计信息、疾病相关特征、生活方式因素和心理状态。CIPN在5个时间点进行评估：基线（T0）和第1 （T1）、第2 （T2）、第3 （T3）和第4 （T4）化疗周期完成后的第21天。潜在类别增长模型（LCGMs）用于识别不同的轨迹模式。采用单因素分析和多项logistic回归模型对影响因素进行分析。结果：确定了三个不同的CIPN轨迹组：低危稳定组（42.3%,n = 148），中危进展组（41.4%,n = 145）和高危快速进展组（16.3%,n = 57）。与低危稳定组相比，中度危进展组的预测因素包括体重指数（BMI）、高血压和抑郁。对于高危快速进展组，预测因素包括BMI、身体活动、社会支持、高血压、维生素D水平、营养状况和抑郁。结论：本研究阐明了乳腺癌患者化疗诱导的周围神经病变（CIPN）的异质性轨迹模式，并确定了关键影响因素。在临床实践中认识到这些特征可能有助于早期识别高风险患者，并能够及时干预以减轻CIPN的严重程度。

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引用次数: 0

A Systematic Review With Individual Patient Data Meta-analysis on Characteristics and Outcomes of Patients With Metaplastic Breast Carcinoma 对乳腺癌化生患者的特征和预后进行meta分析的系统综述。

IF 2.5 3区医学 Q2 ONCOLOGY

Clinical breast cancer

Pub Date : 2026-01-01 DOI: 10.1016/j.clbc.2025.06.002

Charlotte Caroline Hettwer , Georg W. Wurschi , Klaus Pietschmann

Metaplastic breast carcinoma (MBC) is a rare disease for which there is limited evidence from large prospective trials. This systematic review analyzed the characteristics, treatments, and outcomes of MBC patients reported in the literature until October 2024. PubMed and Web of Science were searched systematically for case reports or case series on MBC using predefined search terms according to PRISMA guidelines for systematic reviews (last search: October 2024; registered with Prospero: ID CRD42022356323). Three hundred eighty-four English-language articles (1978-2024) reporting on 491 patients diagnosed with MBC were included.

The median age at diagnosis was 53 years (range, 15-98 years). The median overall survival (OS) was 75.0 months, and median progression-free survival (PFS) was 36.0 ± 13.6 months (standard error). The most frequent locations of recurrence were the lung and local areas.

Univariate analysis revealed that increasing tumor size, publication before the year 2000, lymphadenopathy, metastasis, distant recurrence, and histopathological subtype significantly influenced OS (P < .05). Distant recurrence, metastasis, and year of publication before 2000 were identified as independent predictors of survival through multivariate Cox regression (P < .05).

Tumor size, the proliferation index (Ki-67), and histopathological subtype significantly influenced PFS (P < .05). Adjuvant therapy improved OS and PFS in patients with localized disease (M0) (P < .05).

This is the first systematic analysis of MBC, showing heterogeneous treatment patterns for localized and metastatic disease. Intensive multimodal therapy may improve tumor control and warrants further investigation. The significance of these results is limited by their retrospective nature and the inhomogeneity of single-case reports.

转移性乳腺癌（MBC）是一种罕见的疾病，大型前瞻性试验的证据有限。本系统综述分析了截至2024年10月文献报道的MBC患者的特征、治疗方法和结局。根据PRISMA系统评价指南，系统检索PubMed和Web of Science上的MBC病例报告或病例系列(最后检索时间：2024年10月；在普洛斯彼罗注册：ID CRD42022356323)。纳入了384篇英文文章（1978-2024），报道了491例被诊断为MBC的患者。诊断时的中位年龄为53岁（范围15-98岁）。中位总生存（OS）为75.0个月，中位无进展生存（PFS）为36.0±13.6个月（标准误差）。最常见的复发部位是肺和局部。单因素分析显示，肿瘤大小、2000年前发表、淋巴结病变、转移、远处复发和组织病理学亚型显著影响OS （P < 0.05）。通过多因素Cox回归，发现远处复发、转移和发表年份在2000年之前是独立的生存预测因素（P < 0.05）。肿瘤大小、增殖指数（Ki-67）和组织病理学亚型对PFS有显著影响（P < 0.05）。辅助治疗可改善局限性疾病患者的OS和PFS (M0) （P < 0.05）。这是对MBC的首次系统分析，显示了局部和转移性疾病的不同治疗模式。强化多模式治疗可改善肿瘤控制，值得进一步研究。这些结果的意义受限于它们的回顾性和单例报告的不同质性。

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引用次数: 0

The Role of Adjuvant Radiation Therapy in Treating Older Breast Cancer Patients With Low Adherence to Endocrine Therapy 辅助放射治疗在内分泌治疗依从性低的老年乳腺癌患者中的作用。

IF 2.5 3区医学 Q2 ONCOLOGY

Clinical breast cancer

Pub Date : 2026-01-01 DOI: 10.1016/j.clbc.2025.07.028

M. Judy Lubas , Jill Hasler , Jordan Fredette , Ana Sandoval-Leon , Richard J. Bleicher , Austin D. Williams , Lindsey Taylor , Joshua E. Meyer , Rebecca M. Shulman

Background

Older patients with hormone receptor-positive, human epidermal growth factor receptor 2 (HER2)-negative early-stage breast cancer (HPEsBC) typically undergo breast-conserving surgery (BCS) followed by adjuvant radiation therapy (RT) and/or endocrine therapy (ET). Our study aimed to identify predictors of low ET adherence and evaluate the role of RT in modifying survival among patients with low ET adherence.

Methods

A retrospective analysis was performed using a US-based, electronic health record-derived, de-identified database. Patients aged ≥65 years with HPEsBC treated with BCS from 2011 to 2018 were included. Four adjuvant treatment groups were identified. Low ET adherence was defined as ET use for <80% of the 5-year post surgery follow-up period. Multinomial logistic regression was used to identify predictors of low adherence. Survival outcomes were assessed using hazard ratios (HRs) adjusted for covariates.

Results

A total of 1,488 patients were included in the study. Among patients receiving ET, 23% demonstrated low adherence. After adjustment for covariates, mortality was higher for RT alone (HR = 1.79, p = .011) and no adjuvant therapy (HR = 2.65, p < .001) compared with ET + RT. Predictors of low ET adherence included increasing age (odds ratio [OR] = 1.06, p < .010) and treatment at an academic practice (OR = 2.58, p < .001). A 10% decline in ET adherence was associated with increased mortality (HR = 1.17, p < .001). An interaction analysis revealed no differential effect of RT in the context of ET adherence.

Conclusion

Low ET adherence occurred in approximately one-quarter of patients and was associated with advancing age and treatment at academic centers. Reduced ET adherence was linked to significantly increased mortality. Further investigation into the role of RT in patients with low ET adherence is warranted.

背景：激素受体阳性，人表皮生长因子受体2 （HER2）阴性的早期乳腺癌（HPEsBC）的老年患者通常接受保乳手术（BCS），然后进行辅助放射治疗（RT）和/或内分泌治疗（ET）。我们的研究旨在确定低ET依从性的预测因素，并评估RT在改善低ET依从性患者生存中的作用。方法：使用基于美国的电子健康记录衍生的去识别数据库进行回顾性分析。纳入2011年至2018年接受BCS治疗的年龄≥65岁的HPEsBC患者。确定了四个辅助治疗组。低ET依从性被定义为ET使用的结果：共有1488名患者纳入研究。在接受ET治疗的患者中，23%表现出低依从性。调整协变量后，与ET + RT相比，单独RT组（HR = 1.79, p = 0.011）和无辅助治疗组（HR = 2.65, p < 0.001）的死亡率更高。低ET依从性的预测因素包括年龄增加（优势比[OR] = 1.06, p < 0.010）和学术实践治疗（OR = 2.58, p < 0.001）。ET依从性下降10%与死亡率增加相关（HR = 1.17, p < 0.001）。相互作用分析显示，在ET依从性的背景下，RT没有差异效应。结论：低ET依从性发生在大约四分之一的患者中，并且与年龄的增长和学术中心的治疗有关。降低ET依从性与死亡率显著增加有关。进一步研究RT在低ET依从性患者中的作用是必要的。

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引用次数: 0

Appropriate Treatment for Stage 1 and 2 Her2-Positive and Triple-Negative Breast Cancer by Immigration Status in Ontario, Canada 加拿大安大略省移民身份对1期和2期her2阳性和三阴性乳腺癌的适当治疗

IF 2.5 3区医学 Q2 ONCOLOGY

Clinical breast cancer

Pub Date : 2026-01-01 DOI: 10.1016/j.clbc.2025.07.013

Omolara Fatiregun , Rinku Sutradhar , Sho Podolsky , Andrea Eisen , Lawrence Paszat , Eileen Rakovitch

Purpose

This study explored appropriate treatment received for stage 1 and 2 Her2-positive and triple-negative (TN) breast cancer (BC) among immigrants and long-term residents.

Methods

We identified women aged 18- 75 years diagnosed with BC in Ontario from 2012 to 2019. We stratified them into immigrants and long-term residents using the Immigration, Refugee, and Citizenship Canada Permanent Resident database (CIC). We linked to population-wide treatment databases to extract information on breast surgery, chemotherapy, and radiotherapy. We categorized them into 4 mutually exclusive groups based on subtype (Her-2 positive or TNBC) and breast surgery (breast-conserving surgery (BCS) vs. mastectomy). Appropriate treatment included chemotherapy for all (plus Herceptin if Her-2 overexpressing), plus breast radiation therapy if breast-conserving surgery was performed. We could not assess the receipt of endocrine therapy for the hormone receptor-positive subset of Her-2 overexpressors, or indications for postmastectomy radiation therapy. Odds ratios for receiving appropriate treatment were calculated using logistic regression, adjusting for age, resource utilization and area-level residential ethnicity concentration.

Results

Crude and univariate analyses showed no differences in the receipt of appropriate treatment. Similarly, adjusted analyses in each of the 4 subgroups showed no difference between immigrants and long-term residents. Among Her2-positive treated by(BCS) group,(Odds Ratio[OR] = 0.82, 95% Confidence Interval[CI] 0.65-1.03, and treated by mastectomy, OR = 0.95 (95% CI, 0.67-1.35). Among TNBC treated by BCS, OR = 0.81 (95% CI, 0.58-1.13), and treated by mastectomy,OR 0.85 (95% CI, 0.49-1.46).

Conclusion

Immigration status was not associated with the receipt of appropriate treatment amongst early-stage Her2-positive or TNBC breast cancer in Ontario.

目的：本研究探讨移民和长期居民中1期和2期her2阳性和三阴性（TN）乳腺癌（BC）的适当治疗方法。方法：我们选取了2012年至2019年在安大略省诊断为BC的18- 75岁女性。我们使用加拿大移民、难民和公民身份永久居民数据库（CIC）将他们分为移民和长期居民。我们连接到人口范围的治疗数据库，提取有关乳房手术、化疗和放疗的信息。我们根据亚型（Her-2阳性或TNBC）和乳房手术（保乳手术（BCS） vs乳房切除术）将其分为4个相互排斥的组。适当的治疗包括所有患者的化疗（如果Her-2过表达，则加用赫赛汀），如果进行保乳手术，则加用乳房放射治疗。我们无法评估Her-2过表达者中激素受体阳性亚群接受内分泌治疗的情况，也无法评估乳房切除术后放射治疗的适应症。使用逻辑回归计算接受适当治疗的优势比，调整年龄、资源利用和地区水平居住种族浓度。结果：粗分析和单因素分析显示，在接受适当治疗方面没有差异。同样，在4个亚组中进行的调整分析显示，移民和长期居民之间没有差异。在her2阳性（BCS）组中，（优势比[OR] = 0.82, 95%可信区间[CI] 0.65-1.03），(OR] = 0.95 （95% CI, 0.67-1.35）。在接受BCS治疗的TNBC中，OR = 0.81 (95% CI, 0.58-1.13)，而接受乳房切除术治疗的TNBC，OR = 0.85 （95% CI, 0.49-1.46）。结论：安大略省早期her2阳性或TNBC乳腺癌患者的移民身份与接受适当治疗无关。

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引用次数: 0

The Effects of Compression Therapy at Different Pressure Levels on Chemotherapy-Induced Peripheral Neuropathy in Breast Cancer Patients: A Randomized Controlled Trial 不同压力水平的压迫治疗对乳腺癌化疗诱导的周围神经病变的影响：一项随机对照试验。

IF 2.5 3区医学 Q2 ONCOLOGY

Clinical breast cancer

Pub Date : 2026-01-01 DOI: 10.1016/j.clbc.2025.08.009

Hong Li , Yijing Fan , Huiqian Xu , Haihong Qu , Yang Wang , Dandan Yu , Lizhi Zhou

Purpose

This study aims to examine the effects of compression therapy at different pressure levels on chemotherapy-induced peripheral neuropathy (CIPN).

Methods

A total of 108 breast cancer patients who developed CIPN after their first albumin-bound paclitaxel chemotherapy were randomly divided into 3 groups(1:1:1): control group, experimental group 1 (Grade II pressure: 23-32 mmHg), and experimental group 2 (Grade III pressure: 34-46 mmHg). The control group was given standard care, while the experimental groups underwent compression therapy in addition to standard care. CIPN incidence, symptom severity, and its impact on activities of daily living (ADL) were assessed at baseline, after the completion of the third and fifth chemotherapy cycles.

Results

After completing 3 chemotherapy cycles, CIPN incidence did not differ significantly among the groups (P > .05). After 5 cycles, the incidence of CIPN (≥ Grade 1) was significantly lower in both experimental groups compared to the control group (P < .05), with Experimental Group 2 also showing lower CIPN incidence (≥ Grade 2) than the control and Experimental Group 1 (P < .05). Both Grade II and III compression therapies alleviated CIPN symptoms and improved ADL, but Experimental Group 2 demonstrated superior efficacy after 5 cycles (P < .05). Significant differences in symptom severity and ADL impact were observed across group, time, and interaction effects (P < .001).

Conclusion

Compression therapy reduces CIPN incidence, alleviates symptoms, and improves ADL. Over longer intervention periods, Grade III pressure yields superior outcomes.

目的：本研究旨在探讨不同压力水平的压迫治疗对化疗诱导的周围神经病变（CIPN）的影响。方法：将首次白蛋白结合紫杉醇化疗后发生CIPN的乳腺癌患者108例随机分为3组（1:1:1）：对照组、实验1组（II级压力：23-32 mmHg）、实验2组（III级压力：34-46 mmHg）。对照组给予标准治疗，实验组在标准治疗的基础上进行压迫治疗。在完成第三和第五个化疗周期后，基线时评估CIPN发生率、症状严重程度及其对日常生活活动（ADL）的影响。结果：完成3个化疗周期后，各组间CIPN发生率无显著差异（P < 0.05）。5个疗程后，两组患者CIPN（≥1级）发生率均显著低于对照组（P < 0.05），且实验组2 CIPN（≥2级）发生率均低于对照组和实验组1 （P < 0.05）。II级和III级压缩治疗均能减轻CIPN症状，改善ADL，但实验2组在5个周期后疗效更优（P < 0.05）。症状严重程度和ADL影响在组间、时间和相互作用方面存在显著差异（P < 0.001）。结论：压迫治疗可降低CIPN发生率，减轻症状，改善ADL。在较长的干预时间内，III级压力效果更好。

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引用次数: 0

Re: Bridging Gaps in Remote Cancer Care: Commentary on the Adjuvant Abemaciclib Monitoring Model 关于：弥合远程癌症治疗的差距：对辅助Abemaciclib监测模型的评论。

IF 2.5 3区医学 Q2 ONCOLOGY

Clinical breast cancer

Pub Date : 2026-01-01 DOI: 10.1016/j.clbc.2025.08.005

Nicole L. Brown , Ann Tivey , Caroline Wilson , Fiona Britton , Sacha J. Howell

引用次数: 0

The USP8/CEP55/CHMP6 Axis Orchestrates Triple-Negative Breast Cancer Progression by Regulating Ferroptosis and Macrophage M2 Polarization USP8/CEP55/CHMP6轴通过调节铁凋亡和巨噬细胞M2极化来协调三阴性乳腺癌的进展。

IF 2.5 3区医学 Q2 ONCOLOGY

Clinical breast cancer

Pub Date : 2026-01-01 DOI: 10.1016/j.clbc.2025.08.003

Lin Wang , Ye Wang , Changgen Liu , Yixin Zhao

Background

Triple-negative breast cancer (TNBC) carries a substantial risk of recurrence and metastasis, posing significant threats to patients’ health and quality of life. Centrosomal protein 55 (CEP55) has been demonstrated to exhibit elevated expression levels in TNBC. However, its molecular regulatory mechanism in TNBC remains unclear.

Methods

Bioinformatics databases, qRT-PCR, and Western blot were employed to analyze CEP55 expression in TNBC tissues and cells. EdU assays, flow cytometry, and Transwell assays were utilized to monitor cell proliferation, apoptosis, and invasion. Subsequently, macrophage polarization was detected by flow cytometry. Fe²⁺, malondialdehyde (MDA), glutathione (GSH), and reactive oxygen species (ROS) levels were determined using corresponding kits. Immunoprecipitation (IP) was used to detect the ubiquitination level of CEP55, and co-IP was applied to confirm the interaction between CEP55 and Charged Multivesicular Body Protein 6 (CHMP6). Finally, a xenograft tumor model was established, and immunohistochemistry (IHC) was conducted to evaluate the expression of specific proteins.

Results

CEP55 levels were increased in TNBC tissues and cells. Silencing CEP55 repressed TNBC cell proliferation, invasion, and macrophage M2 polarization, and facilitated cell apoptosis and ferroptosis. Additionally, ubiquitin-specific protease 8 (USP8) maintained CEP55 stability through deubiquitination, and CEP55 overexpression reversed the cellular effects caused by USP8 knockdown. Moreover, CEP55 bound to CHMP6 to promote its expression, thereby facilitating the malignant progression of TNBC cells. CEP55 overexpression abolished the inhibitory influence of USP8 silencing on tumor growth in vivo.

Conclusion

USP8 stabilized CEP55 expression through deubiquitination, and CEP55 further promoted CHMP6 expression to inhibit ferroptosis progression, thereby facilitating macrophage M2 polarization and malignant biological behaviors of TNBC cells.

背景：三阴性乳腺癌（TNBC）具有很大的复发和转移风险，对患者的健康和生活质量构成重大威胁。中心体蛋白55 （CEP55）已被证实在TNBC中表达水平升高。然而，其在TNBC中的分子调控机制尚不清楚。方法：采用生物信息学数据库、qRT-PCR和Western blot技术分析CEP55在TNBC组织和细胞中的表达。EdU法、流式细胞术、Transwell法监测细胞增殖、凋亡和侵袭。随后用流式细胞术检测巨噬细胞极化。采用相应试剂盒检测Fe2+、丙二醛（MDA）、谷胱甘肽（GSH）、活性氧（ROS）水平。采用免疫沉淀法（Immunoprecipitation， IP）检测CEP55的泛素化水平，采用协同沉淀法（co-IP）确定CEP55与带电多泡体蛋白6 （charge Multivesicular Body Protein 6, CHMP6）的相互作用。最后，建立异种移植瘤模型，免疫组化（IHC）评价特异性蛋白的表达。结果：TNBC组织和细胞中CEP55水平升高。沉默CEP55可抑制TNBC细胞增殖、侵袭和巨噬细胞M2极化，促进细胞凋亡和铁死亡。此外，泛素特异性蛋白酶8 （USP8）通过去泛素化维持CEP55的稳定性，并且CEP55过表达逆转了USP8敲低引起的细胞效应。此外，CEP55结合CHMP6促进其表达，从而促进TNBC细胞的恶性进展。在体内，CEP55过表达消除了USP8沉默对肿瘤生长的抑制作用。结论：USP8通过去泛素化作用稳定CEP55的表达，CEP55进一步促进CHMP6的表达，抑制铁凋亡的进展，从而促进TNBC细胞巨噬细胞M2极化和恶性生物学行为。

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引用次数: 0

Bridging Gaps in Remote Cancer Care: Commentary on the Adjuvant Abemaciclib Monitoring Model 弥合远程癌症治疗的差距：对辅助Abemaciclib监测模型的评论。

IF 2.5 3区医学 Q2 ONCOLOGY

Clinical breast cancer

Pub Date : 2026-01-01 DOI: 10.1016/j.clbc.2025.10.005

Javed Iqbal , Brijesh Sathian , Syed Muhammad Ali , Ayesha parvaiz malik

引用次数: 0

Multiomics Analysis for Predicting Pathological Complete Response in Triple-Negative Breast Cancer and Reflecting Tumor Heterogeneity 预测三阴性乳腺癌病理完全缓解和反映肿瘤异质性的多组学分析。

IF 2.5 3区医学 Q2 ONCOLOGY

Clinical breast cancer

Pub Date : 2026-01-01 DOI: 10.1016/j.clbc.2025.08.014

Yufei Wang , Lingfeng Ma , Shijin Yuan , Zhuo Wang , Xian Wang

Background

Heterogeneity in triple-negative breast cancer (TNBC) leads to different responses to neoadjuvant chemotherapy (NAC). NAC-resistant TNBC is often associated with higher risk of recurrence and poor prognosis. This study developed and validated a novel radiomics-based model to predict pathological complete response (pCR) to NAC and reflect tumor heterogeneity in TNBC.

Methods

169 TNBC patients who underwent NAC between 2013 and 2023 were screened as a training cohort. A validation cohort and 2 cohorts containing RNA-seq data were also included. Radiomics features were extracted from dynamic contrast enhanced MRI (DCE-MRI) for model construction. Based on the model, we calculated the radiomics score (Rad-score) of each patient. The predictive capacity of the model was evaluated by area under receiver operating characteristic (ROC) curves. RNA-seq data was used to evaluate drug sensitivity, enriched pathways, and tumor microenvironment (TME) characteristics.

Results

The radiomics model can predict pCR in both the training cohort (AUC = 0.902) and validation cohort (AUC = 0.775). The high Rad-score subgroup exhibited better response to chemotherapy and better prognosis. Immune activation-related pathways were also enriched in the high-score subgroup. The low-score subgroup showed enrichment of TGF-β-related pathways and was more sensitive to TGF-β inhibitor. The model can also identify immune phenotypes (AUC = 0.85). The high Rad-score subgroup had abundant immune cell infiltration, while the low Rad-score subgroup was lacking immune cells in TME.

Conclusion

The model can effectively predict the pCR of TNBC and reflect tumor heterogeneity. Chemotherapy combined with targeting the TGF-β pathway is a potential strategy to overcome drug resistance in TNBC.

背景：三阴性乳腺癌（TNBC）的异质性导致对新辅助化疗（NAC）的不同反应。耐nac的TNBC通常与较高的复发风险和不良预后相关。本研究开发并验证了一种新的基于放射组学的模型，用于预测NAC的病理完全反应（pCR），并反映TNBC中肿瘤的异质性。方法：2013年至2023年间接受NAC治疗的169例TNBC患者作为培训队列进行筛选。还包括一个验证队列和2个包含RNA-seq数据的队列。从动态对比增强MRI （DCE-MRI）中提取放射组学特征用于模型构建。基于该模型，我们计算每位患者的放射组学评分（Rad-score）。用受试者工作特征（ROC）曲线下面积评价模型的预测能力。RNA-seq数据用于评估药物敏感性、富集通路和肿瘤微环境（TME）特征。结果：放射组学模型可以预测训练队列（AUC = 0.902）和验证队列（AUC = 0.775）的pCR。rad评分高的亚组对化疗反应较好，预后较好。在高评分亚组中，免疫激活相关通路也丰富。低评分亚组TGF-β相关通路富集，对TGF-β抑制剂更敏感。该模型还能识别免疫表型（AUC = 0.85）。高评分组免疫细胞浸润丰富，低评分组免疫细胞缺乏。结论：该模型能有效预测TNBC的pCR，反映肿瘤的异质性。化疗联合靶向TGF-β途径是克服TNBC耐药的潜在策略。

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引用次数: 0