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PMAIP1 Enhances DNA Damage and Induces ROS-Mediated Mitochondrial Dysfunction to Suppress Tumorigenesis in Triple-Negative Breast Cancer PMAIP1增强DNA损伤并诱导ros介导的线粒体功能障碍抑制三阴性乳腺癌的肿瘤发生
IF 2 4区 医学 Q3 OBSTETRICS & GYNECOLOGY Pub Date : 2025-12-30 DOI: 10.1155/tbj/7056712
Fangjian Shang, Lei Xu, Hongzhi Liu, Xin Dong, Huangfei Wu, Liping Yin, Lijuan Yan, Yixin Qi, Liyan Zhao

Background

PMAIP1 (NOXA) is a pro-apoptotic factor that is closely related to cancer development, but its role in triple-negative breast cancer (TNBC) is unclear. This study aimed to explore the effect of PMAIP1 on TNBC cell viability, apoptosis, DNA damage, and mitochondrial function.

Methods

qRT-PCR and western blot were used to detect the expression level of PMAIP1 in TNBC tissues and cells, and its biological role was evaluated in combination with MTT, TUNEL, comet assay, and mitochondrial function indicators (ROS, ATP, mtDNA, and JC-1).

Results

PMAIP1 is significantly upregulated in TNBC and is negatively correlated with cell viability: Overexpression of PMAIP1 inhibits cell viability, while knockdown of PMAIP1 enhances viability. Upregulation of PMAIP1 promotes apoptosis by increasing the Bax/Bcl-2 ratio, induces DNA damage, elevates ROS levels, and reduces ATP, mtDNA, and JC-1 levels, leading to mitochondrial dysfunction; conversely, knockdown of PMAIP1 alleviates these changes.

Conclusion

PMAIP1 exerts a tumor suppressor effect by regulating apoptosis, DNA damage, and mitochondrial dysfunction, providing potential target support for the treatment of TNBC.

背景:PMAIP1 (NOXA)是一种促凋亡因子,与癌症发展密切相关,但其在三阴性乳腺癌(TNBC)中的作用尚不清楚。本研究旨在探讨PMAIP1对TNBC细胞活力、凋亡、DNA损伤和线粒体功能的影响。方法:采用qRT-PCR和western blot检测PMAIP1在TNBC组织和细胞中的表达水平,并结合MTT、TUNEL、comet试验及线粒体功能指标(ROS、ATP、mtDNA、JC-1)评价其生物学作用。结果:PMAIP1在TNBC中显著上调,且与细胞活力呈负相关:PMAIP1过表达抑制细胞活力,PMAIP1敲低增强细胞活力。PMAIP1上调通过增加Bax/Bcl-2比值促进细胞凋亡,诱导DNA损伤,升高ROS水平,降低ATP、mtDNA和JC-1水平,导致线粒体功能障碍;相反,PMAIP1基因的敲低可以缓解这些变化。结论:PMAIP1通过调控细胞凋亡、DNA损伤、线粒体功能障碍等发挥抑瘤作用,为TNBC的治疗提供潜在靶点支持。
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引用次数: 0
Fear of Cancer Recurrence Contributes Largely to Patient Anxiety and Depression and Quality of Life in a Prospective Cohort of Chinese Breast Cancer Patients for Postoperative Radiotherapy 对癌症复发的恐惧在很大程度上影响了中国乳腺癌术后放疗患者的焦虑、抑郁和生活质量。
IF 2 4区 医学 Q3 OBSTETRICS & GYNECOLOGY Pub Date : 2025-12-22 DOI: 10.1155/tbj/5788053
Zhensheng Li, Yunjiang Liu, Yue Li, Yuguang Shang, Jun Zhang, Xiaohui Ji, Zhiping Zhao, Xuejuan Duan, Wenhui Geng, Junpu Yin
<div> <section> <h3> Background</h3> <p>Fear of cancer recurrence (FCR) is common among Chinese breast cancer (BC) patients following surgery, chemotherapy, and radiotherapy (RT). Understanding the prevalence and impact of FCR, particularly during the RT period, on anxiety, depression, and quality of life may inform strategies to manage patient distress.</p> </section> <section> <h3> Methods</h3> <p>From July 2015 to December 2016, 486 women undergoing RT for BC at the Fourth Hospital of Hebei Medical University, China, were prospectively enrolled in the study. Anxiety, depression, and quality-of-life changes were assessed using the Hospital Anxiety and Depression Scale (HADS) and the European Organization for Research and Treatment of Cancer’s Quality-of-Life questionnaires (QLQ-C30, QLQ-BR23) before and after RT. FCR was assessed using a modified question from the QLQ-BR23, <i>“how much have you worried about tumor recurrence (over the last week),”</i> which demonstrated the satisfactory construct validity and reliability in a prior pilot study. ANOVA, multivariate linear regressions, and ordinal logistic regressions were performed to evaluate odds ratio (OR) and <i>p</i> values. Pain and sleep disturbance were included as covariates in secondary models.</p> </section> <section> <h3> Results</h3> <p>Of the 486 women enrolled, 23 (4.7%) patients declined participation. Of the 463 analyzed patients, the mean age was 47 years old. 386 patients (83.4%) elected for mastectomies. FCR levels prior to RT were reported as “<i>none</i>” (29.4%), “<i>a little bit</i>” (51.2%), “<i>some</i>” (12.1%), and “<i>very much</i>” (7.3%). Increased FCR severity was associated with elevated median anxiety score (1.5, 5.0, 7.0, 8.5) and increased rates of clinically significant anxiety (anxiety score ≥ 11; 0%, 3.4%, 12.5%, 26.5%). Similarly, median depression scores (2.0, 4.0, 6.0, 6.5) rose with FCR severity, accompanied by higher prevalence of atypical depression (depression score ≥ 11; 2.2%, 3.4%, 5.4%, 17.7%) (all <i>p</i> < 0.001). Compared to the reference “<i>none,”</i> each unit increase of FCR severity was independently associated with one category (“<i>normal</i>,” “<i>borderline</i>,” and “<i>abnormal</i>”) of increased anxiety with OR (<i>p</i>) of 2.593 (<i>p</i> = 0.011), 5.889 (<i>< 0.001</i>), and 14.621 (<i>< 0.001</i>) and increased depression with OR (<i>p</i>) of 2.406 (<i>0.008</i>), 3.045 (<i>0.009</i>), and 7.210 (<i>< 0.001</i>), respectively. FCR severity was negatively associated with most quality-of-life domains (<i>p</i> < 0.05). Similar associations persisted post RT.</p> </section> <section>
背景:对癌症复发的恐惧(FCR)在中国乳腺癌(BC)患者手术、化疗和放疗(RT)后普遍存在。了解FCR的患病率及其对焦虑、抑郁和生活质量的影响,特别是在放疗期间,可以为管理患者痛苦的策略提供信息。方法:2015年7月至2016年12月,在中国河北医科大学第四医院接受BC RT治疗的486名女性前瞻性纳入研究。使用医院焦虑和抑郁量表(HADS)和欧洲癌症研究和治疗组织的生活质量问卷(QLQ-C30, QLQ-BR23)评估rt前后的焦虑、抑郁和生活质量变化。FCR使用QLQ-BR23的修改问题“你有多担心肿瘤复发(在过去一周)”进行评估,这在先前的初步研究中证明了令人满意的结构效度和信度。采用方差分析、多元线性回归和有序逻辑回归来评价比值比(OR)和p值。疼痛和睡眠障碍被纳入二级模型的协变量。结果:在纳入的486名女性中,23名(4.7%)患者拒绝参与。在分析的463例患者中,平均年龄为47岁。386例(83.4%)患者选择乳房切除术。RT前的FCR水平报告为“无”(29.4%),“有一点”(51.2%),“一些”(12.1%)和“非常”(7.3%)。FCR严重程度的增加与中位焦虑评分升高(1.5、5.0、7.0、8.5)和临床显著性焦虑发生率升高(焦虑评分≥11;0%、3.4%、12.5%、26.5%)相关。同样,中位抑郁评分(2.0、4.0、6.0、6.5)随FCR严重程度升高,非典型抑郁(抑郁评分≥11;2.2%、3.4%、5.4%、17.7%)的患病率升高(均p < 0.001)。与参考“无”相比,FCR严重程度的每个单位增加与一类(“正常”、“边缘”和“异常”)焦虑增加(OR)分别为2.593 (p = 0.011)、5.889(< 0.001)和14.621(< 0.001)和抑郁增加(OR)分别为2.406(0.008)、3.045(0.009)和7.210(< 0.001)独立相关。FCR严重程度与大多数生活质量域呈负相关(p < 0.05)。结论:FCR是中国乳腺癌患者在放疗期间心理困扰和生活质量下降的重要因素。在这一人群中,应该优先进行焦虑和抑郁的常规筛查,并对FCR进行有针对性的干预。
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引用次数: 0
Adherence to Aromatase Inhibitor Therapy in Breast Cancer: Insights From a Multicenter Italian Study 坚持芳香化酶抑制剂治疗乳腺癌:来自意大利多中心研究的见解。
IF 2 4区 医学 Q3 OBSTETRICS & GYNECOLOGY Pub Date : 2025-12-19 DOI: 10.1155/tbj/8976679
Maria Agnese Fabbri, Alberto Fulvi, Matteo Vergati, Giuliana D’Auria, Patrizia Vici, Lorena Filomeno, Teresa Arcuri, Antonella Palazzo, Fabrizio Nelli, Cristina Fiore, Ilaria Portarena, Pina Tiziana Falbo, Rosalinda Rossi, Daniele Alesini, Valentina Sini, Roberta Pace, Patrizia Frittelli, Domenico Cristiano Corsi, Lucia Palombi, Simona Pisegna, Andrea Botticelli, Simone Scagnoli, Giorgio Pistillucci, Erica Giordani, Annalisa La Cesa

Background

In estrogen-receptor positive breast cancer (BC), oral adjuvant endocrine therapy (ET) administered for at least 5 years significantly reduces risks of disease recurrence and mortality. Among available therapies, aromatase inhibitors (AI) showed high efficacy. However, adherence to ET is very poor. Effective support by physicians requires the identification of factors influencing AI treatment adherence.

Materials and Methods

A prospective/retrospective multicentric study was conducted in adult BC women currently undergoing adjuvant treatment with AI. Study endpoints were assessed through a questionnaire after at least 12 months of adjuvant therapy. The primary objective was the assessment of the adherence to AI; secondary objectives were the assessment of adverse events (AEs) of the therapy and the solutions adopted for AEs.

Results

Overall, 903 patients with a median age of 63 years were enrolled. Two hundred and forty-three patients (26.9%) stated they do not respect the intake times. Adherence was not influenced by the number of drugs other than the ones for BC or by age. Most patients (87%) suffered from one or more AEs. The most frequent are musculoskeletal symptoms, which occurred in 86.2% of the patients. 74.5% and 74.4% of participants reported hot flashes and tiredness, respectively. No structured or uniform responses were reported regarding the strategy for solving side effects: answers were almost generic, but for more than 50% of patients, the final outcome was positive. AEs were a driver for nonadherence in only 19.6% of patients.

Conclusion

Survey results should be considered as an overview of AI therapy adherence in BC patients. We showed that the oncologist has a key role in improving therapeutic adherence and, as a consequence, in improving clinical outcome. Through a dialogue with the patient and a synergistic interaction with other clinical specialists, a greater awareness of the importance of the treatment could be warranted.

背景:在雌激素受体阳性乳腺癌(BC)中,口服辅助内分泌治疗(ET)给予至少5年可显著降低疾病复发和死亡率的风险。在现有的治疗方法中,芳香酶抑制剂(AI)显示出较高的疗效。然而,ET的依从性非常差。医生的有效支持需要确定影响人工智能治疗依从性的因素。材料和方法:对正在接受人工智能辅助治疗的成年BC女性进行了一项前瞻性/回顾性多中心研究。研究终点在至少12个月的辅助治疗后通过问卷进行评估。主要目的是评估对人工智能的依从性;次要目的是评估治疗的不良事件(ae)和采取的解决ae的方法。结果:总体而言,903例患者入组,中位年龄为63岁。243名患者(26.9%)表示不尊重服药时间。依从性不受除BC药物外的药物数量或年龄的影响。大多数患者(87%)遭受一种或多种不良事件。最常见的是肌肉骨骼症状,发生率为86.2%。74.5%和74.4%的参与者分别报告了潮热和疲劳。关于解决副作用的策略,没有结构化或统一的回答:答案几乎是通用的,但对于50%以上的患者,最终结果是积极的。不良事件是导致患者不依从的原因,仅占19.6%。结论:调查结果应被视为BC患者AI治疗依从性的概述。我们表明,肿瘤学家在提高治疗依从性方面发挥着关键作用,因此,在改善临床结果方面也发挥着关键作用。通过与患者的对话和与其他临床专家的协同互动,可以保证对治疗的重要性有更大的认识。
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引用次数: 0
Effectiveness of Duct Excision Procedures in Detecting Preneoplastic and Malignant Lesions in Pathological Nipple Discharge: A Retrospective Cohort Study 导管切除术在发现病理性乳头溢液癌前病变和恶性病变中的有效性:一项回顾性队列研究。
IF 2 4区 医学 Q3 OBSTETRICS & GYNECOLOGY Pub Date : 2025-12-15 DOI: 10.1155/tbj/2467046
Batuhan Ata, Volkan Karadağ, Kenan Çetin

Background and Aims

Nipple discharge ranges from benign to pathological, indicating inflammation or epithelial proliferation. In 5%–28% of cases, pathological nipple discharge (PND) may indicate breast carcinoma. Our objective was to evaluate the detection rates of malignant and high-risk lesions (HRL) in patients undergoing major duct excision (MDE) and microductectomy for diagnostic purposes due to PND and to assess the need for re-excision in malignancies.

Method

Patients diagnosed with PND between October 2015 and December 2023 underwent duct excision procedures after physical, imaging, and histopathological examinations, if necessary. Patients with malignancies detected by histopathological evaluation underwent oncological procedures and were excluded from the study.

Results

Among 118 patients, 80 underwent microductectomy and 38 underwent MDE. Intraductal lesions (ILs) were detected in 62% of cases, with higher detection rates in the microductectomy group (69% vs. 47%, p < 0.03). Of these lesions, 23 were classified as HRL (24% in the microductectomy group vs. 11% in the MDE group, p = 0.09). Malignancy was detected in 16 patients (13.6%), with a higher rate in the MDE group (18% vs. 11%, p = 0.3). Five patients required re-excision for clear surgical margins, with no significant difference between the groups (microductectomy: n = 2; MDE: n = 3, p = 0.3).

Conclusion

The malignancy detection rate was slightly higher in the MDE group; however, this difference was not statistically significant. Similarly, there was no significant difference in the need for re-excision. Microductectomy, which preserves lactation function, may be preferred for premenopausal individuals or those considering future pregnancies when clinical presentation supports single-duct involvement. The differing distribution of IL and HRL between procedures reflects the pathology associated with their respective clinical indications rather than a difference in diagnostic performance.

背景和目的:乳头溢液范围从良性到病理性,表明炎症或上皮增生。在5%-28%的病例中,病理性乳头溢液(PND)可能提示乳腺癌。我们的目的是评估因PND而接受主要导管切除术(MDE)和微导管切除术的患者的恶性和高危病变(HRL)的检出率,并评估恶性肿瘤再次切除的必要性。方法:2015年10月至2023年12月诊断为PND的患者在必要时经过物理、影像学和组织病理学检查后行导管切除术。通过组织病理学评估发现恶性肿瘤的患者接受肿瘤手术,并被排除在研究之外。结果:118例患者中,微导管切除术80例,MDE 38例。导管内病变(ILs)检出率为62%,微导管切除术组检出率更高(69% vs 47%, p p = 0.09)。恶性肿瘤16例(13.6%),MDE组发生率较高(18% vs. 11%, p = 0.3)。5例患者需要再次切除手术缘清晰,组间差异无统计学意义(微导管切除术:n = 2; MDE: n = 3, p = 0.3)。结论:MDE组恶性肿瘤检出率略高;然而,这种差异在统计学上并不显著。同样,再次切除的必要性也没有显著差异。微导管切除术,保留泌乳功能,可能更适合绝经前的个体或那些考虑未来怀孕的人,当临床表现支持单管受累性。不同手术之间IL和HRL的不同分布反映了与其各自临床适应症相关的病理,而不是诊断表现的差异。
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引用次数: 0
Examining the Role of Matrix Metalloproteinase-2 and MicroRNAs Regulation in Breast Cancer 基质金属蛋白酶-2和microrna调控在乳腺癌中的作用
IF 2 4区 医学 Q3 OBSTETRICS & GYNECOLOGY Pub Date : 2025-11-29 DOI: 10.1155/tbj/8816789
Elmira Aboutalebi Vand Beilankouhi, Niloufar Kheradi, Yosra Vaez-Gharamaleki, Salomeh Roshani, Sana Abbasi, Reza Safaralizadeh, Mohammad Valilo

Matrix metalloproteinase (MMPs) is a class of zinc-dependent enzymes that play an important role in the invasion and metastasis of cancer cells and have different types. MMP-2 is one of the important enzymes of this family. MicroRNAs (miRNAs) are noncoding RNAs that are involved in the regulation of gene expression of many enzymes and factors in the body. Emerging data have highlighted the relationship between MMP-2 and miRNAs. Studies have shown that miRNAs regulate MMP-2 by binding to the 3′ untranslated region (3′ UTR), which leads to a decrease or increase in MMP-2 expression and its enzymatic activity. For example, decreased expression of miR-106b leads to increased growth and invasion of breast cancer (BC) cells through increased expression of MMP-2. Therefore, understanding the regulatory mechanisms related to MMP-2 and miRNAs will provide new insights into the molecular pathways that drive BC progression and highlight potential therapeutic targets for the management of invasion and metastasis. Hence, in this study, we aimed to elucidate the relationship between MMP-2 and miRNAs in BC.

基质金属蛋白酶(Matrix metalloproteinase, MMPs)是一类锌依赖性酶,在癌细胞的侵袭和转移过程中起重要作用,具有不同的类型。MMP-2是该家族的重要酶之一。MicroRNAs (miRNAs)是非编码rna,参与调节体内许多酶和因子的基因表达。新出现的数据强调了MMP-2和mirna之间的关系。研究表明,mirna通过结合3 ' untranslation region (3 ' UTR)调控MMP-2,从而导致MMP-2表达和酶活性的降低或升高。例如,miR-106b表达的降低通过MMP-2表达的增加导致乳腺癌(BC)细胞的生长和侵袭增加。因此,了解与MMP-2和mirna相关的调控机制将为推动BC进展的分子途径提供新的见解,并为侵袭和转移的管理提供潜在的治疗靶点。因此,在本研究中,我们旨在阐明BC中MMP-2与mirna之间的关系。
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引用次数: 0
GSK-3β Regulates Tumor Stemness and Immune-Related Pathways in Triple-Negative Breast Cancer: A Bioinformatics and Experimental Validation Study GSK-3β调节三阴性乳腺癌的肿瘤干性和免疫相关通路:生物信息学和实验验证研究
IF 2 4区 医学 Q3 OBSTETRICS & GYNECOLOGY Pub Date : 2025-11-20 DOI: 10.1155/tbj/5943807
Ling Zhou, Xinyu Wang, Huiyin Zhu, Yang Chen, Lifen Bai, Chunyu Hu, Yuhan Wang, Mengfan Qi, Lu Yin, Jian Sun

Objective

Given the crucial roles of GSK-3β in epithelial–mesenchymal transition (EMT), we assume that it may also be involved in tumor stemness, immune evasion, and drug resistance in triple-negative breast cancer (TNBC). This study was designed to analyze the expression and clinical significance of GSK-3β and investigate its association with tumor stemness–related and immune-related genes.

Methods

GSK-3β expression and clinical data of TNBC patients were obtained from TCGA. Survival analysis, differential gene expression, and gene set enrichment analysis (GSEA) were performed to explore associations between GSK-3β and tumor stemness, immune response, and clinical outcomes in TNBC. Immune cell infiltration was assessed using xCell, and key GSK-3β-related proteins were validated via parallel reaction monitoring–based proteomics.

Results

GSK-3β expression was significantly upregulated in TNBC and was associated with poorer overall survival. In TNBC, 24 GSK-3β-associated genes linked to tumor stemness and immune response were identified, all of which were downregulated in the high GSK-3β expression group. Proteomic analysis further validated differential expression of key proteins, including upregulation of SERPINB2, KIT, and NOTCH1 and downregulation of DNMT1, MAPK1, and EP300 in GSK-3β-overexpressing cells.

Conclusion

GSK-3β overexpression was associated with poor prognosis and was found to influence tumor stemness, immune modulation, and key signaling pathways that drive tumor progression and therapeutic resistance.

目的考虑到GSK-3β在三阴性乳腺癌(TNBC)的上皮-间质转化(EMT)中的重要作用,我们推测GSK-3β也可能参与肿瘤的干性、免疫逃避和耐药。本研究旨在分析GSK-3β的表达及其临床意义,并探讨其与肿瘤干细胞相关基因和免疫相关基因的相关性。方法通过TCGA获取TNBC患者GSK-3β表达及临床资料。通过生存分析、差异基因表达和基因集富集分析(GSEA)来探索GSK-3β与TNBC肿瘤干性、免疫反应和临床结局之间的关系。使用xCell评估免疫细胞浸润,并通过基于平行反应监测的蛋白质组学验证关键gsk -3β相关蛋白。结果GSK-3β在TNBC中表达显著上调,并与较差的总生存率相关。在TNBC中,鉴定出24个与肿瘤干性和免疫应答相关的GSK-3β相关基因,这些基因在GSK-3β高表达组中均下调。蛋白质组学分析进一步证实了gsk -3β-过表达细胞中关键蛋白的差异表达,包括SERPINB2、KIT和NOTCH1的上调以及DNMT1、MAPK1和EP300的下调。结论GSK-3β过表达与不良预后相关,并影响肿瘤的干性、免疫调节以及驱动肿瘤进展和治疗耐药的关键信号通路。
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引用次数: 0
Correction to “Evaluating DNA Methylation in Random Fine Needle Aspirates from the Breast to Inform Cancer Risk” 对“评估随机乳腺细针抽吸物中的DNA甲基化以告知癌症风险”的更正
IF 2 4区 医学 Q3 OBSTETRICS & GYNECOLOGY Pub Date : 2025-11-15 DOI: 10.1155/tbj/9873020

K. Visvanathan, A. Cimino-Mathews, M. J. Fackler, et al., “Evaluating DNA Methylation in Random Fine Needle Aspirates from the Breast to Inform Cancer Risk,” The Breast Journal 2022 (2022): 9533461, https://doi.org/10.1155/2022/9533461.

In the article titled “Evaluating DNA Methylation in Random Fine Needle Aspirates from the Breast to Inform Cancer Risk,” there was an error in the Conflicts of Interest section. The corrected section appears below:

Conflicts of Interest

Kala Visvanathan reports funding from Cepheid and nonfinancial support from Optra Health Inc. Mary Jo Fackler reports grants from Cepheid and served as a Cepheid Consultant from February 2015 to February 2020. Mary Jo Fackler received license royalty fees from Cepheid from December 2014 through July 2021 for use of JHU cMethDNA and QM-MSP assays.

Saraswati Sukumar was awarded a grant from Cepheid and Kala Visvanathan and Mary Jo Fackler received support on it. Saraswati Sukumar served as Cepheid consultant from February 2015 through February 2020 and received license royalty fees from Cepheid (December 2014 through 2021) for use of JHU cMethDNA and QM-MSP patents. Mary Jo Fackler and Saraswati Sukumar are co-inventors of the cMethDNA assay, US patent US10450609B2. The JH Office of Policy is managing the COI for Saraswati Sukumar and Mary Jo Fackler. Vered Stearns received research grants to Johns Hopkins from Abbvie, Biocept, Novartis, Pfizer, Puma Biotechnology, and QUE. She served on the Oncology Advisory board for Novartis in 2021 and was Chair of a Data Safety Monitoring Board for AstraZeneca. She received nonfinancial support from Foundation Medicine for study assays.

We apologize for this error.

K. Visvanathan, A. ciminomathews, M. J. Fackler等,“评估随机乳腺细针抽吸器中的DNA甲基化以告知癌症风险”,《乳腺杂志》2022 (2022):9533461,https://doi.org/10.1155/2022/9533461.In文章标题为“评估随机乳腺细针抽吸器中的DNA甲基化以告知癌症风险”,在利益冲突部分有一个错误。更正后的部分如下:利益冲突kala Visvanathan报告了造父变星的资金和Optra Health Inc.的非财务支持。Mary Jo Fackler从2015年2月到2020年2月担任造父变星顾问。Mary Jo Fackler在2014年12月至2021年7月期间获得了仙王座JHU cMethDNA和QM-MSP检测的许可使用费。Saraswati Sukumar获得了造父变星的资助,Kala Visvanathan和Mary Jo Fackler也得到了支持。Saraswati Sukumar于2015年2月至2020年2月担任Cepheid顾问,并从Cepheid获得使用JHU cMethDNA和QM-MSP专利的许可使用费(2014年12月至2021年)。Mary Jo Fackler和Saraswati Sukumar是cMethDNA测定法的共同发明者,美国专利US10450609B2。JH政策办公室正在为Saraswati Sukumar和Mary Jo Fackler管理COI。从艾伯维、Biocept、诺华、辉瑞、彪马生物技术和QUE获得了约翰霍普金斯大学的研究资助。她于2021年担任Novartis肿瘤学顾问委员会成员,并担任AstraZeneca数据安全监测委员会主席。她的研究分析得到了基础医学的非经济支持。我们为这个错误道歉。
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引用次数: 0
Influence of HER2 Changes on Survival Outcomes After Neoadjuvant Chemotherapy in Peruvian Patients With Triple-Negative Breast Cancer 秘鲁三阴性乳腺癌患者新辅助化疗后HER2变化对生存结果的影响
IF 2 4区 医学 Q3 OBSTETRICS & GYNECOLOGY Pub Date : 2025-11-14 DOI: 10.1155/tbj/3770655
Zaida Morante, Yomali Ferreyra, Iris Otoya, Natalia Valdiviezo, Norma Huarcaya-Chombo, Gabriela Polo-Mendoza, Cindy Calle, Jessica Meza, Carlos Castañeda, Tatiana Vidaurre, Guillermo Valencia, Patricia Rioja, Hugo Fuentes, Silvia P. Neciosup, Henry L. Gomez

Background

Lack of human epidermal growth factor receptor 2 (HER2) expression limits targeted treatments for triple-negative breast cancer (TNBC). HER2 status changes after neoadjuvant chemotherapy (NAC) have been reported, but their impact on survival in Peruvian TNBC patients remains unexplored. Here, we aimed to assess HER2 status before and after NAC and its association with clinical characteristics, treatment response, and survival outcomes.

Methods

Our analysis included clinicopathological data from 159 TNBC patients diagnosed between 2015 and 2019 at the Instituto Nacional de Enfermedades Neoplásicas (Lima, Peru) who received NAC. Logistic regression was used to assess the association between HER2 status at diagnosis and pathological complete response (pCR). Cohen’s Kappa analysis evaluated the agreement between pre- and post-NAC HER2 status, while Kaplan–Meier analysis estimated the impact of HER2 changes on overall survival (OS) and disease-free survival (DFS)

Results

Among TNBC patients, 40.3% were HER2-low at diagnosis and 14.9% achieved pCR. Pretherapeutic HER2 status was not associated with pCR (OR = 1.4, 95% CI = 0.55–3.61, and p = 0.5). HER2 status remained unchanged in 62.8% of HER2-zero and 75.9% of HER2-low patients post-NAC, showing moderate concordance (Cohen’s kappa = 0.3418, p < 0.001). No significant OS improvements were observed in patients with HER2 transitions: HER2-zero/HER2-low (HR = 0.52, 95% CI = 0.22–1.24, and p = 0.14), HER2-low/HER2-zero (HR = 0.9, 95% CI = 0.34–2.40, and p = 0.8), or HER2-low/HER2-low (HR = 0.71, 95% CI = 0.34–1.49, and p = 0.4) compared with HER2-zero/HER2-zero. Similar findings were reported for DFS.

Conclusion

These findings suggest that HER2 status conversion may not be prognostic for patients with TNBC treated with neoadjuvant therapy.

人表皮生长因子受体2 (HER2)表达的缺乏限制了三阴性乳腺癌(TNBC)的靶向治疗。新辅助化疗(NAC)后HER2状态的改变已被报道,但其对秘鲁TNBC患者生存的影响仍未被探讨。在这里,我们旨在评估NAC前后的HER2状态及其与临床特征、治疗反应和生存结果的关系。方法:我们分析了2015年至2019年在秘鲁利马国立Enfermedades研究所Neoplásicas (Lima, Peru)诊断的159例接受NAC治疗的TNBC患者的临床病理数据。采用Logistic回归评估诊断时HER2状态与病理完全缓解(pCR)之间的关系。Cohen的Kappa分析评估了nac前和nac后HER2状态之间的一致性,Kaplan-Meier分析估计了HER2变化对总生存期(OS)和无病生存期(DFS)的影响。结果在TNBC患者中,40.3%在诊断时HER2低,14.9%达到pCR。治疗前HER2状态与pCR无关(OR = 1.4, 95% CI = 0.55-3.61, p = 0.5)。nac后,62.8%的HER2零和75.9%的HER2低患者的HER2状态保持不变,显示中度一致性(Cohen’s kappa = 0.3418, p < 0.001)。与HER2-zero/HER2-zero相比,HER2-zero/HER2-low (HR = 0.52, 95% CI = 0.22-1.24, p = 0.14)、HER2-low/HER2-zero (HR = 0.9, 95% CI = 0.34-2.40, p = 0.8)或HER2-low/HER2-low (HR = 0.71, 95% CI = 0.34-1.49, p = 0.4)患者的OS无显著改善。DFS也有类似的发现。结论这些发现提示HER2状态转换可能不是新辅助治疗TNBC患者的预后。
{"title":"Influence of HER2 Changes on Survival Outcomes After Neoadjuvant Chemotherapy in Peruvian Patients With Triple-Negative Breast Cancer","authors":"Zaida Morante,&nbsp;Yomali Ferreyra,&nbsp;Iris Otoya,&nbsp;Natalia Valdiviezo,&nbsp;Norma Huarcaya-Chombo,&nbsp;Gabriela Polo-Mendoza,&nbsp;Cindy Calle,&nbsp;Jessica Meza,&nbsp;Carlos Castañeda,&nbsp;Tatiana Vidaurre,&nbsp;Guillermo Valencia,&nbsp;Patricia Rioja,&nbsp;Hugo Fuentes,&nbsp;Silvia P. Neciosup,&nbsp;Henry L. Gomez","doi":"10.1155/tbj/3770655","DOIUrl":"https://doi.org/10.1155/tbj/3770655","url":null,"abstract":"<div>\u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Lack of human epidermal growth factor receptor 2 (HER2) expression limits targeted treatments for triple-negative breast cancer (TNBC). HER2 status changes after neoadjuvant chemotherapy (NAC) have been reported, but their impact on survival in Peruvian TNBC patients remains unexplored. Here, we aimed to assess HER2 status before and after NAC and its association with clinical characteristics, treatment response, and survival outcomes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Our analysis included clinicopathological data from 159 TNBC patients diagnosed between 2015 and 2019 at the Instituto Nacional de Enfermedades Neoplásicas (Lima, Peru) who received NAC. Logistic regression was used to assess the association between HER2 status at diagnosis and pathological complete response (pCR). Cohen’s Kappa analysis evaluated the agreement between pre- and post-NAC HER2 status, while Kaplan–Meier analysis estimated the impact of HER2 changes on overall survival (OS) and disease-free survival (DFS)</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Among TNBC patients, 40.3% were HER2-low at diagnosis and 14.9% achieved pCR. Pretherapeutic HER2 status was not associated with pCR (OR = 1.4, 95% CI = 0.55–3.61, and <i>p</i> = 0.5). HER2 status remained unchanged in 62.8% of HER2-zero and 75.9% of HER2-low patients post-NAC, showing moderate concordance (Cohen’s kappa = 0.3418, <i>p</i> &lt; 0.001). No significant OS improvements were observed in patients with HER2 transitions: HER2-zero/HER2-low (HR = 0.52, 95% CI = 0.22–1.24, and <i>p</i> = 0.14), HER2-low/HER2-zero (HR = 0.9, 95% CI = 0.34–2.40, and <i>p</i> = 0.8), or HER2-low/HER2-low (HR = 0.71, 95% CI = 0.34–1.49, and <i>p</i> = 0.4) compared with HER2-zero/HER2-zero. Similar findings were reported for DFS.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>These findings suggest that HER2 status conversion may not be prognostic for patients with TNBC treated with neoadjuvant therapy.</p>\u0000 </section>\u0000 </div>","PeriodicalId":56326,"journal":{"name":"Breast Journal","volume":"2025 1","pages":""},"PeriodicalIF":2.0,"publicationDate":"2025-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1155/tbj/3770655","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145522313","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Patient-Reported Outcomes After Same-Day Mastectomy Among Older Breast Cancer Patients: Results From a Prospective Clinical Trial 老年乳腺癌患者当天乳房切除术后患者报告的结果:一项前瞻性临床试验的结果
IF 2 4区 医学 Q3 OBSTETRICS & GYNECOLOGY Pub Date : 2025-11-07 DOI: 10.1155/tbj/9953747
Jessica C. Gooch, Qi Ying McClelland, Kathryn Paschalis, Maya Anand, Allison Magnuson, Jenna Dobbins, Kristin A. Skinner, Ann Olzinski-Kunze, Anna Weiss

Background

The safety and value of same-day mastectomy are well-documented but the patient perspective is underreported, especially among older patients. This study aimed to investigate older patient-reported recovery quality after mastectomy; we hypothesized that patients who were discharged same day would report better recovery.

Methods

A prospective trial included frailty screening and prehabilitation for patients age ≥ 65 undergoing mastectomy for breast cancer. Primary endpoint, same-day discharge rate, was previously reported and was significantly higher than the year prior. Secondary endpoint was patient-reported postoperative recovery quality, per the Quality of Recovery-15 measure (QoR-15; 15 questions scored 1–10, 10 being best). Patients responded by phone 24–72 h postdischarge. One-tailed T-tests compared responses between same-day and admitted patients.

Results

37/55 (67.3%) patients ≥ 65 who underwent unilateral/bilateral mastectomy for early-stage breast cancer responded. Mean age was 73.6 (standard deviation 7.6), most had invasive carcinoma (44, 80.0%), and mean 5-factor Modified Frailty Index (mFI-5) was 1.3 of 5 (standard deviation 0.9); nonresponders had similar characteristics. There were no significant differences in any QoR-15 item (all p > 0.05). In fact, most responses were very similar, different by only one-tenth of 1 point or identical. The following answers slightly (0.2 difference or more) numerically favored same-day discharge: feeling rested, having good sleep, less moderate pain, and freedom from feeling anxious or depressed. No items favored admission.

Conclusions

Although this trial was not powered for secondary analyses, it is clinically meaningful that older patients undergoing same-day mastectomy reported similar recovery quality as those admitted. Same-day mastectomy should be considered for older patients.

背景:当天乳房切除术的安全性和价值有充分的文献记录,但患者的观点被低估,特别是在老年患者中。本研究旨在调查老年患者报告的乳房切除术后的恢复质量;我们假设同一天出院的患者会报告更好的恢复。方法一项前瞻性试验,对年龄≥65岁的乳腺癌切除术患者进行虚弱筛查和康复治疗。主要终点,当日出院率,先前报道过,明显高于前一年。次要终点是患者报告的术后恢复质量,根据恢复质量-15测量(QoR-15; 15个问题得分为1 - 10,10为最好)。患者在出院后24-72小时通过电话回应。单尾t检验比较了当日和住院患者的反应。结果≥65岁的患者中,37/55(67.3%)的患者接受了单侧/双侧早期乳腺癌切除术。平均年龄73.6岁(标准差7.6),以浸润性癌居多(44,80.0%),5因素修正虚弱指数(mFI-5)平均为1.3 / 5(标准差0.9);无应答者也有类似的特征。QoR-15项无显著差异(p > 0.05)。事实上,大多数回答都非常相似,只有十分之一点的不同或相同。以下答案在数字上略微(相差0.2或更多)倾向于当天出院:感觉休息好,睡眠好,疼痛减轻,没有焦虑或抑郁的感觉。没有项目赞成入场。结论:虽然该试验没有进行二次分析,但接受同日乳房切除术的老年患者报告的恢复质量与入院患者相似,这在临床上具有意义。老年患者应考虑当天进行乳房切除术。
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引用次数: 0
Clinical Characteristics and Independent Risk Factors for Pathologic Nipple Discharge of 375 Cases 375例病理性乳头溢液的临床特点及独立危险因素分析
IF 2 4区 医学 Q3 OBSTETRICS & GYNECOLOGY Pub Date : 2025-10-28 DOI: 10.1155/tbj/6615296
Junyue Wang, Dongxiao Zhang, Qiao Huang, Na Fu, Wenjie Zhao, Yu Zhou, Yubo Guo, Xiaolong Xu, Yudong Li

Background

While the characteristics of pathologic nipple discharge (PND) are well documented in the literature, comparative clinical and risk factor analyses across different pathologic subtypes are lacking.

Methods

Medical records of patients with nipple discharge were retrospectively retrieved from an electronic medical record database and analyzed. In this study, 375 patients with a postoperative pathologically confirmed diagnosis of PND were included.

Results

Age serves as an important independent risk factor for precancerous lesions and breast cancer, with the median age increasing alongside the severity of the pathology. Individuals under 45 years of age predominantly exhibited non-neoplastic and benign neoplastic lesions, whereas those over 45 were more likely to have precancerous lesions or breast cancer, with statistical significance (p < 0.01). Discharge color was a significant factor in distinguishing between different pathological findings (p < 0.01). Discharge color serves as an important independent risk factor for breast cancer. Bloody discharge was associated with a significantly higher incidence of breast cancer and precancerous lesions compared to non-bloody discharges. Upon dividing bloody discharge into brown and bright red for in-depth analysis, no significant difference was observed among the different pathological types (p > 0.05). Ductoscopy has a higher diagnostic rate for breast cancer and precancerous lesions (p < 0.01).

Conclusion

These results suggest the clinical characteristics of PND patients across four pathological types: non-neoplastic lesions, benign neoplastic lesions, precancerous lesions, and breast cancer, at the same time emphasizing the importance of age and discharge color as independent risk factors in the prognosis and management of nipple discharge.

虽然病理性乳头溢液(PND)的特征在文献中有很好的记录,但缺乏不同病理亚型的比较临床和危险因素分析。方法对电子病历数据库中乳头溢液患者的病历进行回顾性分析。本研究纳入了375例术后病理确诊为PND的患者。结果年龄是癌前病变和乳腺癌的重要独立危险因素,年龄中位数随病理严重程度的增加而增加。45岁以下人群以非肿瘤性和良性肿瘤病变为主,45岁以上人群癌前病变和乳腺癌发生率较高,差异有统计学意义(p < 0.01)。分泌物颜色是区分不同病理表现的重要因素(p < 0.01)。分泌物颜色是乳腺癌的重要独立危险因素。与非血性分泌物相比,血性分泌物与乳腺癌和癌前病变的发生率显著升高有关。将带血分泌物分为棕色和鲜红色进行深入分析,不同病理类型间无显著差异(p > 0.05)。导管镜检查对乳腺癌及癌前病变的诊断率较高(p < 0.01)。结论乳头溢液患者具有非肿瘤性病变、良性肿瘤病变、癌前病变和乳腺癌四种病理类型的临床特征,同时强调年龄和溢液颜色作为独立危险因素对乳头溢液预后和处理的重要性。
{"title":"Clinical Characteristics and Independent Risk Factors for Pathologic Nipple Discharge of 375 Cases","authors":"Junyue Wang,&nbsp;Dongxiao Zhang,&nbsp;Qiao Huang,&nbsp;Na Fu,&nbsp;Wenjie Zhao,&nbsp;Yu Zhou,&nbsp;Yubo Guo,&nbsp;Xiaolong Xu,&nbsp;Yudong Li","doi":"10.1155/tbj/6615296","DOIUrl":"https://doi.org/10.1155/tbj/6615296","url":null,"abstract":"<div>\u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>While the characteristics of pathologic nipple discharge (PND) are well documented in the literature, comparative clinical and risk factor analyses across different pathologic subtypes are lacking.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Medical records of patients with nipple discharge were retrospectively retrieved from an electronic medical record database and analyzed. In this study, 375 patients with a postoperative pathologically confirmed diagnosis of PND were included.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Age serves as an important independent risk factor for precancerous lesions and breast cancer, with the median age increasing alongside the severity of the pathology. Individuals under 45 years of age predominantly exhibited non-neoplastic and benign neoplastic lesions, whereas those over 45 were more likely to have precancerous lesions or breast cancer, with statistical significance (<i>p</i> &lt; 0.01). Discharge color was a significant factor in distinguishing between different pathological findings (<i>p</i> &lt; 0.01). Discharge color serves as an important independent risk factor for breast cancer. Bloody discharge was associated with a significantly higher incidence of breast cancer and precancerous lesions compared to non-bloody discharges. Upon dividing bloody discharge into brown and bright red for in-depth analysis, no significant difference was observed among the different pathological types (<i>p</i> &gt; 0.05). Ductoscopy has a higher diagnostic rate for breast cancer and precancerous lesions (<i>p</i> &lt; 0.01).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>These results suggest the clinical characteristics of PND patients across four pathological types: non-neoplastic lesions, benign neoplastic lesions, precancerous lesions, and breast cancer, at the same time emphasizing the importance of age and discharge color as independent risk factors in the prognosis and management of nipple discharge.</p>\u0000 </section>\u0000 </div>","PeriodicalId":56326,"journal":{"name":"Breast Journal","volume":"2025 1","pages":""},"PeriodicalIF":2.0,"publicationDate":"2025-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1155/tbj/6615296","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145406903","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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