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Comparative Analysis of Women's Breast Cancer Survival Time at Three Selected Government Referral Hospitals in Ethiopia's Amhara Region Using Parametric Shared Frailty Models. 使用参数共享虚弱模型比较分析埃塞俄比亚阿姆哈拉地区三家选定政府转诊医院的妇女乳腺癌生存时间。
IF 2.6 4区 医学 Q2 Medicine Pub Date : 2024-05-29 eCollection Date: 2024-01-01 DOI: 10.2147/BCTT.S447684
Seid Fentaw, Anteneh Asmare Godana, Dawit Abathun, Dessie Melese Chekole

Background: One in five people will eventually develop cancer, and one in eleven women will lose their lives to the disease. The main aim of this study is to determinants of survival time of women with breast cancer using appropriate Frailty models.

Methods: A study involving 632 Ethiopian women with breast cancer was conducted between 2018 and 2020, utilizing medical records from Felege-Hiwot Referral Hospital, the University of Gondar, and Dessie Referral Hospital. To compare survival, the Kaplan-Meier plot (s) and Log rank test were employed; to assess mean survival, one-way analysis of variance and the t test were utilized. The factors influencing women's survival times from breast cancer were identified using the parametric shared frailty model and the accelerated failure time model.

Results: The median time to die for breast cancer patients treated at FHRH, UoGCSH, and DRH was 14.91 months, 11.14 months, and 12.32 months, respectively. The parametric model of shared frailty fit those who were statistically significant in univariate analysis. The results showed that survival of women with breast cancer was significantly influenced by age, tumor size, comorbidity, nodal status, stage, histologic grade, and type of primary treatment initiated. When comparing mean survival times between hospitals, the results showed a significant difference; patients who were treated in FHRH live significantly longer than patients treated in UoGCSH and DRH, whereas patients treated in UoGCSH have comparatively lower survival. Women with stage IV and comorbidities have 22.4% and 27.1% shorter expected survival, respectively.

Conclusion: This finding suggests that improving the availability and accessibility of radiation therapy and surgery, eliminating disparities between hospitals, raising awareness of early signs and symptoms of breast cancer and encouraging women to seek clinical help, and highlighting women with comorbidities at diagnosis are important ways to increase survival time.

背景:每五个人中就有一人最终会罹患癌症,每十一名妇女中就有一人会因癌症而丧生。本研究的主要目的是利用适当的虚弱模型确定乳腺癌女性患者的生存时间:2018年至2020年期间,利用Felege-Hiwot转诊医院、贡德尔大学和Dessie转诊医院的医疗记录,开展了一项涉及632名埃塞俄比亚女性乳腺癌患者的研究。为比较存活率,采用了卡普兰-梅耶图(s)和对数秩检验;为评估平均存活率,采用了单因素方差分析和 t 检验。使用参数共享虚弱模型和加速失败时间模型确定了影响妇女乳腺癌生存时间的因素:结果:在FHRH、UoGCSH和DRH接受治疗的乳腺癌患者的中位死亡时间分别为14.91个月、11.14个月和12.32个月。共同虚弱参数模型符合单变量分析中具有统计学意义的患者。结果表明,年龄、肿瘤大小、合并症、结节状态、分期、组织学分级和初治类型对乳腺癌妇女的生存期有显著影响。在比较不同医院的平均生存时间时,结果显示出明显的差异;在弗吉尼亚赫尔辛基医院接受治疗的患者的生存时间明显长于在格拉斯哥大学附属加利福尼亚医院和格拉斯哥大学医学院附属加利福尼亚医院接受治疗的患者,而在格拉斯哥大学附属加利福尼亚医院接受治疗的患者的生存时间则相对较短。IV期和合并症妇女的预期生存期分别缩短了22.4%和27.1%:这一结果表明,改善放射治疗和手术的可用性和可及性、消除医院之间的差异、提高对乳腺癌早期症状和体征的认识并鼓励妇女寻求临床帮助,以及在诊断时重点关注有合并症的妇女,是延长生存时间的重要途径。
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引用次数: 0
Does the Dose of Standard Adjuvant Chemotherapy Affect the Triple-negative Breast Cancer Benefit from Extended Capecitabine Metronomic Therapy? An Exploratory Analysis of the SYSUCC-001 Trial 标准辅助化疗的剂量会影响三阴性乳腺癌从卡培他滨延伸剂量组治疗中获益吗?SYSUCC-001试验的探索性分析
IF 2.6 4区 医学 Q2 Medicine Pub Date : 2024-04-12 DOI: 10.2147/BCTT.S447290
Ying Chen, Wen-Xia Li, Jia-Hua Wu, Geng-Hang Chen, Chun-Min Yang, Hai Lu, Xi Wang, Shu-sen Wang, Heng Huang, Li Cai, Li Zhao, Rou-Jun Peng, Ying Lin, Jun Tang, Jian Zeng, Le-hong Zhang, Y. Ke, Xian-Ming Wang, Xin-Mei Liu, An-Qin Zhang, Fei Xu, Xiwen Bi, Jiajia Huang, Ji-Bin Li, D. Pang, Cong Xue, Yan-Xia Shi, Zhenyu He, Huan-xin Lin, Xin An, W. Xia, Ye Cao, Yingwei Guo, R. Hong, Kui-Kui Jiang, Y. Zhong, Ge Zhang, P. Tienchaiananda, Masahiro Oikawa, Zhong-Yu Yuan, Qian-Jun Chen
Purpose Results from studies of extended capecitabine after the standard adjuvant chemotherapy in early stage triple-negative breast cancer (TNBC) were inconsistent, and only low-dose capecitabine from the SYSUCC-001 trial improved disease-free survival (DFS). Adjustment of the conventional adjuvant chemotherapy doses affect the prognosis and may affect the efficacy of subsequent treatments. This study investigated whether the survival benefit of the SYSUCC-001 trial was affected by dose adjustment of the standard adjuvant chemotherapy or not. Patients and Methods We reviewed the adjuvant chemotherapy regimens before the extended capecitabine in the SYSUCC-001 trial. Patients were classified into “consistent” (standard acceptable dose) and “inconsistent” (doses lower than acceptable dose) dose based on the minimum acceptable dose range in the landmark clinical trials. Cox proportional hazards model was used to investigate the impact of dose on the survival outcomes. Results All 434 patients in SYSUCC-001 trial were enrolled in this study. Most of patients administered the anthracycline-taxane regimen accounted for 88.94%. Among patients in the “inconsistent” dose, 60.8% and 47% received lower doses of anthracycline and taxane separately. In the observation group, the “inconsistent” dose of anthracycline and taxane did not affect DFS compared with the “consistent” dose. Moreover, in the capecitabine group, the “inconsistent” anthracycline dose did not affect DFS compared with the “consistent” dose. However, patients with “consistent” taxane doses benefited significantly from extended capecitabine (P=0.014). The sufficient dose of adjuvant taxane had a positive effect of extended capecitabine (hazard ratio [HR] 2.04; 95% confidence interval [CI] 1.02 to 4.06). Conclusion This study found the dose reduction of adjuvant taxane might negatively impact the efficacy of capecitabine. Therefore, the reduction of anthracycline dose over paclitaxel should be given priority during conventional adjuvant chemotherapy, if patients need dose reduction and plan for extended capecitabine.
目的 早期三阴性乳腺癌(TNBC)标准辅助化疗后延长卡培他滨的研究结果不一致,只有SYSUCC-001试验中的低剂量卡培他滨改善了无病生存期(DFS)。调整常规辅助化疗剂量会影响预后,并可能影响后续治疗的疗效。本研究探讨了SYSUCC-001试验的生存获益是否会受到标准辅助化疗剂量调整的影响。患者和方法 我们回顾了SYSUCC-001试验中延长卡培他滨疗程前的辅助化疗方案。根据具有里程碑意义的临床试验中的最小可接受剂量范围,将患者分为 "一致"(标准可接受剂量)和 "不一致"(剂量低于可接受剂量)两类。采用 Cox 比例危险模型研究剂量对生存结果的影响。结果 SYSUCC-001试验的所有434名患者都参加了本研究。大多数患者接受了蒽环类-他烷类疗法,占88.94%。在 "剂量不一致 "的患者中,分别有 60.8%和 47%的患者接受了较低剂量的蒽环类和紫杉类药物。在观察组中,与 "一致 "剂量相比,蒽环类和紫杉类药物的 "不一致 "剂量不会影响 DFS。此外,在卡培他滨组,与 "一致 "剂量相比,蒽环类药物剂量 "不一致 "不影响 DFS。然而,"一致 "紫杉类药物剂量的患者从延长的卡培他滨治疗中明显获益(P=0.014)。足够剂量的辅助类固醇对延长卡培他滨有积极影响(危险比[HR]2.04;95%置信区间[CI]1.02至4.06)。结论 本研究发现,减少辅助性紫杉类药物的剂量可能会对卡培他滨的疗效产生负面影响。因此,在常规辅助化疗期间,如果患者需要减量并计划延长卡培他滨的疗程,应优先考虑减少蒽环类药物的剂量而非紫杉醇。
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引用次数: 0
Identification and Validation of Novel Metastasis-Related Immune Gene Signature in Breast Cancer 乳腺癌转移相关免疫基因新特征的鉴定与验证
IF 2.6 4区 医学 Q2 Medicine Pub Date : 2024-04-01 DOI: 10.2147/BCTT.S448642
Shen Ma, Ran Hao, Yi-Wei Lu, Hui-Po Wang, Jie Hu, Yi-Xin Qi
Background Distant metastasis remains the leading cause of death among patients with breast cancer (BRCA). The process of cancer metastasis involves multiple mechanisms, including compromised immune system. However, not all genes involved in immune function have been comprehensively identified. Methods Firstly 1623 BRCA samples, including transcriptome sequencing and clinical information, were acquired from Gene Expression Omnibus (GSE102818, GSE45255, GSE86166) and The Cancer Genome Atlas-BRCA (TCGA-BRCA) dataset. Subsequently, weighted gene co-expression network analysis (WGCNA) was performed using the GSE102818 dataset to identify the most relevant module to the metastasis of BRCA. Besides, ConsensusClusterPlus was applied to divide TCGA-BRCA patients into two subgroups (G1 and G2). In the meantime, the least absolute shrinkage and selection operator (LASSO) regression analysis was used to construct a metastasis-related immune genes (MRIGs)_score to predict the metastasis and progression of cancer. Importantly, the expression of vital genes was validated through reverse transcription quantitative polymerase chain reaction (RT-qPCR) and immunohistochemistry (IHC). Results The expression pattern of 76 MRIGs screened by WGCNA divided TCGA-BRCA patients into two subgroups (G1 and G2), and the prognosis of G1 group was worse. Also, G1 exhibited a higher mRNA expression level based on stemness index score and Tumor Immune Dysfunction and Exclusion score. In addition, higher MRIGs_score represented the higher probability of progression in BRCA patients. It was worth mentioning that the patients in the G1 group had a high MRIGs_score than those in the G2 group. Importantly, the results of RT-qPCR and IHC demonstrated that fasciculation and elongation protein zeta 1 (FEZ1) and insulin-like growth factor 2 receptor (IGF2R) were risk factors, while interleukin (IL)-1 receptor antagonist (IL1RN) was a protective factor. Conclusion Our study revealed a prognostic model composed of eight immune related genes that could predict the metastasis and progression of BRCA. Higher score represented higher metastasis probability. Besides, the consistency of key genes in BRCA tissue and bioinformatics analysis results from mRNA and protein levels was verified.
背景远处转移仍然是乳腺癌(BRCA)患者死亡的主要原因。癌症转移过程涉及多种机制,包括免疫系统受损。然而,并非所有参与免疫功能的基因都已被全面鉴定。方法 首先从基因表达总库(GSE102818、GSE45255、GSE86166)和癌症基因组图谱-BRCA(TCGA-BRCA)数据集中获取了1623个BRCA样本,包括转录组测序和临床信息。随后,利用 GSE102818 数据集进行了加权基因共表达网络分析(WGCNA),以确定与 BRCA 转移最相关的模块。此外,还应用 ConsensusClusterPlus 将 TCGA-BRCA 患者分为两个亚组(G1 和 G2)。同时,利用最小绝对收缩和选择算子(LASSO)回归分析构建了转移相关免疫基因(MRIGs)_评分,以预测癌症的转移和进展。重要的是,重要基因的表达通过反转录定量聚合酶链反应(RT-qPCR)和免疫组化(IHC)进行了验证。结果 WGCNA 筛选出的 76 个 MRIGs 的表达模式将 TCGA-BRCA 患者分为两个亚组(G1 和 G2),G1 组的预后较差。同时,根据干性指数评分和肿瘤免疫功能障碍与排斥评分,G1 组的 mRNA 表达水平更高。此外,MRIGs_score越高,代表BRCA患者病情恶化的概率越高。值得一提的是,G1 组患者的 MRIGs_score 比 G2 组高。重要的是,RT-qPCR 和 IHC 的结果表明,束状和伸长蛋白 zeta 1(FEZ1)和胰岛素样生长因子 2 受体(IGF2R)是风险因素,而白细胞介素(IL)-1 受体拮抗剂(IL1RN)是保护因素。结论 我们的研究揭示了一个由八个免疫相关基因组成的预后模型,该模型可预测 BRCA 的转移和进展。得分越高,代表转移的可能性越大。此外,研究还验证了 BRCA 组织中关键基因的一致性以及 mRNA 和蛋白质水平的生物信息学分析结果。
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引用次数: 0
Serum HER2 Level Predicts Therapeutic Efficacy and Prognosis in Advanced Breast Cancer Patients [Letter] 血清 HER2 水平可预测晚期乳腺癌患者的疗效和预后 [信]
IF 2.6 4区 医学 Q2 Medicine Pub Date : 2024-04-01 DOI: 10.2147/BCTT.S472589
Febie Syahruddin, Prihantono, Mirna Muis
We have read the paper written by Shuling Wang et al about Serum HER2 Level Predicts Therapeutic Efficacy and Prognosis in Advanced Breast Cancer Patients. 1 Serum HER2 has changed the treatment paradigm for half of patients with advanced breast cancer, and HER2 is currently defined as an expression immunohistochemistry without amplification via in-situ hybridization and therefore remains a clinical challenge in the treatment of breast cancer. 2 The introduction of antibody drug conjugates (ADCs) targeting HER2 offers a new treatment option for female breast cancer patients (FBC) who exhibit low HER2 levels; however, there is no evidence to show that low serum HER2 represents a new subtype of FBC; therefore, research is still needed to determine the impact of serum HER2 levels on breast cancer. 3 A study conducted by Shuling Wang et al analyzed sHER2 levels from 200 advanced breast cancer patients who received first or second-line treatment. Indicators of therapeutic efficacy and prognosis were objective response rate (ORR), disease control rate (DCR), and time to progression (TTP). 1 The indicator used is effective for the purposes of this study, however several other studies measure HER2 expression based on DNA, mRNA and protein tests which will most likely optimize HER2 testing with the aim of providing targeted therapy for patients who will benefit, while limiting exposure to treatment and toxicity, given that HER2 low breast cancer does not appear to represent a distinct breast cancer subtype then commonly used biomarkers and treatments should be
我们阅读了王淑玲等人撰写的关于血清 HER2 水平预测晚期乳腺癌患者疗效和预后的论文。1 血清 HER2 改变了半数晚期乳腺癌患者的治疗模式,目前 HER2 的定义是通过原位杂交免疫组化表达而不扩增,因此仍是乳腺癌治疗的临床难题。2 以 HER2 为靶点的抗体药物结合物(ADC)的问世为 HER2 水平较低的女性乳腺癌患者(FBC)提供了一种新的治疗选择;然而,目前尚无证据表明血清 HER2 水平较低代表了 FBC 的一种新亚型;因此,仍需开展研究以确定血清 HER2 水平对乳腺癌的影响。3 王淑玲等人的一项研究分析了 200 名接受一线或二线治疗的晚期乳腺癌患者的 sHER2 水平。疗效和预后指标为客观反应率(ORR)、疾病控制率(DCR)和进展时间(TTP)。1 本研究中使用的指标是有效的,但其他几项研究根据 DNA、mRNA 和蛋白质检测来测量 HER2 表达,这很可能会优化 HER2 检测,目的是为受益患者提供靶向治疗,同时限制治疗暴露和毒性。
{"title":"Serum HER2 Level Predicts Therapeutic Efficacy and Prognosis in Advanced Breast Cancer Patients [Letter]","authors":"Febie Syahruddin, Prihantono, Mirna Muis","doi":"10.2147/BCTT.S472589","DOIUrl":"https://doi.org/10.2147/BCTT.S472589","url":null,"abstract":"We have read the paper written by Shuling Wang et al about Serum HER2 Level Predicts Therapeutic Efficacy and Prognosis in Advanced Breast Cancer Patients. 1 Serum HER2 has changed the treatment paradigm for half of patients with advanced breast cancer, and HER2 is currently defined as an expression immunohistochemistry without amplification via in-situ hybridization and therefore remains a clinical challenge in the treatment of breast cancer. 2 The introduction of antibody drug conjugates (ADCs) targeting HER2 offers a new treatment option for female breast cancer patients (FBC) who exhibit low HER2 levels; however, there is no evidence to show that low serum HER2 represents a new subtype of FBC; therefore, research is still needed to determine the impact of serum HER2 levels on breast cancer. 3 A study conducted by Shuling Wang et al analyzed sHER2 levels from 200 advanced breast cancer patients who received first or second-line treatment. Indicators of therapeutic efficacy and prognosis were objective response rate (ORR), disease control rate (DCR), and time to progression (TTP). 1 The indicator used is effective for the purposes of this study, however several other studies measure HER2 expression based on DNA, mRNA and protein tests which will most likely optimize HER2 testing with the aim of providing targeted therapy for patients who will benefit, while limiting exposure to treatment and toxicity, given that HER2 low breast cancer does not appear to represent a distinct breast cancer subtype then commonly used biomarkers and treatments should be","PeriodicalId":9106,"journal":{"name":"Breast Cancer : Targets and Therapy","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140785062","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Therapy for Hormone Receptor-Positive, Human Epidermal Growth Receptor 2-Negative Metastatic Breast Cancer Following Treatment Progression via CDK4/6 Inhibitors: A Literature Review 通过 CDK4/6 抑制剂治疗激素受体阳性、人类表皮生长受体 2 阴性、治疗进展后的转移性乳腺癌:文献综述
IF 2.6 4区 医学 Q2 Medicine Pub Date : 2024-04-01 DOI: 10.2147/BCTT.S438366
Meixi Ye, Hao Xu, Jinhuan Ding, Li Jiang
Abstract Endocrine therapy (ET) with a cyclin-dependent kinase 4/6 inhibitor (CDK4/6i) is currently the first-line standard treatment for most patients with hormone receptor-positive (HR+) and human epidermal growth receptor 2-negative (HER2-) metastatic or advanced breast cancer. However, the majority of tumors response to and eventually develop resistance to CDK4/6is. The mechanisms of resistance are poorly understood, and the optimal postprogression treatment regimens and their sequences continue to evolve in the rapidly changing treatment landscape. In this review, we generally summarize the mechanisms of resistance to CDK4/6is and ET, and describe the findings from clinical trials using small molecule inhibitors, antibody-drug conjugates and immunotherapy, providing insights into how these novel strategies may reverse treatment resistance, and discussing how some have not translated into clinical benefit. Finally, we provide rational treatment strategies based on the current emerging evidence.
摘要 使用细胞周期蛋白依赖性激酶4/6抑制剂(CDK4/6i)进行内分泌治疗(ET)是目前大多数激素受体阳性(HR+)和人类表皮生长受体2阴性(HER2-)转移性或晚期乳腺癌患者的一线标准治疗方法。然而,大多数肿瘤会对 CDK4/6is 产生反应并最终产生耐药性。耐药机制尚不清楚,最佳的进展后治疗方案及其顺序也在快速变化的治疗环境中不断发展。在这篇综述中,我们概括了 CDK4/6is 和 ET 的耐药机制,描述了使用小分子抑制剂、抗体药物共轭物和免疫疗法的临床试验结果,深入探讨了这些新策略如何逆转耐药性,并讨论了其中一些策略如何未能转化为临床获益。最后,我们将根据目前新出现的证据提供合理的治疗策略。
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引用次数: 0
Serum HER2 Level Predicts Therapeutic Efficacy and Prognosis in Advanced Breast Cancer Patients 血清 HER2 水平可预测晚期乳腺癌患者的疗效和预后
IF 2.6 4区 医学 Q2 Medicine Pub Date : 2024-04-01 DOI: 10.2147/BCTT.S449510
Shuling Wang, Yuqin Chen, Weidong Li, Chun-fang Hao, Li Zhang, Wei-peng Zhao, Yehui Shi, Zhongsheng Tong
Background The purpose of this study was to investigate the therapeutic efficacy and prognosis of serum HER2 (sHER2) in patients with advanced breast cancer. Methods We analyzed the sHER2 levels of 200 patients with advanced breast cancer receiving first or second line treatment, the tissue HER2 (tHER2) level was also analyzed. Indicators of therapeutic efficacy and prognosis were objective response rate (ORR), disease control rate (DCR), and time to progression (TTP). Results The baseline sHER2 level was high in 132 patients and low in 68 patients. The high level of sHER2 is correlated with molecular subtype (p=0.016), visceral metastasis (p<0.001), liver metastasis (p<0.001), tissue HER-2 (tHER2) (p=0.001), and, among tHER2-low tumors (59 patients), the baseline sHER2 high level was associated with a higher proportion of brain metastasis. The ORR of patients with baseline sHER2 high level is higher than those with baseline sHER2 low level (p=0.026). The TTP of patients with baseline sHER2 low level is longer than the patients with baseline sHER2 high level (p=0.024). For patients with baseline sHER2 high level, a significant decrease in sHER2 after two cycles of treatment indicates higher ORR, DCR, and an extension of TTP. After multiple cycles of treatment, for patients with tHER-2 positive and baseline sHER2 high level, the DCR in the sHER2 decrease in the negative group was higher than that in the continuous positive group (p=0.037). Patients with a rapid decline type of sHER2 dynamic change curve had higher ORR and prolonged TTP compared with patients with other types of sHER2 dynamic change curve. There is no correlation between OS and sHER2 levels. Conclusion Our study showed that patients with advanced breast cancer had a high level of sHER2 at recurrence, regardless of whether they are tHER2 positive or negative. Dynamic detection of sHER2 can help predict therapeutic efficacy and prognosis, regardless of whether tHER-2 is positive or negative.
背景 本研究旨在探讨晚期乳腺癌患者血清 HER2(sHER2)的疗效和预后。方法 我们分析了 200 名接受一线或二线治疗的晚期乳腺癌患者的 sHER2 水平,同时还分析了组织 HER2(tHER2)水平。疗效和预后指标包括客观反应率(ORR)、疾病控制率(DCR)和进展时间(TTP)。结果 132 例患者的 sHER2 基线水平较高,68 例患者的水平较低。sHER2高水平与分子亚型(p=0.016)、内脏转移(p<0.001)、肝转移(p<0.001)、组织HER-2(tHER2)(p=0.001)相关,在tHER2低水平肿瘤(59例患者)中,基线sHER2高水平与脑转移比例较高相关。基线sHER2高水平患者的ORR高于基线sHER2低水平患者(p=0.026)。基线sHER2水平低的患者的TTP比基线sHER2水平高的患者长(p=0.024)。对于基线 sHER2 水平高的患者,治疗两个周期后 sHER2 水平显著下降,表明 ORR、DCR 和 TTP 延长。多周期治疗后,对于tHER-2阳性且基线sHER2水平高的患者,阴性组sHER2下降的DCR高于持续阳性组(P=0.037)。与其他类型的sHER2动态变化曲线相比,sHER2动态变化曲线快速下降型患者的ORR更高,TTP更长。OS 与 sHER2 水平之间没有相关性。结论 我们的研究表明,晚期乳腺癌患者无论 tHER2 阳性还是阴性,复发时的 sHER2 水平都很高。无论 tHER2 是阳性还是阴性,动态检测 sHER2 都有助于预测疗效和预后。
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引用次数: 0
HER2 Low Expression in Primary Male Breast Cancer. 原发性男性乳腺癌中的 HER2 低表达。
IF 2.6 4区 医学 Q2 Medicine Pub Date : 2024-03-28 eCollection Date: 2024-01-01 DOI: 10.2147/BCTT.S450682
Katleen Nobbe, Melanie Erices-Leclercq, Frank Foerster, Robert Förster, Stephan E Baldus, Christian Rudlowski, Lars Schröder, Sabine Lubig

Purpose: The introduction of HER2-targeting antibody drug conjugates (ADCs) offers new treatment options for female breast cancer patients (FBC) expressing low levels of HER2 (HER2 low). No evidence was found that HER2 low describes a new FBC subtype. There is a lack of studies determining the impact of HER2 low in male breast cancer (MBC). In this study, we evaluate the prevalence of HER2 low in primary MBC and correlate the results with patient characteristics.

Patients and methods: In this study, histological specimens were obtained from 120 male patients diagnosed and treated for primary invasive breast cancer from 1995 to 2022 at Breast Cancer Units in Bergisch Gladbach, Chemnitz, and Zwickau, Germany. HER2 immunostaining and in situ hybridization were performed by central pathology and evaluated based on the ASCO/CAP guidelines. The correlation of expression of HER2 low with tumor biological characteristics and patient outcomes was investigated.

Results: Out of all cases, four patients (3.3%) showed HER2 positivity (3+), 39 (32.5%) patients were classified as HER2 low, 7 (5.8%) were HER2 2+ (no amplification), 32 (26.7%) were HER2 1+, and 77 (64.2%) were classified as HER2 zero. Out of 77 HER2 zero cases, 47 tumors (61.0%) showed incomplete staining, with <10% of tumor cells classified as HER2 ultralow. No statistical correlation between HER2 low and tumor biological characteristics and patients' survival was found.

Conclusion: Our findings show a notable, albeit lower, prevalence of HER2 low expression in primary MBC. However, tumors expressing HER2 low do not show specific tumor biological features to define a new breast cancer subtype in MBC. Our results suggest that a significant number of MBC patients could benefit from ADCs, as shown in FBC. Further studies are required to better understand HER2 low breast cancer, both generally and in MBC.

目的:HER2 靶向抗体药物共轭物(ADC)的问世为表达低水平 HER2(HER2 低)的女性乳腺癌患者(FBC)提供了新的治疗选择。目前还没有证据表明 HER2 低表达是一种新的 FBC 亚型。目前还缺乏确定 HER2 低水平对男性乳腺癌(MBC)影响的研究。在本研究中,我们评估了原发性 MBC 中 HER2 低的流行率,并将结果与患者特征相关联:在这项研究中,我们从 1995 年至 2022 年期间在德国贝吉施格拉德巴赫、开姆尼茨和茨维考的乳腺癌科诊断和治疗原发性浸润性乳腺癌的 120 名男性患者身上获取了组织学标本。HER2 免疫染色和原位杂交由中心病理科进行,并根据 ASCO/CAP 指南进行评估。研究了HER2低表达与肿瘤生物学特征和患者预后的相关性:在所有病例中,4 例患者(3.3%)HER2 阳性(3+),39 例患者(32.5%)HER2 低表达,7 例患者(5.8%)HER2 2+(无扩增),32 例患者(26.7%)HER2 1+,77 例患者(64.2%)HER2 零表达。在 77 个 HER2 为零的病例中,47 个肿瘤(61.0%)显示为不完全染色,结论是:我们的研究结果表明,在原发性 MBC 中,HER2 低表达的发生率明显较低。然而,HER2 低表达的肿瘤并未显示出特定的肿瘤生物学特征,因此无法定义 MBC 中的一种新的乳腺癌亚型。我们的研究结果表明,大量的 MBC 患者可以从 ADCs 中获益,就像在 FBC 中显示的那样。要更好地了解HER2低表达乳腺癌(包括一般乳腺癌和MBC),还需要进一步的研究。
{"title":"HER2 Low Expression in Primary Male Breast Cancer.","authors":"Katleen Nobbe, Melanie Erices-Leclercq, Frank Foerster, Robert Förster, Stephan E Baldus, Christian Rudlowski, Lars Schröder, Sabine Lubig","doi":"10.2147/BCTT.S450682","DOIUrl":"10.2147/BCTT.S450682","url":null,"abstract":"<p><strong>Purpose: </strong>The introduction of HER2-targeting antibody drug conjugates (ADCs) offers new treatment options for female breast cancer patients (FBC) expressing low levels of HER2 (HER2 low). No evidence was found that HER2 low describes a new FBC subtype. There is a lack of studies determining the impact of HER2 low in male breast cancer (MBC). In this study, we evaluate the prevalence of HER2 low in primary MBC and correlate the results with patient characteristics.</p><p><strong>Patients and methods: </strong>In this study, histological specimens were obtained from 120 male patients diagnosed and treated for primary invasive breast cancer from 1995 to 2022 at Breast Cancer Units in Bergisch Gladbach, Chemnitz, and Zwickau, Germany. HER2 immunostaining and in situ hybridization were performed by central pathology and evaluated based on the ASCO/CAP guidelines. The correlation of expression of HER2 low with tumor biological characteristics and patient outcomes was investigated.</p><p><strong>Results: </strong>Out of all cases, four patients (3.3%) showed HER2 positivity (3+), 39 (32.5%) patients were classified as HER2 low, 7 (5.8%) were HER2 2+ (no amplification), 32 (26.7%) were HER2 1+, and 77 (64.2%) were classified as HER2 zero. Out of 77 HER2 zero cases, 47 tumors (61.0%) showed incomplete staining, with <10% of tumor cells classified as HER2 ultralow. No statistical correlation between HER2 low and tumor biological characteristics and patients' survival was found.</p><p><strong>Conclusion: </strong>Our findings show a notable, albeit lower, prevalence of HER2 low expression in primary MBC. However, tumors expressing HER2 low do not show specific tumor biological features to define a new breast cancer subtype in MBC. Our results suggest that a significant number of MBC patients could benefit from ADCs, as shown in FBC. Further studies are required to better understand HER2 low breast cancer, both generally and in MBC.</p>","PeriodicalId":9106,"journal":{"name":"Breast Cancer : Targets and Therapy","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10984208/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140334659","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
Amplifying Immune Responses: Microparticulate Vaccine Approach Against Breast Cancer. 放大免疫反应:微粒子疫苗防治乳腺癌。
IF 2.6 4区 医学 Q2 Medicine Pub Date : 2024-03-28 eCollection Date: 2024-01-01 DOI: 10.2147/BCTT.S441368
Michelle Marie Ubowski, Ryan VanSice, Morgan Marriott, Matthew J Yacobucci, Lipika Chablani

Introduction: The study focuses on evaluating the immune responses generated by a novel microparticulate murine breast cancer vaccine.

Methods: The methodology included the use of a co-culture model of dendritic cells (DCs), and T-cells to evaluate the immunotherapeutic responses generated by the vaccine.

Results: The study observed that the dendritic cells expressed significantly higher levels of MHC I, MHC II, CD 40, and CD 80 cell surface markers in the presence of the vaccine microparticles than the controls (p<0.05). This response was potentiated in the presence of an adjuvant, Poly (I:C). The study also demonstrated that the vaccine microparticles do not elicit inflammatory (TNF-alpha, IFN-gamma, IL-2, and IL-12) or immunosuppressive (IL-10) cytokine production when compared to the control.

Discussion: In conclusion, the study established the role of DCs in stimulating the cancer vaccine's adaptive immune responses.

简介:本研究的重点是评估新型微粒子小鼠乳腺癌疫苗产生的免疫反应:研究重点是评估一种新型微粒子小鼠乳腺癌疫苗产生的免疫反应:方法:使用树突状细胞(DC)和 T 细胞的共培养模型来评估疫苗产生的免疫治疗反应:结果:研究观察到,树突状细胞在疫苗微颗粒存在的情况下表达的 MHC I、MHC II、CD 40 和 CD 80 细胞表面标记物水平明显高于对照组(p 讨论:总之,这项研究确定了直流电在刺激癌症疫苗适应性免疫反应中的作用。
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引用次数: 0
ZNF217 Gene Copy Number as a Marker of Response to Standard Therapy Drugs According to ERα Status in Breast Cancer. 根据乳腺癌ERα状态将ZNF217基因拷贝数作为标准治疗药物反应的标记物
IF 2.6 4区 医学 Q2 Medicine Pub Date : 2024-03-15 eCollection Date: 2024-01-01 DOI: 10.2147/BCTT.S445753
Nelson Rangel, Iris Lorena Sánchez, Duván Sebastián Valbuena, Milena Rondón-Lagos

Purpose: The therapeutic decision for the management of breast cancer (BC) patients is based on the evaluation of prognostic factors alongside clinical and pathological parameters. Despite the use of standard biomarkers, response and resistance to therapy represent a challenge for clinicians. Among the new potential biomarkers for BC the ZNF217 gene have gained importance in recent years. However, while associations between ZNF217 gene copy number and clinicopathological characteristics have been established, its correlation with treatment response remains unclear.

Patients and methods: This study aimed to evaluate the ZNF217 gene copy number and establish its associations with treatment response in estrogen receptor positive (ERα+) and ERα negative (ERα-) BC cell lines. In addition, a validation of the relationship between ZNF217 gene copy number and its prognostic value was performed using datasets of BC patients retrieved from the cBioPortal public database.

Results: Our data show that in ERα+ cells, ZNF217 gene copy number increase (amplification), while cell proliferation decreases in response to standard drug treatments. In contrast, both ZNF217 gene copy number (gain) and cell proliferation increases in response to standard drug treatments in ERα- cells. The results obtained align with findings from the cBioPortal database analysis, demonstrating that ERα+/HER2- low proliferation patients, exhibiting ZNF217 gene amplification or gain, have a significantly higher survival probability after treatment, compared to ERα-/HER2- and HER2+ patients.

Conclusion: Our results suggest that in ERα+ BC cells, ZNF217 gene amplification could be indicative of a favorable response, while in ERα- BC cells, ZNF217 gene gain could be postulated as a potential predictor of treatment resistance. A broader understanding of the role of ZNF217 gene in treatment response, together with prospective studies in BC patients, could contribute to confirming our data, as well as optimizing existing treatments and exploring novel approaches to improve overall cancer treatment outcomes.

目的:乳腺癌(BC)患者的治疗决策基于对预后因素以及临床和病理参数的评估。尽管使用了标准生物标志物,但治疗反应和耐药性仍是临床医生面临的挑战。近年来,ZNF217 基因已成为治疗乳腺癌的新的潜在生物标志物。然而,虽然ZNF217基因拷贝数与临床病理特征之间的关系已经确定,但其与治疗反应的相关性仍不清楚:本研究旨在评估雌激素受体阳性(ERα+)和ERα阴性(ERα-)BC细胞系的ZNF217基因拷贝数,并确定其与治疗反应的相关性。此外,我们还利用从 cBioPortal 公共数据库中检索到的 BC 患者数据集验证了 ZNF217 基因拷贝数与其预后价值之间的关系:结果:我们的数据显示,在ERα+细胞中,ZNF217基因拷贝数增加(扩增),而细胞增殖在标准药物治疗下减少。相反,在ERα-细胞中,ZNF217基因拷贝数(增殖)和细胞增殖在标准药物治疗下都会增加。研究结果与cBioPortal数据库的分析结果一致,表明与ERα-/HER2和HER2+患者相比,出现ZNF217基因扩增或增益的ERα+/HER2-低增殖患者治疗后的生存概率明显更高:我们的研究结果表明,在ERα+ BC细胞中,ZNF217基因扩增可能预示着有利的反应,而在ERα- BC细胞中,ZNF217基因增殖可能被认为是耐药性的潜在预测因素。更广泛地了解ZNF217基因在治疗反应中的作用,并对BC患者进行前瞻性研究,将有助于证实我们的数据,并优化现有的治疗方法,探索新的方法来改善癌症的整体治疗效果。
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引用次数: 0
The Role of Ki-67 in HR+/HER2- Breast Cancer: A Real-World Study of 956 Patients. Ki-67在HR+/HER2-乳腺癌中的作用:一项针对 956 例患者的真实世界研究。
IF 2.6 4区 医学 Q2 Medicine Pub Date : 2024-03-08 eCollection Date: 2024-01-01 DOI: 10.2147/BCTT.S451617
Qin Ma, Yao-Bang Liu, Tong She, Xin-Lan Liu

Objective: This study determined the cut-off value of Ki-67 expression and discussed the interaction between Ki-67 and histological grade, further explored the prognostic role of Ki-67 in hormone receptor-positive and human epidermal growth factor receptor 2 negative (HR+/HER2-) breast cancer;.

Materials and methods: We assessed the Ki-67 expression of 956 patients with HR+/HER2 breast cancer diagnosed in the General Hospital of Ningxia Medical University from 2015 to 2019 by immunohistochemistry (IHC), The disease-free survival (DFS) was defined as the time from postoperative to the first local recurrence, distant metastasis or death of the disease. The follow-up by means of inpatient or outpatient medical records and telephone.

Results: 22.5% was used as the cut-off for low/high Ki-67 expression in HR+/HER2- breast cancer. Compared with the value of 14%, which is commonly used in clinic at present, the consistency of the two values is moderate (Kappa = 0.484, P<0.001). The expression of Ki-67 was increased with the grade. (Median: G1:10%; G2:20%; G3:40%. Mean: G1:13%; G2:23%; G3:39%, P <0.001). Survival analysis was based on all patients for a median of 51 months (24-89 months), 63 cases had recurrence or metastasis during the follow-up, which 21 cases had low expression of Ki-67 and 42 cases had high expression. The patients with Ki-67 ≥ 22.5% had a 2.969 higher risk of early recurrence and metastasis than the patients with Ki-67 < 22.5%. There were 4 cases of local recurrence, 7 cases of regional lymph node metastasis, and 52 cases of distant metastasis in all patients, the common distant metastases were bone, liver, and lung, and rare metastases were adrenal gland, bone marrow, and pericardium.

Conclusion: In HR+/HER2- breast cancer, patients with Ki-67 > 22.5% have a worse prognosis and are more likely to have early recurrence and metastasis.

研究目的本研究确定了Ki-67表达的临界值,探讨了Ki-67与组织学分级之间的相互作用,进一步探讨了Ki-67在激素受体阳性和人表皮生长因子受体2阴性(HR+/HER2-)乳腺癌中的预后作用;材料与方法:我们通过免疫组化(IHC)评估了2015年至2019年在宁夏医科大学总医院确诊的956例HR+/HER2乳腺癌患者的Ki-67表达情况,无病生存期(DFS)定义为从术后到疾病首次局部复发、远处转移或死亡的时间。结果:HR+/HER2-乳腺癌中 Ki-67 低/高表达的临界值为 22.5%。与目前临床上常用的 14% 的数值相比,两个数值的一致性适中(Kappa = 0.484,PP 结论):在HR+/HER2-乳腺癌中,Ki-67>22.5%的患者预后较差,更容易出现早期复发和转移。
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引用次数: 0
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Breast Cancer : Targets and Therapy
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