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Subcutaneous Trastuzumab: An Observational Study of Safety and Tolerability in Patients With Early HER2-Positive Breast Cancer. 皮下注射曲妥珠单抗:早期 HER2 阳性乳腺癌患者安全性和耐受性观察研究
IF 1.6 Q4 ONCOLOGY Pub Date : 2024-06-22 eCollection Date: 2024-01-01 DOI: 10.1155/2024/9551710
Iris Otoya, Natalia Valdiviezo, Zaida Morante, Cindy Calle, Yomali Ferreyra, Norma Huarcaya-Chombo, Gabriela Polo-Mendoza, Carlos Castañeda, Tatiana Vidaurre, Silvia P Neciosup, Mónica J Calderón, Henry L Gomez

Purpose: In Peru, breast cancer (BC) stands as the most predominant malignancy neoplasm among women. Trastuzumab has marked a significant milestone in the management of this disease. It has been shown to improve prognosis in human epidermal growth factor receptor 2 (HER2)-expressing female patients, but its repercussions and efficacy are yet to be analyzed in a context with limited resources. Methods: The study population is made of woman patients aged 18 years and older diagnosed with HER2-positive BC at Instituto Nacional de Enfermedades Neoplásicas (INEN, Lima, Peru) during 2019-2021 and treated with at least one dose of subcutaneous trastuzumab. We reviewed medical records to register treatment characteristics, adverse events (AEs), disease progression, and survival status. We considered a median follow-up time of 36 and 45 months for progression and survival status. Results: The majority of patients were over 50 years old (54.29%). Tumor size averaged 19.7 ± 16.1 mm. Lymph nodes were present in 44.78% of patients. Most patients received adjuvant chemotherapy (63.8%) as first-line treatment. Descriptive analyses of treatment outcomes revealed a 30% toxicity rate, primarily attributed to arthralgia (47.62%), followed by diarrhea, fatigue, and injection site reactions, with relatively lower discontinuation rates compared to larger scale studies. Differences in demographic, clinical, and treatment characteristics were not statistically significant concerning the emergence of AEs (p > 0.05). Progression appeared in nine patients, and the overall survival (OS) rate stood at 98.6% and 92.8%, respectively, during a median follow-up of 36 and 45 months. Conclusion: The research suggests that subcutaneous trastuzumab is comparable in effectiveness and safety to the intravenous administration. Regional-specific studies may provide valuable insights into demographic factors influencing treatment outcomes in Peru or other countries. Furthermore, it could represent a more accessible alternative, potentially enhancing patient adherence and optimizing healthcare resource logistics.

目的:在秘鲁,乳腺癌(BC)是女性最主要的恶性肿瘤。曲妥珠单抗是治疗这种疾病的一个重要里程碑。事实证明,它能改善表达人类表皮生长因子受体 2(HER2)的女性患者的预后,但在资源有限的情况下,其影响和疗效还有待分析。研究方法研究对象为2019-2021年期间在秘鲁利马国立肿瘤研究所(INEN)确诊为HER2阳性BC的18岁及以上女性患者,她们至少接受过一次皮下注射曲妥珠单抗的治疗。我们审查了医疗记录,以登记治疗特征、不良事件(AE)、疾病进展和生存状况。我们考虑了36个月和45个月的中位随访时间,以了解病情进展和生存状况。结果大多数患者年龄在 50 岁以上(54.29%)。肿瘤大小平均为 19.7 ± 16.1 毫米。44.78%的患者存在淋巴结。大多数患者接受辅助化疗(63.8%)作为一线治疗。对治疗结果的描述性分析显示,毒性发生率为30%,主要是关节痛(47.62%),其次是腹泻、疲劳和注射部位反应,与更大规模的研究相比,停药率相对较低。在出现 AEs 方面,人口统计学、临床和治疗特征的差异无统计学意义(P > 0.05)。在中位随访 36 个月和 45 个月期间,9 名患者的病情出现进展,总生存率(OS)分别为 98.6% 和 92.8%。结论研究表明,皮下注射曲妥珠单抗的有效性和安全性与静脉注射相当。针对特定地区的研究可为了解影响秘鲁或其他国家治疗效果的人口因素提供有价值的见解。此外,皮下注射曲妥珠单抗是一种更容易获得的替代疗法,有可能提高患者的依从性并优化医疗资源物流。
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引用次数: 0
Application of Intraoperative Radiotherapy in Early-Stage Breast Cancer Patients in a Clinical Setting. 术中放疗在早期乳腺癌患者中的临床应用。
IF 1.6 Q4 ONCOLOGY Pub Date : 2024-06-18 eCollection Date: 2024-01-01 DOI: 10.1155/2024/5551907
Ao Wang, Elchanan Quint, Ivan Kukeev, Ravit Agassi, Olga Belochitski, Gay Barski, Julie Vaynshtein

Background: Intraoperative radiation therapy (IORT) has gained popularity in recent years as an alternative to external beam whole breast radiation therapy (WBRT) for early-stage breast cancer. Here, we report 43-month recurrence and survival outcomes in a multiethnic cohort treated with IORT in a clinical context. Method: Two hundred and eleven patients with low-risk features were treated with IORT for early-stage breast cancer from 2014 to 2021. Selection criteria were based on Group Europeen de Curietherapie-European Society for Therapeutic Radiology and Oncology (GEC-ESTRO) guidelines: preferably unifocal intraductal carcinoma (IDC), aged > 50, tumor size ≤ 2.0 cm, and without lymph node involvement. All patients received 20 Gy of radiation dose during the lumpectomy. Information on patient and tumor characteristics was collected. Results: The mean age of this cohort was 67.5 years; 95.2% of patients are Jewish, and the rest are Bedouins (4.7%). Most tumors were intraductal carcinoma (97.2%) and stage 1 (94.8%). The mean follow-up time was 43.4 months. Bedouins had larger tumor sizes (mean 1.21 vs. 1.13 cm) and were younger at diagnosis than Jewish patients (mean 65.4 vs. 67.6 years), although the differences are not significant. The overall recurrence rate was 1.4%. One case of local recurrence (0.5%) and two cases of metastasis (0.9%) were observed during the study period. One patient died from metastasis. Conclusion: Our findings suggest that IORT in selected low-risk patients can achieve an excellent prognosis with low rates of recurrence and metastasis.

背景:术中放疗(IORT)作为早期乳腺癌外照射全乳腺放疗(WBRT)的替代疗法,近年来越来越受欢迎。在此,我们报告了一个多种族队列接受 IORT 治疗 43 个月后的复发和生存情况。治疗方法2014年至2021年,211名具有低风险特征的早期乳腺癌患者接受了IORT治疗。选择标准基于欧洲放射治疗和肿瘤学会(GEC-ESTRO)指南:最好是单灶导管内癌(IDC),年龄大于 50 岁,肿瘤大小小于 2.0 厘米,无淋巴结受累。所有患者在肿瘤切除术中都接受了 20 Gy 的放射剂量。收集了患者和肿瘤特征的相关信息。研究结果患者平均年龄为 67.5 岁;95.2% 的患者为犹太人,其余为贝都因人(4.7%)。大多数肿瘤为导管内癌(97.2%)和一期(94.8%)。平均随访时间为 43.4 个月。贝都因人的肿瘤尺寸较大(平均 1.21 厘米对 1.13 厘米),确诊时的年龄也比犹太患者年轻(平均 65.4 岁对 67.6 岁),但差异并不显著。总复发率为 1.4%。研究期间观察到一例局部复发(0.5%)和两例转移(0.9%)。一名患者死于转移。结论:我们的研究结果表明,对选定的低风险患者进行 IORT 治疗可获得良好的预后,且复发率和转移率较低。
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引用次数: 0
Insights Into the Emerging Entity of HER2-Low Breast Cancer. 洞察新出现的 HER2 低度乳腺癌实体。
IF 1.6 Q4 ONCOLOGY Pub Date : 2024-06-13 eCollection Date: 2024-01-01 DOI: 10.1155/2024/2853007
Georges El Haddad, Ernest Diab, Michel Hajjar, Maroun Aoun, Farid Mallat, Ziad Zalaquett, Hampig-Raphael Kourie

Human epidermal growth factor receptor 2 (HER2)-low breast cancer (BC) is a subtype of BC that has been recently recognized as a separate clinical entity with distinct clinical and molecular characteristics. It is defined by a low level of HER2 protein expression, which distinguishes it from other more aggressive BC subtypes. Early studies suggest that it may have a more favorable prognosis than HER2-positive BC, as it is less likely to spread to other parts of the body and may be more responsive to standard BC treatments such as chemotherapy, radiation therapy, and hormone therapy. Given the relative new emergence of HER2-low BC, there is still much to be learned about this subtype; ongoing research is focused on identifying the underlying genetic mutations that contribute to HER2-low BC as well as developing targeted therapies that can improve outcomes for patients with this disease. This review is aimed at summarizing the current clinical knowledge on HER2-low BC, with the aim of creating a better understanding of this entity and paving the way for potential interventions and a new standard of care.

人表皮生长因子受体 2(HER2)低表达乳腺癌(BC)是最近被认为是一种独立临床实体的 BC 亚型,具有不同的临床和分子特征。它的定义是 HER2 蛋白表达水平低,这使其有别于其他更具侵袭性的 BC 亚型。早期研究表明,它的预后可能比 HER2 阳性 BC 更好,因为它较少扩散到身体的其他部位,对化疗、放疗和激素治疗等标准 BC 治疗的反应可能更强。鉴于 HER2 低度 BC 的出现相对较晚,人们对这一亚型仍有很多需要了解的地方;目前的研究重点是确定导致 HER2 低度 BC 的潜在基因突变,以及开发可改善该病患者预后的靶向疗法。本综述旨在总结目前有关 HER2 低水平 BC 的临床知识,目的是更好地了解这一实体,为潜在的干预措施和新的治疗标准铺平道路。
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引用次数: 0
Comprehensive Immunohistochemical Analysis of Epithelial-Mesenchymal Transition Biomarkers in the Invasive Micropapillary Cancer of the Breast. 乳腺浸润性微乳头状癌上皮-间质转化生物标志物的免疫组化综合分析
IF 1.6 Q4 ONCOLOGY Pub Date : 2024-06-11 eCollection Date: 2024-01-01 DOI: 10.1155/2024/2350073
Ozden Oz, Funda Alkan Tasli, Resmiye Irmak Yuzuguldu, Baha Zengel, Demet Kocatepe Cavdar, Merih Guray Durak, Raika Durusoy

Background: Invasive micropapillary carcinoma (IMPC) of the breast is commonly associated with a poor prognosis due to its high incidence of lymphovascular invasion and lymph node metastasis (LNM). Our study is aimed at investigating the prognostic significance of the expressions of E-cadherin (E-cad), N-cadherin (N-cad), CD44s, and β-catenin (β-cat). In addition, it is aimed at deciphering the consistency of these markers between the IMPC, the invasive breast carcinoma, no-special type (IBC-NST), and LNM components in the same IMPC cases. Methods: Sixty-two IMPC cases with LNM from 1996 to 2018 were analyzed. Immunohistochemical staining was performed separately on the three regions for each patient. Statistical analyses included Kaplan-Meier, Cox regression, and McNemar's statistical tests. Results: Loss of CD44 expression in IMPC, IBC-NST, and LNM areas was associated with poor prognosis in overall survival (OS) (p = 0.010, p < 0.0005, p = 0.025). Loss of CD44 expression in the IBC-NST, gain of N-cad expression in the IMPC, and loss of β-cat expression in the LNM areas were indicators of poor prognosis in disease-free survival (DFS) (p = 0.005, p = 0.041, p = 0.009). Conclusion: Our evaluation of this rare subtype, focusing on the expression of key epithelial-mesenchymal transition (EMT) molecules, revealed that it shares characteristics with the IBC-NST component within mixed tumors. Notably, contrary to expectations, a reduction in CD44 expression was found to adversely affect both OS and DFS. By conducting staining procedures simultaneously across three regions within the same patient, a novel approach has provided valuable insights into the mechanisms of EMT.

背景:乳腺浸润性微乳头状癌(IMPC)由于淋巴管侵犯和淋巴结转移(LNM)发生率高,通常预后较差。我们的研究旨在探讨 E-cad、N-cad、CD44s 和 β-catenin(β-cat)表达的预后意义。此外,该研究还旨在解读同一 IMPC 病例中 IMPC、浸润性乳腺癌、无特殊类型(IBC-NST)和 LNM 成分之间这些标记物的一致性。研究方法分析了1996年至2018年期间62例伴有LNM的IMPC病例。对每位患者的三个区域分别进行免疫组化染色。统计分析包括 Kaplan-Meier、Cox 回归和 McNemar 统计检验。结果CD44在IMPC、IBC-NST和LNM区域的表达缺失与总生存期(OS)的不良预后相关(p = 0.010,p < 0.0005,p = 0.025)。IBC-NST中CD44表达缺失、IMPC中N-cad表达增高、LNM区域中β-cat表达缺失是无病生存期(DFS)预后不良的指标(p = 0.005、p = 0.041、p = 0.009)。结论我们对这一罕见亚型进行了评估,重点研究了关键上皮-间质转化(EMT)分子的表达,结果发现它与混合瘤中的IBC-NST成分具有相同的特征。值得注意的是,与预期相反,CD44表达的减少会对OS和DFS产生不利影响。通过对同一患者的三个区域同时进行染色,一种新方法为了解 EMT 的机制提供了宝贵的见解。
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引用次数: 0
BRAF Expression and Copy Number Alterations Predict Unfavorable Tumor Features and Adverse Outcomes in Patients With Breast Cancer. BRAF 表达和拷贝数改变可预测乳腺癌患者的不利肿瘤特征和不良预后。
IF 1.6 Q4 ONCOLOGY Pub Date : 2024-05-30 eCollection Date: 2024-01-01 DOI: 10.1155/2024/6373900
Yazan R Alhamdan, Nehad M Ayoub, Sara K Jaradat, Aymen Shatnawi, Rami J Yaghan

Background: The role of BRAF in breast cancer pathogenesis is still unclear. To address this knowledge gap, this study is aimed at evaluating the impact of BRAF gene expression and copy number alterations (CNAs) on clinicopathologic characteristics and survival in patients with breast cancer. Methods: The Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) dataset was obtained from the cBioPortal public domain. Tumoral BRAF mRNA expression and CNAs along with demographic and tumor data for patients with breast cancer were retrieved. The association of BRAF expression and CNAs with breast cancer clinicopathologic characteristics was analyzed. The impact of BRAF mRNA expression on the overall survival of patients was assessed using Kaplan-Meier survival analysis. Results: BRAF gene mRNA log intensity expression was positively correlated with tumor size and the Nottingham Prognostic Index (NPI) (p < 0.001). Alternatively, BRAF gene expression was negatively correlated with the age at diagnosis (p = 0.003). The average BRAF mRNA expression was significantly higher in premenopausal patients, patients with high tumor grade, hormone receptor-negative status, and non-luminal tumors compared to postmenopausal patients, patients with low-grade, hormone receptor-positive, and luminal disease. BRAF gain and high-level amplification copy numbers were significantly associated with higher NPI scores and larger tumor sizes compared to neutral copy number status. Survival analysis revealed no discernible differences in overall survival for patients with low and high BRAF mRNA expression. Conclusion: High BRAF mRNA expression as well as the gain and high-level amplification copy numbers were associated with advanced tumor characteristics and unfavorable prognostic factors in breast cancer. BRAF could be an appealing target for the treatment of premenopausal patients with hormone receptor-negative breast cancer.

背景:BRAF 在乳腺癌发病机制中的作用尚不清楚。为了填补这一知识空白,本研究旨在评估 BRAF 基因表达和拷贝数改变(CNA)对乳腺癌患者临床病理特征和生存期的影响。研究方法从 cBioPortal 公共域获取国际乳腺癌分子分类联盟(METABRIC)数据集。检索了乳腺癌患者的肿瘤 BRAF mRNA 表达和 CNAs 以及人口统计学和肿瘤数据。分析了 BRAF 表达和 CNAs 与乳腺癌临床病理特征的关系。使用 Kaplan-Meier 生存分析评估了 BRAF mRNA 表达对患者总生存期的影响。结果BRAF基因mRNA对数强度表达与肿瘤大小和诺丁汉预后指数(NPI)呈正相关(p < 0.001)。另外,BRAF 基因表达与诊断年龄呈负相关(p = 0.003)。绝经前患者、肿瘤分级高、激素受体阴性和非腔隙性肿瘤患者的 BRAF mRNA 平均表达量明显高于绝经后患者、肿瘤分级低、激素受体阳性和腔隙性疾病患者。与中性拷贝数状态相比,BRAF增益和高水平扩增拷贝数与较高的NPI评分和较大的肿瘤体积有显著相关性。生存分析显示,BRAF mRNA表达量低和高的患者在总生存率上没有明显差异。结论BRAF mRNA的高表达以及增益和高水平扩增拷贝数与乳腺癌的晚期肿瘤特征和不利预后因素有关。BRAF可能是治疗绝经前激素受体阴性乳腺癌患者的一个有吸引力的靶点。
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引用次数: 0
Male Breast Cancer: An Updated Review of Patient Characteristics, Genetics, and Outcome. 男性乳腺癌:患者特征、遗传学和预后的最新回顾。
IF 1.9 Q4 ONCOLOGY Pub Date : 2024-03-23 eCollection Date: 2024-01-01 DOI: 10.1155/2024/9003572
Vidhu Shekhar Khare, Farhanul Huda, Subhasis Misra, Kanmatha Reddy Amulya, Nirmal Raj, Summi Karn, Somprakas Basu

Male breast cancer (MBC) is a rare entity, underrepresented in population studies and clinical trials, resulting in management of MBC to be informed by current research on female breast cancer (FBC). A literature review was conducted by accessing relevant articles on 2 databases, by searching keywords "male breast cancer". A total of 29 articles from year 2011 to 2022 were selected for this review. The authors found that male breast cancer generally occurs later in life with higher stage, higher grade, and more estrogen receptor (ER) positive tumours. Most of the studies noted the mean age for MBCs at the time of presentation as >60 years. Risk factors for male breast cancer include family history, obesity, lower physical activity, and syndromes like the Klinefelter syndrome. Positive family history is much higher in MBC compared to FBC (30.9 vs. 18.4%). BRCA 2 cancers constitute a higher proportion compared to FBCs. A lot of genetic mutations have been observed. Some show promise to assess disease-specific survival and proliferative rate like TWIST1 and RUNX3, among others. MBCs usually present with a palpable lump in central region, with a bigger size and chance of nodal involvement and metastasis compared to FBCs. They are mostly infiltrating ductal type and hormone receptor positive, with worse histological grade. Treatment usually follows the same principles as FBCs (systemic therapy, surgical excision, and radiotherapy), with poorer prognosis to same treatment approach, possibly owing to its advanced stage at presentation. This is a rare entity which requires further research to ascertain need for different management approach than FBCs.

男性乳腺癌(MBC)是一种罕见的癌症,在人群研究和临床试验中的代表性不足,因此男性乳腺癌的治疗需要参考目前对女性乳腺癌(FBC)的研究。我们在两个数据库中以 "男性乳腺癌 "为关键词搜索相关文章,进行了文献综述。本次综述共选取了 2011 年至 2022 年的 29 篇文章。作者发现,男性乳腺癌一般发生在晚期,分期较晚,级别较高,雌激素受体(ER)阳性肿瘤较多。大多数研究指出,男性乳腺癌患者发病时的平均年龄大于 60 岁。男性乳腺癌的风险因素包括家族史、肥胖、运动量较少以及克氏综合征等综合征。与女性乳腺癌相比,阳性家族史在男性乳腺癌中的比例要高得多(30.9% 对 18.4%)。与前列腺癌患者相比,BRCA 2 癌症所占比例更高。已观察到许多基因突变。有些基因突变有望评估疾病特异性生存率和增殖率,如 TWIST1 和 RUNX3 等。多发性乳腺癌通常表现为中央区域可触及的肿块,与前列腺癌相比,其体积更大,结节受累和转移的几率也更大。它们大多为浸润性导管型,激素受体阳性,组织学分级较低。治疗原则通常与前列腺癌相同(全身治疗、手术切除和放射治疗),可能由于发病时已属晚期,采用相同治疗方法的预后较差。这是一种罕见病,需要进一步研究,以确定是否需要采取与前列腺癌不同的治疗方法。
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引用次数: 0
Evaluation of Features in Probably Benign and Malignant Nonmass Enhancement in Breast MRI. 评估乳腺 MRI 中可能存在的良性和恶性非肿块增强的特征。
IF 1.9 Q4 ONCOLOGY Pub Date : 2024-03-15 eCollection Date: 2024-01-01 DOI: 10.1155/2024/6661849
Nasrin Ahmadinejad, Fahimeh Azizinik, Pershang Khosravi, Ala Torabi, Amirhassan Mohajeri, Arvin Arian

Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) is a highly sensitive breast imaging modality in detecting breast carcinoma. Nonmass enhancement (NME) is uniquely seen on MRI of the breast. The correlation between NME features and pathologic results has not been extensively explored. Our goal was to evaluate the characteristics of probably benign and suspicious NME lesions in MRI and determine which features are more associated with malignancy. We performed a retrospective research after approval by the hospital ethics committee on women who underwent breast MRI from March 2017 to March 2020 and identified 63 lesions of all 400 NME that were categorized as probably benign or suspicious according to the BI-RADS classification (version 2013). MRI features of NME findings including the location, size, distribution and enhancement pattern, kinetic curve, diffusion restriction, and also pathology result or 6-12-month follow-up MRI were evaluated and analyzed in each group (probably benign or suspicious NME). Vacuum-guided biopsies (VAB) were performed under mammographic or sonographic guidance and confirmed with MRI by visualization of the inserted clips. Segmental distribution and clustered ring internal enhancement were significantly associated with malignancy (p value<0.05), while linear distribution or homogeneous enhancement patterns were associated with benignity (p value <0.05). Additionally, the plateau and washout types in the dynamic curve were only seen in malignant lesions (p value <0.05). The presence of DWI restriction in NME lesions was also found to be a statistically important factor. Understanding the imaging findings of malignant NME is helpful to determine when biopsy is indicated. The correlation between NME features and pathologic results is critical in making appropriate management.

动态对比增强磁共振成像(DCE-MRI)是一种高灵敏度的乳腺成像模式,可用于检测乳腺癌。非肿块增强(NME)是乳腺磁共振成像的独特表现。NME 特征与病理结果之间的相关性尚未得到广泛探讨。我们的目标是评估核磁共振成像中可能是良性和可疑的 NME 病变的特征,并确定哪些特征与恶性肿瘤更相关。经医院伦理委员会批准后,我们对 2017 年 3 月至 2020 年 3 月期间接受乳腺 MRI 检查的女性进行了回顾性研究,在所有 400 个 NME 病灶中确定了 63 个病灶,并根据 BI-RADS 分类(2013 版)将其归类为可能良性或可疑病灶。对每组(可能是良性或可疑的 NME)NME 发现的 MRI 特征进行了评估和分析,包括位置、大小、分布和增强模式、动力学曲线、弥散受限以及病理结果或 6-12 个月的随访 MRI。真空引导活检(VAB)是在乳腺X光或超声引导下进行的,并通过核磁共振成像确认插入的夹子。节段性分布和簇状环形内部强化与恶性程度显著相关(P值P值
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引用次数: 0
Assessment of miRNA-10b Expression Levels as a Potential Precursor to Metastasis in Localized and Locally Advanced/Metastatic Breast Cancer among Iraqi Patients. 评估 miRNA-10b 表达水平作为伊拉克患者局部和局部晚期/转移性乳腺癌转移的潜在前兆。
IF 1.9 Q4 ONCOLOGY Pub Date : 2024-02-28 eCollection Date: 2024-01-01 DOI: 10.1155/2024/2408355
Mays Abdallah, Ismail H Aziz, Ahmed Zuhair Alsammarraie

Breast cancer (BC) stands as the most prevalent form of carcinoma among women, ranking as the second leading cause of cancer-related mortality in the female population. The objective of this study is to assess the expression of miR-10b and determine its diagnostic and prognostic significance in breast cancer patients across various disease stages. The investigation was carried out in Baghdad at the Oncology Teaching Hospital within Baghdad Medical City and the Oncology Unit at Al-Yarmouk Teaching Hospital. A total of 150 samples were included and divided into two groups: the blood group consisting of 90 samples (including control subjects, localized BC patients, and those with metastatic and locally advanced BC) and the tissue group comprising 60 samples (representing both benign and malignant BC cases). The study spanned from March 2022 to January 2023, with patients' ages ranging from 24 to 75 years. The primary focus of this investigation was to identify the gene expression of miRNA-10b in all sample types. This was achieved by measuring gene expression levels and normalizing them to the level of a housekeeping gene (U6), and quantification was carried out considering the ΔCt value and the fold change method (2-ΔΔCt). The results revealed an upregulated fold expression of miRNA-10b, particularly in locally advanced and metastatic BC, where the expression was significantly higher compared to the other groups, with a fold expression of 1.770 ± 0.1070. In localized breast cancer, the fold expression was 1.624 ± 0.064, and in malignant tissue, it measured 1.546 ± 0.06754, all relative to apparently healthy control subjects. In summary, our research provides compelling evidence supporting the classification of miRNA-10b as an oncogenic factor in BC. The central involvement of miRNA-10b in the tumorigenic processes of BC highlights its reference for developing novel targeted therapeutic interventions and detection biomarkers for BC treatment. Notably, elevated expression of miRNA-10b was observed in BC tissues, correlating with an unfavorable distant metastasis-free survival outcome.

乳腺癌(BC)是女性中最常见的一种癌症,也是女性癌症相关死亡的第二大原因。本研究的目的是评估 miR-10b 的表达,并确定其在不同疾病阶段的乳腺癌患者中的诊断和预后意义。调查在巴格达医疗城的肿瘤教学医院和 Al-Yarmouk 教学医院的肿瘤科进行。共纳入了 150 份样本,并将其分为两组:由 90 份样本组成的血液组(包括对照组、局部乳腺癌患者、转移性和局部晚期乳腺癌患者)和由 60 份样本组成的组织组(包括良性和恶性乳腺癌病例)。研究时间跨度为 2022 年 3 月至 2023 年 1 月,患者年龄从 24 岁到 75 岁不等。这项研究的主要重点是确定 miRNA-10b 在所有样本类型中的基因表达。为此,研究人员测量了基因表达水平,并将其与看家基因(U6)的水平进行归一化,然后采用ΔCt 值和折叠变化法(2-ΔΔCt)进行量化。结果表明,miRNA-10b的折叠表达量上调,尤其是在局部晚期和转移性乳腺癌中,其表达量明显高于其他组别,折叠表达量为1.770 ± 0.1070。在局部乳腺癌中,折合表达量为 1.624 ± 0.064,在恶性组织中,折合表达量为 1.546 ± 0.06754,所有这些都是相对于表面健康的对照组而言的。总之,我们的研究提供了令人信服的证据,支持将 miRNA-10b 归类为 BC 的致癌因子。miRNA-10b 在 BC 肿瘤发生过程中的核心参与作用凸显了它在开发新的靶向治疗干预措施和检测 BC 治疗生物标志物方面的参考价值。值得注意的是,在BC组织中观察到miRNA-10b的表达升高,这与不利的无远处转移生存结果相关。
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引用次数: 0
A Pilot Study of the Combination of Entinostat with Capecitabine in Advanced Breast Cancer. 恩替诺特与卡培他滨联合治疗晚期乳腺癌的试点研究
IF 1.6 Q4 ONCOLOGY Pub Date : 2024-02-07 eCollection Date: 2024-01-01 DOI: 10.1155/2024/5515966
Trish Millard, Christiana Brenin, Clare Humphrey, Ajay Dhakal, Carla Falkson, Gina Petroni, Nolan A Wages, Patrick Dillon

Background: Breast cancer has an unacceptably high recurrence rate when any residual disease is found following neoadjuvant treatment of high-risk disease. Based on clinical data suggesting an adjuvant role for epigenetic modifying agents in breast cancer and preclinical data suggesting synergistic activity of entinostat combined with capecitabine, we conducted a phase I, open-label study of these agents in metastatic breast cancer (MBC). Both agents have published doses for use in combination therapy, but the agents had not previously been combined with each other in a human trial.

Methods: A multisite phase I dose escalation study was performed at two academic centers. Patients with pretreated, HER2-negative MBC, and measurable disease were enrolled. Dual dose escalation was performed via a Bayesian partial order continual assessment method. Dose levels ranged from entinostat 3 mg to 5 mg and capecitabine 800 mg/m2 to 1000 mg/m2.

Results: Thirteen patients with MBC and a median of 4 lines of prior therapy were enrolled across four dose level combinations. The most common toxicities were neutropenia, thrombocytopenia, and palmar-plantar dysesthesia, which were expected toxicities. No new safety signals were observed. One dose-limiting toxicity was observed, which did not exceed a prespecified toxicity rate of 25%. The median treatment duration was 2.37 months. No partial nor complete responses were observed. The study was halted early prior to entering an expansion phase, due to drug supply limitations.

Conclusion: The tested dosing combinations of entinostat and capecitabine are likely safe in heavily pretreated metastatic breast cancer. This study's clinical investigation of entinostat in breast cancer was halted, but drug development of this agent continues outside the US. There remains a need for postoperative adjuvant drug therapy for the subpopulation of breast cancer patients with high-risk residual cancer after curative therapy. This trial is registered with NCT03473639.

背景:乳腺癌在对高危疾病进行新辅助治疗后,如果发现任何残留疾病,其复发率都高得令人无法接受。临床数据表明表观遗传修饰药物对乳腺癌有辅助治疗作用,而临床前数据表明恩替诺司他与卡培他滨联用有协同作用,基于这些数据,我们对这些药物在转移性乳腺癌(MBC)中的应用进行了一项开放标签 I 期研究。这两种药物都已公布了用于联合治疗的剂量,但此前还未在人体试验中进行过联合应用:方法:两个学术中心开展了一项多点 I 期剂量递增研究。方法:在两个学术中心开展了一项多点 I 期剂量递增研究,入组患者均为接受过预处理、HER2 阴性 MBC 且病情可测量的患者。通过贝叶斯偏序持续评估法进行双剂量递增。剂量水平从恩替诺特 3 毫克到 5 毫克不等,卡培他滨 800 毫克/平方米到 1000 毫克/平方米不等:13名中性粒细胞白血病患者接受了四种剂量组合的治疗,中位数为4种既往疗法。最常见的毒性反应是中性粒细胞减少、血小板减少和掌跖感觉障碍,这些都是预料之中的毒性反应。没有观察到新的安全性信号。观察到一种剂量限制性毒性,但未超过 25% 的预设毒性率。中位治疗时间为 2.37 个月。未观察到部分或完全应答。由于药物供应限制,研究在进入扩展阶段之前提前结束:结论:恩替诺司他和卡培他滨的试验剂量组合对于重度预处理转移性乳腺癌可能是安全的。这项研究对恩替诺特治疗乳腺癌的临床研究已经停止,但这种药物在美国以外的药物开发仍在继续。对于根治性治疗后有高危残留癌的乳腺癌患者,仍然需要术后辅助药物治疗。该试验已在 NCT03473639 上注册。
{"title":"A Pilot Study of the Combination of Entinostat with Capecitabine in Advanced Breast Cancer.","authors":"Trish Millard, Christiana Brenin, Clare Humphrey, Ajay Dhakal, Carla Falkson, Gina Petroni, Nolan A Wages, Patrick Dillon","doi":"10.1155/2024/5515966","DOIUrl":"10.1155/2024/5515966","url":null,"abstract":"<p><strong>Background: </strong>Breast cancer has an unacceptably high recurrence rate when any residual disease is found following neoadjuvant treatment of high-risk disease. Based on clinical data suggesting an adjuvant role for epigenetic modifying agents in breast cancer and preclinical data suggesting synergistic activity of entinostat combined with capecitabine, we conducted a phase I, open-label study of these agents in metastatic breast cancer (MBC). Both agents have published doses for use in combination therapy, but the agents had not previously been combined with each other in a human trial.</p><p><strong>Methods: </strong>A multisite phase I dose escalation study was performed at two academic centers. Patients with pretreated, HER2-negative MBC, and measurable disease were enrolled. Dual dose escalation was performed via a Bayesian partial order continual assessment method. Dose levels ranged from entinostat 3 mg to 5 mg and capecitabine 800 mg/m<sup>2</sup> to 1000 mg/m<sup>2</sup>.</p><p><strong>Results: </strong>Thirteen patients with MBC and a median of 4 lines of prior therapy were enrolled across four dose level combinations. The most common toxicities were neutropenia, thrombocytopenia, and palmar-plantar dysesthesia, which were expected toxicities. No new safety signals were observed. One dose-limiting toxicity was observed, which did not exceed a prespecified toxicity rate of 25%. The median treatment duration was 2.37 months. No partial nor complete responses were observed. The study was halted early prior to entering an expansion phase, due to drug supply limitations.</p><p><strong>Conclusion: </strong>The tested dosing combinations of entinostat and capecitabine are likely safe in heavily pretreated metastatic breast cancer. This study's clinical investigation of entinostat in breast cancer was halted, but drug development of this agent continues outside the US. There remains a need for postoperative adjuvant drug therapy for the subpopulation of breast cancer patients with high-risk residual cancer after curative therapy. This trial is registered with NCT03473639.</p>","PeriodicalId":46159,"journal":{"name":"International Journal of Breast Cancer","volume":"2024 ","pages":"5515966"},"PeriodicalIF":1.6,"publicationDate":"2024-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10866629/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139736340","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Strategies to Promote Empowerment Status of Breast Cancer Women. 促进乳腺癌妇女赋权地位的战略。
IF 1.9 Q4 ONCOLOGY Pub Date : 2024-02-05 eCollection Date: 2024-01-01 DOI: 10.1155/2024/3305399
Mohammad Amin Bahrami, Shahrzad Tabari, Sedigheh Tahmasebi, Vahid Zangouri, Ramin Ravangard

Background: As the second leading cause of death in women in the world, breast cancer has several physical and psychological effects. Nowadays, nonclinical approaches such as patient empowerment have been considered by physicians along with clinical care. Given the increasing number of breast cancer women worldwide, promoting the empowerment of these patients is one of the key factors affecting their survival and quality of life. Therefore, because of no comprehensive research on the empowerment needs and related improvement strategies, this study is aimed at determining the empowerment status of breast cancer patients referred to the Shahid Motahari Breast Cancer Clinic in Iran, Shiraz, and at providing strategies to improve their empowerment in 2021.

Methods: This applied study was conducted in two phases. In the quantitative phase, 310 Cancer-Related Patient Empowerment Scale questionnaires (Persian format) were distributed among the studied patients selected through the random sampling method in the clinic, and the items with "unacceptable status" became the basis for determining the empowerment strategies through the scoping review and semistructured interviews with 22 medical staff and patients through the thematic analysis. The collected data were analyzed using the SPSS 20.0 and MAXQDA10 software.

Results: The mean score of the participants' empowerment strategies was 3.58. The results showed that trust in the physician, family support, and spiritual beliefs could affect the empowerment of the studied patients. Moreover, the participants needed empowerment strategies in 11 scale items with unacceptable status, for which 46 strategies were determined in the scoping review and interview phase.

Conclusion: The results of this study provided useful strategies for empowering breast cancer patients, the most important of which were classified into five categories of financial support, informational support, interaction with the physician, occupational support, and complementary therapies, the use of which by the stakeholders could help to improve the patients' quality of life while improving their empowerment.

背景:乳腺癌是全球女性的第二大死因,它对女性的生理和心理都会造成影响。如今,医生在提供临床治疗的同时,也考虑采用非临床方法,如增强患者能力。鉴于全球乳腺癌妇女人数不断增加,促进这些患者的赋权是影响其生存和生活质量的关键因素之一。因此,由于没有关于赋权需求和相关改进策略的全面研究,本研究旨在确定转诊至伊朗设拉子市 Shahid Motahari 乳腺癌诊所的乳腺癌患者的赋权状况,并提供在 2021 年提高其赋权的策略:这项应用研究分两个阶段进行。在定量研究阶段,通过随机抽样方法在诊所中挑选出的患者中发放了 310 份《癌症相关患者赋权量表》(波斯语格式)问卷,并通过范围审查和对 22 名医务人员和患者进行的半结构式访谈(主题分析),将 "不可接受的状况 "项目作为确定赋权策略的基础。收集到的数据使用 SPSS 20.0 和 MAXQDA10 软件进行分析:参与者赋权策略的平均得分为 3.58 分。结果表明,对医生的信任、家庭支持和精神信仰会影响所研究患者的赋权。此外,在 11 个不可接受的量表项目中,参与者需要赋权策略,在范围审查和访谈阶段确定了 46 种策略:本研究的结果为增强乳腺癌患者的能力提供了有用的策略,其中最重要的策略分为经济支持、信息支持、与医生互动、职业支持和辅助疗法五类,利益相关者使用这些策略有助于提高患者的生活质量,同时增强他们的能力。
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引用次数: 0
期刊
International Journal of Breast Cancer
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