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The Effects of Anlotinib Combined with Chemotherapy following Progression on Cyclin-Dependent Kinase 4/6 Inhibitor in Hormone Receptor-Positive Metastatic Breast Cancer 安罗替尼联合化疗对激素受体阳性转移性乳腺癌进展期细胞周期蛋白依赖性激酶 4/6 抑制剂的影响
IF 1.9 4区 医学 Q3 OBSTETRICS & GYNECOLOGY Pub Date : 2024-08-02 DOI: 10.1155/2024/5396107
Ting Xu, Weili Xiong, Lili Zhang, Yuan Yuan

Purpose. Endocrine therapy combined with cyclin-dependent kinase (CDK) 4/6 inhibitors (CDK4/6i) is the preferred treatment for hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2–) metastatic breast cancer (MBC). However, there are currently no recommendations for therapeutic strategies after progression on CDK4/6i-based treatment. This study aimed to examine the efficacy and safety of anlotinib plus chemotherapy in HR+/HER2– MBC after progression on CDK4/6 inhibitors. Methods. We collected data from 32 patients with HR+/HER2– MBC treated with anlotinib plus chemotherapy after progressing on CDK4/6i at Jiangsu Cancer Hospital from March 2020 to October 2023. The median follow-up was 9.1 months (range, 2.0–19.7 months) as of the data cutoff date in October 2023. The primary endpoint was median progression-free survival (PFS); secondary endpoints included objective response rate (ORR), disease control rate (DCR), and adverse events. Results. The median PFS (mPFS) of all patients was 7.6 months (95% confidence interval (CI), 5.75–9.45). There was no significant difference in mPFS between patients who responded to prior CDK4/6i treatment and those who did not (8.3 months vs. 6.8 months, p = 0.580). Besides, the ORR was 34.4% and DCR was 93.8%. The most frequently observed adverse events were anemia (50.0%), neutropenia (40.6%), thrombocytopenia (34.4%), and epistaxis (34.4%). Dose interruption or reductions due to adverse events occurred in 2 (6.3%) and 5 (15.6%) patients, respectively. Conclusions. The study preliminarily demonstrates that anlotinib combined with chemotherapy may be an optional recommendation for patients with HR+/HER2– metastatic breast cancer who have progressed after CDK4/6i.

目的。内分泌治疗联合细胞周期蛋白依赖性激酶(CDK)4/6抑制剂(CDK4/6i)是激素受体阳性(HR+)/人表皮生长因子受体2阴性(HER2-)转移性乳腺癌(MBC)的首选治疗方法。然而,目前还没有关于CDK4/6i治疗进展后治疗策略的建议。本研究旨在探讨安罗替尼联合化疗对CDK4/6抑制剂治疗进展后的HR+/HER2- MBC的疗效和安全性。研究方法我们收集了2020年3月至2023年10月期间江苏省肿瘤医院收治的32例CDK4/6i治疗进展后接受安罗替尼联合化疗的HR+/HER2- MBC患者的数据。截至2023年10月数据截止日,中位随访时间为9.1个月(2.0-19.7个月)。主要终点为中位无进展生存期(PFS);次要终点包括客观反应率(ORR)、疾病控制率(DCR)和不良事件。研究结果所有患者的中位无进展生存期(mPFS)为7.6个月(95% 置信区间(CI),5.75-9.45)。既往接受过CDK4/6i治疗的患者与未接受过CDK4/6i治疗的患者的中位生存期无明显差异(8.3个月 vs. 6.8个月,P = 0.580)。此外,ORR为34.4%,DCR为93.8%。最常见的不良反应是贫血(50.0%)、中性粒细胞减少(40.6%)、血小板减少(34.4%)和鼻衄(34.4%)。分别有 2 例(6.3%)和 5 例(15.6%)患者因不良反应而中断或减少剂量。结论该研究初步证明,对于CDK4/6i治疗后病情进展的HR+/HER2-转移性乳腺癌患者,可选择推荐安罗替尼联合化疗。
{"title":"The Effects of Anlotinib Combined with Chemotherapy following Progression on Cyclin-Dependent Kinase 4/6 Inhibitor in Hormone Receptor-Positive Metastatic Breast Cancer","authors":"Ting Xu,&nbsp;Weili Xiong,&nbsp;Lili Zhang,&nbsp;Yuan Yuan","doi":"10.1155/2024/5396107","DOIUrl":"https://doi.org/10.1155/2024/5396107","url":null,"abstract":"<div>\u0000 <p><i>Purpose</i>. Endocrine therapy combined with cyclin-dependent kinase (CDK) 4/6 inhibitors (CDK4/6i) is the preferred treatment for hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2–) metastatic breast cancer (MBC). However, there are currently no recommendations for therapeutic strategies after progression on CDK4/6i-based treatment. This study aimed to examine the efficacy and safety of anlotinib plus chemotherapy in HR+/HER2– MBC after progression on CDK4/6 inhibitors. <i>Methods</i>. We collected data from 32 patients with HR+/HER2– MBC treated with anlotinib plus chemotherapy after progressing on CDK4/6i at Jiangsu Cancer Hospital from March 2020 to October 2023. The median follow-up was 9.1 months (range, 2.0–19.7 months) as of the data cutoff date in October 2023. The primary endpoint was median progression-free survival (PFS); secondary endpoints included objective response rate (ORR), disease control rate (DCR), and adverse events. <i>Results</i>. The median PFS (mPFS) of all patients was 7.6 months (95% confidence interval (CI), 5.75–9.45). There was no significant difference in mPFS between patients who responded to prior CDK4/6i treatment and those who did not (8.3 months vs. 6.8 months, <i>p</i> = 0.580). Besides, the ORR was 34.4% and DCR was 93.8%. The most frequently observed adverse events were anemia (50.0%), neutropenia (40.6%), thrombocytopenia (34.4%), and epistaxis (34.4%). Dose interruption or reductions due to adverse events occurred in 2 (6.3%) and 5 (15.6%) patients, respectively. <i>Conclusions</i>. The study preliminarily demonstrates that anlotinib combined with chemotherapy may be an optional recommendation for patients with HR+/HER2– metastatic breast cancer who have progressed after CDK4/6i.</p>\u0000 </div>","PeriodicalId":56326,"journal":{"name":"Breast Journal","volume":null,"pages":null},"PeriodicalIF":1.9,"publicationDate":"2024-08-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1155/2024/5396107","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141966559","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
Neoadjuvant Endocrine Therapy Compared to Neoadjuvant Chemotherapy in Node-Positive HR+, HER2− Breast Cancer (Nodal pCR and the Rate of ALND): A Systematic Review and Meta-Analysis 结节阳性 HR+、HER2- 乳腺癌新辅助内分泌治疗与新辅助化疗的比较(结节 pCR 和 ALND 率):系统回顾与元分析
IF 1.9 4区 医学 Q3 OBSTETRICS & GYNECOLOGY Pub Date : 2024-08-01 DOI: 10.1155/2024/8866756
Mahtab Vasigh, Mohammadreza Karoobi, Austin D. Williams, Fasika Molla Abreha, Richard J. Bleicher, Seyed Mostafa Meshkati Yazd, Tahereh Shamsi, Ramesh Omranipour, Ahmad Elahi, David Farhat, Mehran Habibi

Introduction. Patients with hormone receptor-positive (HR+), HER2-negative (HER2−) breast cancers have the lowest response to neoadjuvant therapy of all subtypes. The role of neoadjuvant endocrine therapy (NET) in clinically node-positive (cN+), HR+, HER2− patients is evaluated in this meta-analysis. Methods. This study was performed between January 2010 and August 2022. We evaluated the node pathologic complete response (pCR) and axillary lymph node dissection (ALND) rates after neoadjuvant endocrine therapy (NET). Results. 18,037 HR+, HER2−, cN+ stage II and stage III breast cancer patients within eleven studies received neoadjuvant treatments. 3,707 (20.6%) patients received NET and 14,330 (79.4%) received NAC. The average age of the NET patients was higher than that of the neoadjuvant chemotherapy (NAC) patients (64.1 versus 47.6 years old, p < 0.001). 45.0% and 26.9% of the NET and the NAC groups underwent a lumpectomy. The pooled estimates of node pCR in NET and NAC groups were 8.9% and 14.9%, and the pooled proportion of ALND was 39.1% and 58.5%, respectively. Conclusion. The rate of node pCR was lower among cN+ patients who received NET compared to the NAC group. The rate of ALND among cN+ NET patients was lower than the NAC group, revealing more patients with residual nodal disease do not get ALND in the NET group. Further prospective studies are required to compare survival outcomes as a more reliable surrogate.

导言。在所有亚型中,激素受体阳性(HR+)、HER2-阴性(HER2-)乳腺癌患者对新辅助治疗的反应最低。本荟萃分析评估了新辅助内分泌治疗(NET)在临床结节阳性(cN+)、HR+、HER2-患者中的作用。研究方法本研究在2010年1月至2022年8月期间进行。我们评估了新辅助内分泌治疗(NET)后的结节病理完全反应率(pCR)和腋窝淋巴结清扫率(ALND)。结果如下11项研究中的18037名HR+、HER2-、cN+的II期和III期乳腺癌患者接受了新辅助治疗。3707名(20.6%)患者接受了NET治疗,14330名(79.4%)患者接受了NAC治疗。NET患者的平均年龄高于新辅助化疗(NAC)患者(64.1岁对47.6岁,P< 0.001)。45.0%的NET组和26.9%的NAC组患者接受了肿块切除术。NET组和NAC组结节pCR的汇总估计值分别为8.9%和14.9%,ALND的汇总比例分别为39.1%和58.5%。结论与NAC组相比,接受NET治疗的cN+患者的结节pCR率较低。cN+ NET患者的ALND率低于NAC组,这表明在NET组中有更多有残余结节病的患者没有获得ALND。需要进一步开展前瞻性研究,以比较生存结果作为更可靠的替代指标。
{"title":"Neoadjuvant Endocrine Therapy Compared to Neoadjuvant Chemotherapy in Node-Positive HR+, HER2− Breast Cancer (Nodal pCR and the Rate of ALND): A Systematic Review and Meta-Analysis","authors":"Mahtab Vasigh,&nbsp;Mohammadreza Karoobi,&nbsp;Austin D. Williams,&nbsp;Fasika Molla Abreha,&nbsp;Richard J. Bleicher,&nbsp;Seyed Mostafa Meshkati Yazd,&nbsp;Tahereh Shamsi,&nbsp;Ramesh Omranipour,&nbsp;Ahmad Elahi,&nbsp;David Farhat,&nbsp;Mehran Habibi","doi":"10.1155/2024/8866756","DOIUrl":"https://doi.org/10.1155/2024/8866756","url":null,"abstract":"<div>\u0000 <p><i>Introduction</i>. Patients with hormone receptor-positive (HR+), HER2-negative (HER2−) breast cancers have the lowest response to neoadjuvant therapy of all subtypes. The role of neoadjuvant endocrine therapy (NET) in clinically node-positive (cN+), HR+, HER2− patients is evaluated in this meta-analysis. <i>Methods</i>. This study was performed between January 2010 and August 2022. We evaluated the node pathologic complete response (pCR) and axillary lymph node dissection (ALND) rates after neoadjuvant endocrine therapy (NET). <i>Results</i>. 18,037 HR+, HER2−, cN+ stage II and stage III breast cancer patients within eleven studies received neoadjuvant treatments. 3,707 (20.6%) patients received NET and 14,330 (79.4%) received NAC. The average age of the NET patients was higher than that of the neoadjuvant chemotherapy (NAC) patients (64.1 versus 47.6 years old, <i>p</i> &lt; 0.001). 45.0% and 26.9% of the NET and the NAC groups underwent a lumpectomy. The pooled estimates of node pCR in NET and NAC groups were 8.9% and 14.9%, and the pooled proportion of ALND was 39.1% and 58.5%, respectively. <i>Conclusion</i>. The rate of node pCR was lower among cN+ patients who received NET compared to the NAC group. The rate of ALND among cN+ NET patients was lower than the NAC group, revealing more patients with residual nodal disease do not get ALND in the NET group. Further prospective studies are required to compare survival outcomes as a more reliable surrogate.</p>\u0000 </div>","PeriodicalId":56326,"journal":{"name":"Breast Journal","volume":null,"pages":null},"PeriodicalIF":1.9,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1155/2024/8866756","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141966749","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
Is the ≥1 cm Width of the Resection Margin in Benign and Borderline Phyllodes Tumor Necessary to Reduce Recurrence? 良性和边缘性鳞状上皮肿瘤的切除缘宽度≥1 厘米对减少复发有必要吗?
IF 1.9 4区 医学 Q3 OBSTETRICS & GYNECOLOGY Pub Date : 2024-08-01 DOI: 10.1155/2024/1432313
Nattakarn Changchit, Natthawadee Laokulrath, Pradit Rushatamukayanunt, Pongthep Pisarnturakit

Background. Phyllodes tumors (PTs) are fibroepithelial neoplasms of the breast, with current treatment guidelines recommending wide excision to achieve surgical margins of ≥1 cm to minimize the recurrence risk. However, diagnostic challenges with core biopsy specimens often result in suboptimal surgical margins. This study aims to elucidate the correlation between margin status and PT recurrence, thereby informing surgical decision-making and enhancing patient outcomes. Methods. This single-center, retrospective study reviewed records of Thai women diagnosed with PTs between 2011 and 2018, collecting data on demographics, clinical presentation, surgical approach, tumor grade, size, and margin status. The primary endpoint was recurrence. Results. Among 165 PT cases analyzed—49.1% borderline, 38.2% benign, and 12.7% malignant—the overall recurrence rate was 13.9% (n = 23) over a median follow-up of 4.5 years. No significant difference in recurrence rates was observed between patients with negative resection margins <1 cm (ranging from <1 mm to 9 mm) compared to those with ≥1 cm (10.2% vs. 7.1%, p = 1.00). Notably, in negative resection margins <1 cm group, a margin <1 mm (close margin) was associated with a significantly higher recurrence rate compared to margins of 1–9 mm (17.0% vs. 4.9%, p = 0.04). Borderline PTs followed the overall trend, while benign PTs showed increased recurrence with positive margins. Multivariate analysis indicated a significant association between margins <1 mm and recurrence (adjusted HR = 10.78 (95% CI 1.32–88.07), p = 0.027), highlighting an increased recurrence risk with more extensive positive margins. Conclusion. Our findings suggest that a wide surgical margin of ≥1 centimeter may not be necessary to prevent recurrence in benign and borderline PTs. Notably, surgical margins narrower than 1 millimeter substantially elevate the recurrence likelihood in cases of borderline PTs. Furthermore, the presence of positive surgical margins correlates with an increased recurrence rate in benign PTs. These findings highlight the critical need for a strategic approach in determining surgical margins, tailored specifically to the type of PT, to enhance patient outcomes effectively.

背景。鳞状上皮肿瘤(PTs)是乳腺纤维上皮肿瘤,目前的治疗指南建议广泛切除,使手术切缘≥1厘米,以最大限度地降低复发风险。然而,核心活检标本的诊断难题往往导致手术切缘不理想。本研究旨在阐明边缘状态与 PT 复发之间的相关性,从而为手术决策提供依据,提高患者的治疗效果。方法。这项单中心回顾性研究回顾了 2011 年至 2018 年间被诊断为 PT 的泰国女性的病历,收集了有关人口统计学、临床表现、手术方法、肿瘤分级、大小和边缘状态的数据。主要终点是复发。结果。在分析的165例PT病例中,49.1%为边缘性,38.2%为良性,12.7%为恶性,中位随访4.5年,总复发率为13.9%(n = 23)。切除边缘<1厘米(从<1毫米到9毫米不等)阴性的患者与切除边缘≥1厘米的患者相比,复发率无明显差异(10.2% vs. 7.1%,p = 1.00)。值得注意的是,在切除边缘<1厘米阴性组中,边缘<1毫米(近边缘)与1-9毫米边缘相比,复发率明显更高(17.0% vs. 4.9%,p = 0.04)。边缘PT的复发率与总体趋势一致,而良性PT的复发率则随着边缘阳性而增加。多变量分析表明,边缘<1 mm与复发之间存在显著关联(调整后HR = 10.78 (95% CI 1.32-88.07),p = 0.027),凸显出边缘阳性范围越广,复发风险越高。结论我们的研究结果表明,对于良性和边缘型 PT,≥1 厘米的宽手术切缘可能不是防止复发的必要条件。值得注意的是,手术切缘窄于 1 毫米会大大增加边缘型 PT 复发的可能性。此外,手术切缘呈阳性与良性 PT 复发率增加有关。这些研究结果突出表明,在确定手术切缘时亟需一种专门针对 PT 类型的战略性方法,以有效提高患者的治疗效果。
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引用次数: 0
Supraclavicular Irradiation Induces Lymphedema in Breast Cancer Patients Treated with Axillary Lymph Node Dissection and Taxane-Containing Chemotherapy 锁骨上照射会诱发接受腋窝淋巴结切除术和含紫杉类药物化疗的乳腺癌患者出现淋巴水肿
IF 1.9 4区 医学 Q3 OBSTETRICS & GYNECOLOGY Pub Date : 2024-07-31 DOI: 10.1155/2024/3250143
Nanae Horisawa, Akiyo Yoshimura, Isao Oze, Masataka Sawaki, Masaya Hattori, Haruru Kotani, Ayumi Kataoka, Yuri Ozaki, Kazuki Nozawa, Yuka Endo, Daiki Takatsuka, Ayaka Isogai, Hiroji Iwata

Purpose. Breast cancer-related lymphedema (LE) significantly impairs the patients’ quality of life. Axillary lymph node dissection (ALND) is a strong risk factor for LE in breast cancer surgery. In addition, postoperative administration of docetaxel (DTX) has been reported to be a risk factor for LE in patients who undergo ALND. Herein, we performed the risk of objective LE after ALND. Methods. Patients who visited the medical follow-up clinic between 12 November 2018 and 11 January 2019 and at least one year postoperatively were eligible for this study. The risk factors for objective LE according to taxane-containing regimen, radiation therapy, and body mass index and the effects of a taxane-containing regimen followed by supraclavicular irradiation on LE were examined. Results. A total of 214 patients were included in this analysis, and objective LE was observed in 52 patients (24%). Univariate and multivariate analyses showed that only supraclavicular field irradiation was a statistically significant risk factor for objective LE. In addition, the sequential use of taxane-containing regimens and supraclavicular RT was shown to be a more likely risk factor for LE than ALND alone. We also compared each taxane regimen with supraclavicular RT and found that DTX was more likely to be a risk factor for LE in cases of sequential use of supraclavicular RT than with ALND alone. However, when comparing DTX with supraclavicular RT and PTX with supraclavicular RT directly, there was no statistically significant difference in the risk of objective LE between the two groups. Conclusion. The risk for LE was more likely to be higher with the sequential use of taxane-containing chemotherapy and supraclavicular field irradiation. Therefore, management of LE is important in these cases.

目的:乳腺癌相关淋巴水肿(LE)严重影响患者的生活质量。乳腺癌相关淋巴水肿(LE)严重影响患者的生活质量。在乳腺癌手术中,腋窝淋巴结清扫术(ALND)是导致淋巴水肿的一个重要危险因素。此外,有报道称术后使用多西他赛(DTX)也是导致 ALND 患者淋巴水肿的风险因素之一。在此,我们对 ALND 后客观 LE 的风险进行了研究。方法。在 2018 年 11 月 12 日至 2019 年 1 月 11 日期间到医疗随访门诊就诊且术后至少一年的患者有资格参与本研究。根据含类固醇方案、放疗和体重指数,研究客观 LE 的风险因素,以及含类固醇方案后锁骨上照射对 LE 的影响。研究结果本次分析共纳入了 214 例患者,其中 52 例患者(24%)观察到了客观 LE。单变量和多变量分析表明,只有锁骨上野外照射是导致客观 LE 的具有统计学意义的危险因素。此外,连续使用含紫杉类药物的治疗方案和锁骨上 RT 比单独使用 ALND 更有可能成为 LE 的风险因素。我们还比较了每种含紫杉类药物方案与锁骨上 RT,发现在连续使用锁骨上 RT 的病例中,DTX 比单独使用 ALND 更有可能成为 LE 的风险因素。然而,如果将 DTX 与锁骨上 RT 和 PTX 与锁骨上 RT 直接进行比较,则两组患者发生客观 LE 的风险在统计学上没有显著差异。结论。相继使用含紫杉类药物的化疗和锁骨上野外照射时,发生 LE 的风险更高。因此,对这些病例进行 LE 管理非常重要。
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引用次数: 0
Health Information Needs of Breast Cancer Survivors: An Umbrella Review 乳腺癌幸存者的健康信息需求:综述
IF 1.9 4区 医学 Q3 OBSTETRICS & GYNECOLOGY Pub Date : 2024-07-15 DOI: 10.1155/2024/5889622
Nahid Gavili, Shahram Sedghi, Sirous Panahi, Maryam Razmgir

Purpose. The aim of this umbrella review was to identify the main information needs of breast cancer survivors. Since several reviews have already been done on this topic, conducting an umbrella review not only combines their results but also gives a comprehensive picture and informative summary of breast cancer survivors’ needs. Method. The search was performed in PubMed, Embase, Scopus, Web of Science, ProQuest, Cochrane, and Google Scholar from inception to the end of March 2024. This review was conducted according to the JBI methodology for umbrella reviews, and the report was based on Rutten’s category for information needs of patients with cancer. After removing duplicate and irrelevant articles, 14 systematic reviews were included in the analysis. The JBI checklist was used for evaluating the quality of eligible articles. Results. The information needs were classified into 11 main categories and 86 subcategories. As a result of this umbrella review, one category was added to Rutten’s 10 categories. Also, treatment information needs were introduced as the main identified category. Information on supportive care needs ranked second, and body image/sexuality information needs ranked third with a slight difference. Conclusion. The information needs outlined in the present study can serve as a general model to help clinical decision makers and policymakers in order to better understand the needs of the group and meet the information needs of the population. Implications for Cancer Survivors. These recommendations can promote and develop targeted interventions to reduce the psychosocial consequences of breast cancer survivors and increase their quality of life.

目的本综述旨在确定乳腺癌幸存者的主要信息需求。由于已有多篇综述涉及这一主题,因此进行总括综述不仅可以综合这些综述的结果,还能全面了解乳腺癌幸存者的需求,并为其提供信息摘要。方法。从开始到 2024 年 3 月底,在 PubMed、Embase、Scopus、Web of Science、ProQuest、Cochrane 和 Google Scholar 中进行了检索。本综述根据 JBI 总综述方法进行,报告以 Rutten 对癌症患者信息需求的分类为基础。在删除重复和不相关的文章后,14 篇系统综述被纳入分析。评估符合条件的文章质量时使用了 JBI 检查表。结果。信息需求被分为 11 个主要类别和 86 个子类别。通过此次总体综述,在 Rutten 的 10 个类别中增加了一个类别。此外,治疗信息需求也被列为主要类别。支持性护理需求信息排在第二位,身体形象/性需求信息排在第三位,但两者略有不同。结论本研究中列出的信息需求可以作为一个通用模型,帮助临床决策者和政策制定者更好地了解群体需求,满足人群的信息需求。对癌症幸存者的启示。这些建议可以促进和发展有针对性的干预措施,以减少乳腺癌幸存者的社会心理后果,提高他们的生活质量。
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引用次数: 0
ERCC3 Gene Associated with Breast Cancer: A Genetic and Bioinformatic Study 与乳腺癌相关的 ERCC3 基因:基因与生物信息学研究
IF 1.9 4区 医学 Q3 OBSTETRICS & GYNECOLOGY Pub Date : 2024-07-14 DOI: 10.1155/2024/7278636
Xiangyu Chen, Heng Xiao, Shuangcheng Ning, Bang Liu, Huashan Zhou, Ting Fu

Female breast cancer is the most common and the fifth deadliest cancer worldwide. It is influenced by a combination of genetic, hormonal, and environmental factors. The excision repair cross-complementation group 3 gene (ERCC3) has recently been identified as a breast cancer susceptibility gene in various cohorts of different geographical and ethnic origin. To explore the role of ERCC3 mutations in breast cancer development and pathological diagnosis, genetic analysis was conducted in 291 patients and 291 controls from mainland China. Bioinformatic analysis and immunohistochemistry (IHC) were performed. A novel ERCC3 mutation p.Y116X was identified in a breast cancer family, while no frequency bias for the genotype and allele of rs754010782 and rs371627165 was observed (all P > 0.05). Bioinformatic analysis revealed that ERCC3 expression was negatively associated with estrogen receptor (ER), progesterone receptor (PR), nontriple-negative status, and nodal status of breast cancers. ERCC3 amplifications and deep deletions primarily occurred in breast invasive cancer not otherwise specified (NOS) and metaplastic breast cancer, respectively. The decreased ERCC3 expression in tumor tissues of patient with p.Y116X mutation was found by IHC. The ERCC3 mutation p.Y116X may increase breast cancer risk in the Han-Chinese population. ERCC3 exhibits potential as a biomarker for the pathological diagnosis of breast cancer.

女性乳腺癌是全球最常见的癌症,也是第五大致命癌症。它受到遗传、激素和环境因素的综合影响。切除修复交叉互补组 3 基因(ERCC3)最近在不同地域和种族的人群中被确定为乳腺癌易感基因。为了探讨ERCC3基因突变在乳腺癌发病和病理诊断中的作用,我们对来自中国大陆的291名患者和291名对照者进行了基因分析。研究还进行了生物信息分析和免疫组化(IHC)。在一个乳腺癌家族中发现了一个新的ERCC3突变p.Y116X,而rs754010782和rs371627165的基因型和等位基因没有频率偏差(均为P> 0.05)。生物信息学分析表明,ERCC3的表达与乳腺癌的雌激素受体(ER)、孕激素受体(PR)、非三阴状态和结节状态呈负相关。ERCC3扩增和深部缺失分别主要发生在未另作规定的乳腺浸润癌(NOS)和移行细胞乳腺癌中。IHC检测发现,p.Y116X突变患者的肿瘤组织中ERCC3表达减少。ERCC3突变p.Y116X可能会增加汉族人群患乳腺癌的风险。ERCC3具有作为乳腺癌病理诊断生物标志物的潜力。
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引用次数: 0
Breast Desmoid Tumours: A Review of the Literature 乳腺蝶形肿瘤:文献综述
IF 1.9 4区 医学 Q3 OBSTETRICS & GYNECOLOGY Pub Date : 2024-07-12 DOI: 10.1155/2024/5803290
Mike Wu, Thomas Michael Hughes, Senarath Edirimanne, Nicholas Ngui

Breast desmoid tumour is a rare type of benign breast disease that presents like malignancy. Current guidelines are based on limited evidence derived from case reports and small case series and recommend resection with microscopically-negative margin (R0). There is a high risk of recurrence despite negative surgical margins. A review of the published cases of breast desmoid since 2000 was conducted using Medline and Embase to descriptively analyse the clinical presentation, diagnosis, treatment, and outcomes of this rare disease. After screening, we identified 46 patients from 39 articles. Most cases did not have risk factors, but 17/46 (37%) had prior procedures on the ipsilateral breast. Mammography was able to detect 65% of the cases, ultrasound detected 74%, and both CT and MRI detected all cases when used. Preoperative diagnosis was best performed using core needle biopsy showing typical histology and positive beta-catenin staining. 42/46 cases underwent definitive surgical management, with 8 cases of recurrence. Recurrence occurred within 3 years of the initial surgery. Median time of recurrence was 8 months, and the median follow-up of the recurrence-free patients was 12 months. There were no predictive factors identified for recurrence. There were 7 cases treated with a nonsurgical modality, with 3 showing at least a partial response.

乳腺蝶形瘤是一种罕见的良性乳腺疾病,表现与恶性肿瘤相似。目前的指南是基于病例报告和小型病例系列中的有限证据,建议在显微镜下边缘阴性(R0)的情况下进行切除。尽管手术切缘阴性,但复发的风险很高。我们利用Medline和Embase对2000年以来发表的乳腺脓肿病例进行了回顾,以描述性分析这种罕见疾病的临床表现、诊断、治疗和结果。经过筛选,我们从 39 篇文章中发现了 46 名患者。大多数病例没有危险因素,但有17/46(37%)的患者曾在同侧乳房做过手术。乳腺放射摄影能发现 65% 的病例,超声波能发现 74% 的病例,CT 和核磁共振成像能发现所有病例。术前诊断的最佳方法是进行核心针活检,显示典型的组织学特征和β-catenin染色阳性。42/46的病例接受了明确的手术治疗,其中8例复发。复发发生在首次手术后的 3 年内。中位复发时间为8个月,无复发患者的中位随访时间为12个月。没有发现复发的预测因素。有 7 例患者接受了非手术治疗,其中 3 例至少出现了部分反应。
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引用次数: 0
Targeted Treatment of Metastatic Triple-Negative Breast Cancer: A Systematic Review 转移性三阴性乳腺癌的靶向治疗:系统性综述
IF 1.9 4区 医学 Q3 OBSTETRICS & GYNECOLOGY Pub Date : 2024-07-11 DOI: 10.1155/2024/9083055
Anna Martha Hammershøi Madsen, Rikke Helene Løvendahl Eefsen, Dorte Nielsen, Iben Kümler

Introduction. Triple-negative breast cancer (TNBC) is a subgroup of breast cancer characterized by the absence of estrogen and the human epidermal 2 receptor and also a lack of targeted therapy options. Chemotherapy has so far been the only approved treatment option, and patients with metastatic cancer have a dismal prognosis with a median overall survival (OS) of approximately 14 months. Identification of druggable targets for metastatic TNBC is therefore of special interest. Methods. A systematic search was performed, to review the existing evidence on targeted therapies in metastatic TNBC. Results. A total of 37 phase 2/3 studies were identified, evaluating 29 different targeted agents. In this review, results on progression free survival (PFS) and OS are presented. Conclusion. In most of the studies included, no improvement was observed for neither PFS nor OS; however, a few studies did show improvement with targeted agents and have led to new treatment options in subgroups of patients. The antibody drug conjugate, sacituzumab govitecan, demonstrated superior PFS and OS in comparison to chemotherapy. Immunotherapy with checkpoint inhibitors such as atezolizumab and pembrolizumab is now recommended as a first-line treatment option for patients with expression a PD-L1 positive tumor. Finally, the poly adenosine diphosphate-ribose polymerase (PARP) inhibitors talazoparib and olaparib are recommended, as first-line treatment options in patients with metastatic breast cancer and a germline BRCA mutation, but an immune checkpoint inhibitor should be considered for the subset of these patients who are PD-L1 positive.

简介三阴性乳腺癌(TNBC)是乳腺癌的一个亚组,其特点是缺乏雌激素和人类表皮2受体,也缺乏靶向治疗选择。迄今为止,化疗是唯一获得批准的治疗方案,而转移性癌症患者的预后很差,中位总生存期(OS)约为 14 个月。因此,确定转移性 TNBC 的可治疗靶点特别重要。研究方法对转移性 TNBC 靶向疗法的现有证据进行系统检索。结果。共确定了 37 项 2/3 期研究,评估了 29 种不同的靶向药物。本综述介绍了无进展生存期(PFS)和OS的结果。结论在纳入的大多数研究中,PFS 和 OS 均未见改善;但也有少数研究显示靶向药物的治疗效果有所改善,并为亚组患者带来了新的治疗选择。与化疗相比,抗体药物共轭物sacituzumab govitecan的PFS和OS均有改善。阿特珠单抗(atezolizumab)和彭博单抗(pembrolizumab)等检查点抑制剂的免疫疗法现已被推荐为表达 PD-L1 阳性肿瘤患者的一线治疗方案。最后,建议将聚腺苷二磷酸核糖聚合酶(PARP)抑制剂talazoparib和olaparib作为转移性乳腺癌和种系BRCA突变患者的一线治疗方案,但对于PD-L1阳性的这些患者中的一部分,应考虑使用免疫检查点抑制剂。
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引用次数: 0
Upregulated SAE1 Drives Tumorigenesis and Is Associated with Poor Clinical Outcomes in Breast Cancer 上调的 SAE1 驱动肿瘤发生并与乳腺癌的不良临床预后有关
IF 1.9 4区 医学 Q3 OBSTETRICS & GYNECOLOGY Pub Date : 2024-06-29 DOI: 10.1155/2024/2981722
Hong Liu, Jing Wang, Yunhai Li, Feng Luo, Lei Xing

Background. The purpose of this study was to analyze SUMO activating enzyme subunit 1 (SAE1) expression in breast cancer (BC). Through bioinformatics analysis and in vitro experiments, the biological function and possibly associated signal pathways of SAE1 in BC were further analyzed. Methods. Bioinformatics analysis was applied to analyze SAE1 expression in BC and normal breast tissues, its relationship with clinicopathologic characteristics and prognosis in BC patients, and data from the Cancer Genome Atlas database and Gene Expression Omnibus dataset. We performed immunohistochemistry to analyze SAE1 expression in BC tissues and para-cancer tissues in 79 breast cancer patients. BC cell proliferation was detected with the Cell Counting Kit-8 and by the colony formation assay. Cell cycle progression was analyzed by flow cytometry, and the expression of cell cycle-related proteins (E2F1, cyclin D3, and cyclin-dependent kinase 2) was determined by western blots in SAE1 small interfering RNA (siRNA) transfected cells. The GSE1456 dataset was used to analyze possible signal pathways associated with SAE1 by gene set enrichment analysis (GSEA), and the expression of PI3K/AKT/mTOR pathway-related proteins (such as p-PI3K, p-AKT, and mTOR) in SAE1-siRNA cells was detected by western blots. Results. The bioinformatics and immunohistochemical results showed that SAE1 mRNA and protein expression in BC tissues were significantly higher than those in normal tissues. The SAE1 overexpression was significantly associated with the tumor size, tumor-node-metastasis stage, estrogen receptor, progesterone receptor, human epidermal growth factor receptor 2, and whether or not it was a triple-negative BC. Patients with SAE1 overexpression had a worse overall survival (OS), recurrence-free survival (RFS), and distant metastasis-free survival compared with lower expression patients. Multivariate Cox regression analysis showed that SAE1 may be an independent prognostic factor for OS of BC patients. The proliferation and cell cycle process of BC cells were inhibited by SAE1-siRNA in vitro. The result of GSEA showed that SAE1 was significantly associated with 12 gene sets, including unfolded protein reaction, DNA repair, oxidative phosphorylation, and cell cycle, among others. Additionally, two signal pathways, mTORC1 and PI3K/Akt/mTOR, were significantly correlated with SAE1 overexpression. Western blots confirmed that the expression of PI3K/Akt/mTOR pathway-related proteins (p-PI3K, p-AKT, and mTOR) in BC cells was decreased after knocking down SAE1. Conclusion. SAE1 was highly expressed in BC. Its overexpression was associated with poor BC prognosis. Additionally, it was an independent prognostic factor for BC patients. We demonstrated that in vitro SAE1 knockdown effectively inhibited BC proliferation and its cell cycle process. Furthermore, the biological function of SAE1 may be associated with the PI3K/Akt/mTOR pathwa

研究背景本研究旨在分析 SUMO 激活酶亚基 1(SAE1)在乳腺癌(BC)中的表达。通过生物信息学分析和体外实验,进一步分析 SAE1 在 BC 中的生物学功能和可能相关的信号通路。研究方法应用生物信息学分析方法分析 SAE1 在 BC 和正常乳腺组织中的表达、其与 BC 患者临床病理特征和预后的关系,以及癌症基因组图谱数据库和基因表达总集数据集的数据。我们用免疫组化方法分析了79例乳腺癌患者的BC组织和癌旁组织中SAE1的表达情况。用细胞计数试剂盒-8 和集落形成试验检测 BC 细胞的增殖情况。流式细胞术分析了细胞周期的进展,Western印迹测定了SAE1小干扰RNA(siRNA)转染细胞中细胞周期相关蛋白(E2F1、细胞周期蛋白D3和细胞周期蛋白依赖性激酶2)的表达。利用基因组富集分析(GSE1456)数据集分析与SAE1相关的可能信号通路,并通过Western印迹检测PI3K/AKT/mTOR通路相关蛋白(如p-PI3K、p-AKT和mTOR)在SAE1-siRNA细胞中的表达。结果生物信息学和免疫组化结果显示,SAE1 mRNA和蛋白在BC组织中的表达量明显高于正常组织。SAE1的过表达与肿瘤大小、肿瘤-结节-转移分期、雌激素受体、孕激素受体、人表皮生长因子受体2以及是否为三阴性BC明显相关。与低表达患者相比,SAE1过表达患者的总生存期(OS)、无复发生存期(RFS)和无远处转移生存期均较差。多变量Cox回归分析表明,SAE1可能是影响BC患者OS的一个独立预后因素。SAE1-siRNA在体外抑制了BC细胞的增殖和细胞周期过程。GSEA结果显示,SAE1与12个基因组显著相关,包括未折叠蛋白反应、DNA修复、氧化磷酸化和细胞周期等。此外,mTORC1和PI3K/Akt/mTOR这两个信号通路与SAE1的过表达有明显相关性。Western 印迹证实,在敲除 SAE1 后,PI3K/Akt/mTOR 通路相关蛋白(p-PI3K、p-AKT 和 mTOR)在 BC 细胞中的表达量减少。结论SAE1在BC细胞中高表达。SAE1的过表达与BC的不良预后有关。此外,它还是 BC 患者的一个独立预后因素。我们证实,体外敲除 SAE1 能有效抑制 BC 增殖及其细胞周期过程。此外,SAE1的生物学功能可能与PI3K/Akt/mTOR通路有关。SAE1将成为治疗BC的潜在靶点。
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引用次数: 0
Causes of Unwarranted Variation and Disparity in Breast Cancer Management in Regional and Rural Area 区域和农村地区乳腺癌管理中无端差异和差距的原因
IF 2.1 4区 医学 Q2 Medicine Pub Date : 2024-06-19 DOI: 10.1155/2024/9354395
Kimberley J. Davis, Chantal Campbell, Rebekah Costelloe, Ting Song, Glaucia Fylyk, Ping Yu, Steven J. Craig

Introduction. Breast cancer management is complex, requiring personalised care from multidisciplinary teams. Research shows that there is unwarranted clinical variation in mastectomy rates between rural and metropolitan patients; that is, variation in treatment which cannot be explained by disease progression or medical necessity. This study aims to determine the clinical and nonclinical factors contributing to any unwarranted variation in breast cancer management in rural patients and to evaluate how these factors and variations relate to patient outcomes. Methods. Comprehensive data from patients who had primary breast cancer surgery from 2010 to 2014 in either a rural or metropolitan location in a single local health district was analysed (n = 686). Records were subset into two rurality groupings based on the postcode in which the patient resided, and the Modified Monash Model (MMM), an Australian system for classifying rurality. Statistical analysis was used to compare rural and metropolitan cohorts on treatments, patient characteristics, timeliness, and outcomes (recurrence and survival). Results. Rural patients had higher mastectomy rates than metropolitan patients (57% vs. 34%, p < 0.001), despite a lack of difference in clinical or demographic factors accounting for such variation. The length of time between treatment pathway stages was consistently longer amongst rural patients (p < 0.01). Rural women also had worse survival outcomes, especially amongst HER2-positive patients who had significantly lower survival (5-year 74% vs 82%; 10-year 49% vs 71%, p < 0.05) than metropolitan HER2-positive patients. Conclusion. This study reveals clinical disparities among rural breast cancer patients, that cannot be explained by demographic and clinical factors alone. Rural patients face lower rates of breast-conserving surgery and treatment delays, attributable to systemic barriers such as limited access to specialist care, high travel costs, and suboptimal care coordination. These findings have important implications for improving equity and collaboration in delivering person-centred breast cancer care.

简介乳腺癌的治疗非常复杂,需要多学科团队提供个性化护理。研究表明,农村和城市患者的乳房切除率存在不必要的临床差异;也就是说,疾病进展或医疗必要性无法解释治疗上的差异。本研究旨在确定导致农村患者乳腺癌治疗出现不必要差异的临床和非临床因素,并评估这些因素和差异与患者预后的关系。研究方法分析了 2010 年至 2014 年期间在一个地方卫生区的农村或城市地区接受乳腺癌初治手术的患者的综合数据(n = 686)。根据患者居住地的邮政编码和澳大利亚乡村分类系统 "改良莫纳什模型"(MMM),将记录分成两个乡村分组。统计分析用于比较乡村组和城市组的治疗方法、患者特征、及时性和结果(复发率和存活率)。结果显示农村患者的乳房切除率高于城市患者(57% vs. 34%, p <0.001),尽管造成这种差异的临床或人口学因素缺乏差异。在农村患者中,治疗路径阶段之间的间隔时间一直较长(p <0.01)。农村妇女的生存率也更低,尤其是HER2阳性患者的生存率(5年74% vs 82%;10年49% vs 71%,p < 0.05)明显低于城市HER2阳性患者。结论。这项研究揭示了农村乳腺癌患者的临床差异,而这些差异不能仅用人口和临床因素来解释。农村患者接受保乳手术和治疗延误的比例较低,这归因于系统性障碍,如获得专科护理的机会有限、旅行成本高以及护理协调不理想。这些发现对改善以人为本的乳腺癌护理的公平性和协作性具有重要意义。
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引用次数: 0
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Breast Journal
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