Identification of an immune classifier for predicting the prognosis and therapeutic response in triple-negative breast cancer

Triple-negative breast cancer(TNBC)poses a significant challenge due to the lack of reliable prognostic gene signatures and an understanding of its immune behavior.Methods:We analyzed clinical information and mRNA expression data from 162 TNBC patients in TCGA-BRCA and 320 patients in METABRIC-BRCA.Utilizing weighted gene coexpression network analysis,we pinpointed 34 TNBC immune genes linked to survival.The least absolute shrinkage and selection operator Cox regression method identified key TNBC immune candidates for prognosis prediction.We calculated chemotherapy sensitivity scores using the“pRRophetic”package in R software and assessed immunotherapy response using the Tumor Immune Dysfunction and Exclusion algorithm.Results:In this study,34 survival-related TNBC immune gene expression profiles were identified.A least absolute shrinkage and selection operator-Cox regression model was used and 15 candidates were prioritized,with a concomitant establishment of a robust risk immune classifier.The high-risk TNBC immune groups showed increased sensitivity to therapeutic agents like RO-3306,Tamoxifen,Sunitinib,JNK Inhibitor VIII,XMD11-85h,BX-912,and Tivozanib.An analysis of the Search Tool for Interaction of Chemicals database revealed the associations between the high-risk group and signaling pathways,such as those involving Rap1,Ras,and PI3K-Akt.The low-risk group showed a higher immunotherapy response rate,as observed through the tumor immune dysfunction and exclusion analysis in the TCGA-TNBC and METABRIC-TNBC cohorts.Conclusion:This study provides insights into the immune complexities of TNBC,paving the way for novel diagnostic approaches and precision treatment methods that exploit its immunological intricacies,thus offering hope for improved management and outcomes of this challenging disease.

Male metaplastic breast cancer with poor prognosis:A case report

BACKGROUND Metaplastic breast cancer(MBC)is a rare subtype of breast cancer.They constitute less than 1%of breast cancer cases and are much rarer in males.There are few reports of MBC because of its rarity.MBC,an aggressive type of cancer,is refractory to common treatment modalities of breast cancer and has a poor prognosis.CASE SUMMARY We report a case of MBC in a 78-year-old man.He visited our clinic with a palpable mass on the left breast with no masses in the axillary areas.He had previously undergone robot-assisted laparoscopic radical prostatectomy for prostate cancer,but there was no family history of malignancy.The breast mass was visible on ultrasonography,mammography,and magnetic resonance imaging,and chest computed tomography revealed a lung mass in the posterior basal segment of the right lower lobe.The patient was diagnosed with metaplastic carcinoma on core needle biopsy with lung metastasis.Total mastectomy with sentinel lymph node biopsy and video-assisted segmentectomy of the right lung was performed.However,multiple metastases appeared 3 mo after surgery in the brain,chest,and abdomen,and the patient died 5 mo after the initial diagnosis.CONCLUSION MBC is an aggressive and extremely rare breast cancer type.Further case reports are needed to determine the optimal treatment.

Male Breast Cancer Clinical Features, Risk Factors, and Current Diagnostic and Therapeutic Approaches

Objective: To review presentation, diagnosis, treatment and prognosis of male breast cancer. Method: A systematic review of the English language literature between 1990 and 2013 was conducted to identify studies relevant to the objective. Searches were carried out on the database PubMed, by using the title term “male breast cancer”. Results: The majority of male patients present with a painless, firm, subareolar lump. Experience of male breast imaging is good but limited. However, there is no definitive therapeutic algorithm. Men are often treated with mastectomy instead of breast conserving surgery and mostly tamoxifen is used as an adjuvant therapy. The most important prognostic factors are tumor size and lymph node status in the armpit. Conclusion: More increased awareness and further research are needed to improve the diagnosis and treatment of this disease.

MALE BREAST CANCER: A REPORT OF 34 CASES

Objective： To study the biological characteristics, the therapeutic procedure and the prognosis of male breast cancer. Methods： 34 patients with male breast cancer were retrospectively analyzed, who were diagnosed and treated in the First Hospital of Jilin University between 1980 and March 2005. Results： Clinical TNM stage of the patients were stage Ⅰ, 6 patients, stage Ⅱ, 24 patients and stage Ⅲ, 4 patients＇. Positive lymph nodes were found in 35.3% of the patients. All these patients received modified radical mastectomy. The 5-year survival rate was 65.3%. Postoperation recurrence rate was 11.8%. Conclusions： Patients with male breast cancer should receive surgical treatment, assisted with adjuvant treatment, such as radiotherapy, chemotherapy, endocrine therapy and so on. TNM stage and expression of hormone receptor may be the main factors affecting the prognosis.

基于SEER数据库构建和验证男性乳腺癌预后模型

目的探究男性乳腺癌(male breast cancer,MBC)患者的预后因素,构建MBC患者生存预后列线图并预测3年和5年生存率。方法纳入监测、流行病学和最终结果(Surveillance,Epidemiology,and End Results,SEER)癌症登记数据库的MBC患者,同时纳入川北医学院附属医院、遂宁市中心医院和德阳市人民医院的MBC患者,获取患者完整的临床基线资料及生存信息。以SEER数据库中患者数据作为训练集,3家医院中的患者数据作为验证集,通过单因素和多因素Cox回归分析确定与总生存期(overall survival,OS)相关的独立预后因素,并构建预测MBC患者3年及5年生存率的列线图,运用校准曲线、一致性指数(CI)、受试者工作特征曲线(ROC)和决策分析曲线来评估模型的准确程度和实际应用价值。结果共纳入3387名MBC患者,其中训练集3307例,验证集80例。通过对训练集进行单因素和多因素Cox回归分析后发现,诊断年龄、组织学分级、T分期、N分期、M分期、孕激素受体状态、手术、化疗和放疗是影响MBC患者OS的独立预后因素。将这些因素纳入并构建列线图模型并进行验证,训练集CI为0.711,验证集CI为0.787。训练集中,3年OS的AUC为0.744,5年OS的AUC为0.720;验证集中,3年OS的AUC为0.835,5年OS的AUC为0.858。ROC曲线表明模型区分能力较好,校准曲线显示模型预测性能良好,决策分析曲线表明模型的临床应用价值较高。结论开发的列线图为预测MBC患者的预后提供了一种可靠且实用的方法,有助于个性化治疗决策,改善患者的治疗效果。

78例男性乳腺癌患者的临床病理特征和预后分析

目的探讨男性乳腺癌的临床病理特点及治疗方法,分析影响预后的因素。方法本研究纳入78例男性乳腺癌患者。观察并分析患者的临床病理特点及治疗方法,并对所有患者进行长时间随访。采用单因素分析影响患者生存的因素。结果患者平均年龄为60.5岁,激素受体阳性率高达91%,HER-2阳性率仅为12.8%,Ki-67低表达患者比例为74.5%。所有患者总的5年生存率为80.8%。T1、T2期患者的生存预后优于T3、T4期患者(P=0.023)。有淋巴结转移的患者总生存期较无淋巴结转移的患者低(P=0.027);Ⅰ、Ⅱ期患者总生存期较Ⅲ、Ⅳ期患者好(P<0.001)。结论男性乳腺癌患者相对年龄较大,激素受体阳性率较高,HER-2、Ki-67表达较低。肿瘤大小、淋巴结状态和TNM分期是影响总生存的重要因素。

槐耳颗粒联合免疫治疗用于晚期三阴性乳腺癌解救治疗的临床分析

目的探究槐耳颗粒联合免疫治疗用于晚期三阴性乳腺癌解救治疗的临床获益及安全性。方法收集2019年11月至2021年12月期间就诊于沧州市中心医院的PD-L1表达阳性的晚期三阴性乳腺癌患者67例进行回顾性分析,按照所接受的治疗方案不同分为对照组(n=33)和观察组(n=34)。对照组患者采用卡瑞利珠单抗^(+)白蛋白结合型紫杉醇的治疗方案;观察组在对照组方案基础上加用槐耳颗粒。治疗完成后比较两组患者的临床疗效、卡氏功能状态(Karnofsky Performance Status,KPS)评分变化情况、肿瘤标志物水平、T淋巴细胞亚群水平、预后情况以及不良反应发生情况。结果治疗后,观察组患者的疾病控制率高于对照组(73.53%vs 48.48%);卡氏评分提高率高于对照组(52.94%vs 15.15%);观察组的CD4^(+)T淋巴细胞比例及CD4^(+)/CD8^(+)均高于对照组,CD8^(+)T淋巴细胞比例低于对照组;观察组的中位PFS长于对照组[13.41个月(95%CI:11.62,15.19)vs 9.53个月(95%CI:7.76,11.30)];观察组的中位OS长于对照组[16.38个月(95%CI:14.51,18.25)和12.02个月(95%CI:10.52,13.51)];观察组的血小板减少和免疫性肺炎的发生率均低于对照组。以上差异均具有统计学意义(P<0.05)。结论槐耳颗粒联合免疫治疗用于晚期三阴性乳腺癌的解救治疗具有较好的临床疗效,且改善了患者生活质量,改善了患者预后,安全性较好。

Grey zone in the Barcelona Clinic Liver Cancer Classification for hepatocellular carcinoma: Surgeons' perspective

Hepatocellular carcinoma(HCC) is the sixth most common cancer and the third most common cause of cancer-related deaths worldwide. The Barcelona Clinic Liver Cancer(BCLC) classification has been endorsed as the optimal staging system and treatment algorithm for HCC by the European Association for the Study of Liver Disease and the American Association for the Study of Liver Disease. However, in real life, the majority of patients who are not considered ideal candidates based on the BCLC guideline still were performed hepatic resection nowadays, which means many hepatic surgeons all around the world do not follow the BCLC guidelines. The accuracy and application of the BCLC classification has constantly been challenged by many clinicians. From the surgeons' perspectives, we herein put forward some comments on the BCLC classification concerning subjectivity of the assessment criteria, comprehensiveness of the staging definition and accuracy of the therapeutic recommendations. We hope to further discuss with peers and colleagues with the aim to make the BCLC classification more applicable to clinical practice in the future.

An appropriate treatment interval does not afect the prognosis of patients with breast Cancer

Purpose:Major public health emergencies may lead to delays or alterations in the treatment of patients with breast cancer at each stage of diagnosis and treatment.How much do these delays and treatment changes afect treatment outcomes in patients with breast cancer?Methods:This review summarized relevant research in the past three decades and identifed the efect of delayed treatment on the prognosis of patients with breast cancer in terms of seeking medical treatment,neoadjuvant treatment,surgery,postoperative chemotherapy,radiotherapy,and targeted therapies.Results:Delay in seeking medical help for≥12weeks afected the prognosis.Surgical treatment within 4 weeks of diagnosis did not afect patient prognosis.Starting neoadjuvant chemotherapy within 8 weeks after diagnosis,receiving surgical treatment at 8 weeks or less after the completion of neoadjuvant chemotherapy,and receiving radiotherapy 8 weeks after surgery did not afect patient prognosis.Delayed chemotherapy did not increase the risk of relapse in patients with luminal A breast cancer.Every 4 weeks of delay in the start of postoperative chemotherapy in patients with luminal B,triple-negative,or HER2-positive breast cancer treated with trastuzumab will adversely afect the prognosis.Targeted treatment delays in patients with HER2-positive breast cancer should not exceed 60days after surgery or 4months after diagnosis.Radiotherapy within 8 weeks after surgery did not increase the risk of recurrence in patients with early breast cancer who were not undergoing adjuvant chemotherapy.Conclusion:Diferent treatments have diferent time sensitivities,and the careful evaluation and management of these delays will be helpful in minimizing the negative efects on patients.

老年三阴性乳腺癌患者的临床困境和系统治疗策略

三阴性乳腺癌(triple-negative breast cancer,TNBC)缺乏明确的生物标志物,现有治疗手段以化疗为主,疗效有限且不良反应大。10%~21%的TNBC为老年患者,多伴随心、脑、肾疾病等诸多慢性合并症,对化疗耐受性差,是临床诊疗实践的一大难题。同时,专门针对老年TNBC患者的临床研究较少,导致这部分患者的安全及合理用药缺乏充足的循证医学证据,在疾病诊疗方面存在很多难点和争议。此外,老年TNBC有其特征,非肿瘤因素所致死亡率较高。因此,患者生存获益与生活质量及耐受性之间的平衡尤为重要。本文主要针对老年TNBC的流行病学、疾病生物学行为及特征、诊疗现状及未被满足的治疗需求等进行总结分析,并初步探索新型抗体药物偶联物(antibody-drug conjugate,ADC)在老年TNBC中的获益,以期为老年TNBC系统治疗策略的选择提供参考。

G蛋白偶联雌激素受体对乳腺癌患者预后和临床病理的影响:系统荟萃分析

目的本研究对G蛋白偶联雌激素受体(GPER)在乳腺癌中的表达及其对预后的作用进行荟萃分析,以了解GPER表达对乳腺癌患者生存和临床病理特征的影响。方法使用相同的搜索策略在2022年11月24日更新的电子数据库中搜索相关文献。提取个体风险比(HR)和优势比(OR)及其95%CI并合并,使用Review Manager 5.4.1评估GPER阳性表达与乳腺癌患者生存结果和临床病理特征之间的关联强度,同时进行异质性和敏感性分析。Begg's检验、Egger's检验和漏斗图用于评估发表偏差。结果GPER表达对乳腺癌患者OS有有利影响(HR=0.77,95%CI:0.49-1.22,Z=1.10,P=0.27),对DFS/RFS/DDFS有不利影响(HR=1.03,95%CI:0.64-1.65,Z=0.13,P=0.90),但差异均无统计学意义。GPER表达与乳腺癌患者的预后无显著相关性,GPER表达不是BC患者的独立预后因素。此外,GPER的表达与TNM分期(OR=0.31,95%CI:0.06-0.55,Z=2.43,P=0.02)、远处转移(OR=6.82,95%CI:1.89-24.55,Z=2.94,P=0.003)、组织学分级(OR=0.009,95%CI:-0.16-0.01,Z=2.16,P=0.03)、ER表达(OR=1.77,95%CI:1.15-2.72,Z=2.59,P=0.009)和PR表达(OR=1.36,95%CI:1.00-1.84,Z=1.95,P=0.005)有关。结论GPER可能不是乳腺癌的独立预后因素。此外,GPER表达与乳腺癌患者的TNM分期、远处转移、组织学分级、ER表达和PR表达显著相关。

MRI影像组学在乳腺癌新辅助化疗中的应用进展

乳腺癌是女性最常见的恶性肿瘤,其发病率和死亡率呈逐年上升趋势。新辅助化疗(neoadjuvant chemotherapy,NAC)已成为当前乳腺癌综合治疗中重要组成部分,不同类型乳腺癌对NAC治疗后的反应、预后不同。磁共振(magnetic resonance imaging,MRI)影像组学可以从MRI图像中提取大量定量特征,结合高通量计算对数据进行分析,获取全面的肿瘤信息并应用于乳腺癌NAC疗效的预测及评价。近年来有大量研究探讨了影像组学在乳腺癌NAC中的临床应用,包括预测乳腺癌分子亚型、对NAC的反应、预后因素及复发风险。由于缺乏统一的标准化定义及可重复性限制了影像组学的临床应用,但MRI影像组学仍具有广阔的发展前景。本文旨在将对MRI影像组学在乳腺癌NAC疗效和预后中的应用进展、面临的问题及应用前景进行综述,为乳腺癌精准化治疗决策提供新思路。

Chinese female breast cancer patients show a better overall survival than their male counterparts

Backgroud It is not clear if there is a difference in prognosis between male breast cancer （MBC） and female breast cancer （FBC） patients. The aim of this study was to compare the prognosis of MBC and FBC patients in China and the prognosis of MBC and their corresponding postmenopausal FBC patients.Methods Thirty-five MBC patients who were treated at the Sun Yat-sen University Cancer Center between 1969 and 2004 were enrolled in the study. Seventy FBC patients who were matched with the MBC patients for TNM stage, year of diagnosis, and age at diagnosis were simultaneously enrolled in the study. A second group comprising 18 MBC patients and their corresponding 36 matched postmenopausal FBC patients were also enrolled. The whole group and the postmenopausal groups were compared for five- and ten-year survivals. Results All the factors that could potentially affect prognosis were comparable among the groups except more FBC than MBC patients underwent endocrine therapy and a modified radical mastectomy. The 5- and 10-year survivals in the whole group were 81.6% and 60.3% for men and 90.7% and 73.5% for women （P=0.02）. The 5- and 10-year survival in the postmenopausal group was 82.5% and 100% for men and 66.0% and 85.9% for women （P=0.159）.Conclusions Chinese FBC patients had a better prognosis than Chinese MBC patients. However, MBC patients and their corresponding postmenopausal FBC patients had a similar prognosis.

TMEM家族在乳腺癌中的研究进展

跨膜蛋白(transmembrane protein,TMEM)基因家族广泛参与细胞膜结构的组成,如内质网、溶酶体和高尔基体。研究发现TMEM蛋白在乳腺癌的发生发展过程中发挥重要作用,具有促癌和(或)抑癌的双重功能。TMEM不仅参与调控乳腺癌细胞的增殖、侵袭和迁移等,同时与化疗耐药有关。因此,更好地表征TMEM家族成员在乳腺癌中的表达情况、临床意义和预后价值,探索其功能可以为肿瘤的预防和治疗提供新的思路。

HER2阳性早期乳腺癌全身治疗变革及未来展望

近二十年来,随着HER2靶向药物的出现和发展,HER2阳性早期乳腺癌的生存率得到了显著提升。如何优化治疗模式和治疗策略,使患者达到最佳获益,是HER2阳性早期乳腺癌治疗领域的研究热点。本文将通过对HER2阳性早期乳腺癌新辅助和辅助治疗阶段的重要临床研究进行概述及分析,以期为未来制定HER2阳性早期乳腺癌的个体化治疗策略提供参考。

软骨素聚合因子在乳腺癌中的研究进展

乳腺癌是全世界女性最常见的癌症,已成为全球性的健康问题。肿瘤学最新领域的研究揭示了软骨素聚合因子(CHPF)在乳腺癌各种生物学行为方面的潜在作用。CHPF是一种Ⅱ型跨膜蛋白,是一种参与硫酸软骨素(chondroitin sulfate,CS)延伸的酶,是许多癌症预后不良的新关键分子。目前,CHPF在乳腺癌发生发展中的机制成为研究热点。未来,深入探究CHPF在乳腺癌中的作用及其分子机制,可为乳腺癌的防治及靶向治疗提供新思路。本文将概述CHPF及其在各种恶性肿瘤中的作用,着重介绍CHPF在乳腺癌中的生物功能,有望为抗肿瘤药物研究提供新的治疗靶点,为肿瘤治疗提供新思路。

影响男性乳腺癌预后的多因素分析——单中心72例临床资料总结

背景与目的:中国男性乳腺癌的报道大多是小样本、回顾性研究,而分析影响患者预后因素的报道极少。本研究在相对比较大样本的中国男性乳腺癌资料基础上探讨影响患者预后的因素。方法:收集1969年1月至2009年3月在中山大学肿瘤防治中心经病理确诊、随访资料齐全的72例男性乳腺癌患者的临床资料。采用Kaplan-Meier方法、log-rank检验和Cox回归模型分析影响男性乳腺癌患者预后的因素。结果:本组男性乳腺癌患者的5年总生存率为72.4%,其中Ⅰ期100%,Ⅱ期74.2%、Ⅲ期57.2%、Ⅳ期0。单因素分析显示,肿瘤大小(P<0.001)、腋窝淋巴结转移(P=0.001)、TNM分期(P=0.001)、手术方式(手术和非手术比较:P<0.001;经典根治术和改良根治术比较:P=0.336)、有无内分泌治疗(P=0.02)是影响男性乳腺癌预后的因素。Cox多因素模型分析显示,TNM分期(P=0.035)、手术与否(P=0.021)、有无内分泌治疗(P=0.019)是影响预后的主要因素。结论:TNM分期、手术与否和有无内分泌治疗是影响中国男性乳腺癌预后的重要因素,提示早期发现和以手术为主、包含有内分泌治疗的综合治疗模式是提高男性乳腺癌患者生存率的关键手段之一。

70岁以上老年浸润性乳腺癌患者的临床病理特点、治疗现状及预后分析

目的分析70岁以上老年女性浸润性乳腺癌患者的临床及病理特点、治疗方式、生存情况及影响预后的因素。方法收集178例70岁以上老年浸润性乳腺癌患者的临床资料、随访生存情况,统计分析其临床病理特点、生存率及影响治疗方案选择和预后的因素。结果全组178例患者,83.7%的患者合并至少一种伴随疾病。T1、T2期患者分别占46.1%、36.5%,多为浸润性导管癌,ER和(或)PR阳性的患者占81.6%。多因素分析显示肿瘤大小、淋巴结转移、TNM分期、PR状态、并发症情况、腋窝手术方式是影响患者是否接受化疗的独立因素;年龄是影响患者是否接受放疗的唯一独立因素。中位随访51月,3、5年无病生存率分别为91.8%和80.5%,3年的总生存率为94%。肿瘤大小、淋巴结转移情况、TNM分期、是否行手术治疗是影响老年浸润性乳腺癌患者生存的影响因素。治疗不足,尤其是化疗不足会影响老年患者生存,但结果差异未见统计学意义。结论老年浸润性乳腺癌以早期患者为主,预后较好,影响治疗的主要因素集中在肿瘤分期、分子分型及年龄并发症情况。多数患者死亡原因为非乳腺癌相关原因,手术治疗仍是提高患者生存的主要干预手段。

男性乳腺癌的临床研究进展

男性乳腺癌发病罕见,过去25年间发病率呈上升趋势。目前对男性乳腺癌生物学、自然病程以及治疗策略的研究大部分是基于对女性乳腺癌的研究成果。男性乳腺癌的发病风险因素包括BRCA2基因突变和职业因素,而职业因素又包括高温工作环境、燃料和尾气;此外,性激素失衡,如生殖腺功能失调、肥胖、辐射等均可增加患病风险。临床病情进展可缓慢或快速转移。病理类型绝大多数为导管癌,10%为导管原位癌。常采取的手术是乳房切除术和腋窝淋巴结清扫或前哨淋巴结活检术。放疗步骤和方法同女性乳腺癌。由于90%的男性乳腺癌患者雌激素受体阳性,因此他莫昔芬是标准的辅助内分泌治疗药物,个别病例也可从化疗中获益。本文对近年有关男性乳腺癌的流行病学、生物学和治疗方面的相关内容进行总结。

男性乳腺癌的临床病理特征及生存分析

目的探讨男性乳腺癌患者的临床病理特征及影响预后的因素。方法回顾性分析1999年1月至2010年5月经病理证实的55例接受手术治疗的男性乳腺癌患者。采用Kaplan-Meier法绘制生存曲线,Log-rank检验进行生存比较,多因素分析用Cox风险比例回归模型。结果 55例患者的5年生存率为61.8%。肿瘤TNM分期Ⅰ、Ⅱ、Ⅲ和Ⅳ期患者的5年生存率分别为75.0%、69.6%、45.4%和20.0%,差异有统计学意义（P〈0.05）。组织学分级Ⅰ、Ⅱ和Ⅲ级患者的5年生存率分别为83.3%、67.5%和33.3%,差异有统计学意义（P〈0.05）。单因素分析显示,不同组织学分级、T分期、TNM分期、淋巴结有无转移及是否放疗均与男性乳腺癌患者的5年生存率有关（P〈0.05）。Cox回归模型分析显示,组织学分级（HR=3.690,95%CI：1.476-9.225,P〈0.05）和TNM分期（HR=3.437,95%CI：1.447-8.163,P〈0.05）是影响男性乳腺癌预后的独立因素。结论组织学分级和TNM分期是影响男性乳腺癌预后的独立因素。男性乳腺癌的诊治有待进一步研究。