曲妥珠单抗治疗HER2+乳腺癌的临床进展

临床研究显示曲妥珠单抗与化疗联合用于人表皮生长因子受体2(HER2)+转移性乳腺癌的治疗以及早期乳腺癌的新辅助和辅助治疗,能显著延长患者的生存时间.其与内分泌治疗联合治疗HER2+且雌激素受体阳性的转移性乳腺癌,疗效优于单纯内分泌治疗.曲妥珠单抗联合其他靶向治疗药物,能够逆转肿瘤对曲妥珠单抗的耐药.疾病进展后继续应用曲妥珠单抗仍可使患者生存受益.     

HER⁃2阳性乳腺癌免疫治疗药物的研究进展

曲妥珠单抗及帕妥珠单抗等药物的应用使HER?2阳性乳腺癌患者的生存得到了显著的提高,但靶向药耐药事件仍时有发生.免疫治疗作为一种新的治疗手段,对HER?2阳性乳腺癌患者具有重大临床意义.作为被动免疫治疗的一种有效手段,单克隆抗体曲妥珠单抗、帕妥珠单抗及T?DM1等药物的临床应用使HER?2阳性乳腺癌患者的生存有了明显改...     

人表皮生长因子受体2阳性乳腺癌应用新辅助治疗的疗效及影响因素分析

目的 分析人表皮生长因子受体2(HER2)阳性乳腺癌应用新辅助治疗的疗效及影响因素。方法 选取47例HER2阳性乳腺癌患者,均接受曲妥珠单抗和帕妥珠单抗联合紫杉类+卡铂新辅助治疗。比较不同激素受体（HR）表达情况乳腺癌患者的临床特征,HER2阳性乳腺癌患者新辅助治疗总病理学完全缓解（tpCR）的影响因素采用Logistic回归分析。结果 47例HER2阳性乳腺癌患者中,HR阴性19例,HR阳性28例,HR阳性患者年龄≤50岁、月经状态为绝经前比例均明显高于HR阴性患者,乳腺病理学完全缓解（bpCR）率、tpCR率和客观缓解率（ORR）均明显低于HR阴性患者,差异均有统计学意义（P﹤0.01）。47例接受曲妥珠单抗和帕妥珠单抗联合紫杉类+卡铂新辅助治疗患者的tpCR率为70.21%(33/47),单因素分析结果显示,HER2阳性乳腺癌患者新辅助治疗的tpCR可能与雌激素受体（ER）和孕激素受体（PR）表达状态有关（P﹤0.01）;多因素Logistic回归分析结果显示,ER表达情况、PR表达情况均不是HER2阳性乳腺癌患者新辅助治疗tpCR的影响因素（P﹥0.05）。结论曲妥珠单抗和帕妥...     

HER2阳性乳腺癌治疗的研究进展

[摘要] 人表皮生长因子受体2（human epidermal growth factor receptor 2,HER2）阳性乳腺癌侵袭性高,预后差。随着抗HER2药物的不断出现及广泛应用,HER2 阳性乳腺癌患者的预后出现了非常显著的改善。10 年随访结果证实1 年曲妥珠单抗辅助治疗可以显著降低疾病复发风险;对于术后的高危人群,曲妥珠单抗联合帕妥珠单抗或者曲妥珠单抗序贯来那替尼可以进一步减少复发。5 年随访结果表明帕妥珠单抗+曲妥珠单抗为基础的新辅助治疗可使病理完全缓解（pathological complete response,pCR）转化为长期生存获益;白蛋白紫杉醇代替普通紫杉醇与抗HER2 药物联用可以进一步提高pCR率;而抗HER2 药物联合内分泌治疗尚不能达到与联合化疗在新辅助治疗中疗效,即使联合CDK4/6 抑制剂,对于pCR的提高依然有限。曲妥珠单抗+帕妥珠单抗联合紫杉类药物是晚期HER2 阳性乳腺癌的标准一线方案;对于老年、体弱的患者,节拍环磷酰胺可以作为紫杉类药物的替代品;拉帕替尼+曲妥珠单抗联合内分泌治疗可以作为HER2 阳性伴激素受体阳性的选择,疗效优于曲妥珠单抗联合内分泌治疗;T-DM1 无论是作为二线治疗还是三线及以后的治疗均提高了患者生存获益,是治疗晚期、耐药HER2阳性乳腺癌的首选。     

帕妥珠单抗在HER-2阳性乳腺癌治疗中的临床转化

帕妥珠单抗(pertuzumab)作为一种新的抗人表皮生长因子受体-2(human epidermal growth factor receptor,HER-2)治疗药物,其作用区域不同于曲妥珠单抗,两者联合可以发挥更全面的HER-2抑制作用,基础和临床转化研究均证实帕妥珠单抗和曲妥珠单抗有协同的抗肿瘤作用.Ⅱ期和Ⅲ期临床转化试验结果显示,抗HER-2两药治疗(帕妥珠单抗+曲妥珠单抗)联合化疗可使HER-2阳性晚期乳腺癌的中位无疾病进展时间(progression-free survival,PFS)延长到18个月以上,中位总生存时间(overall survival,OS)接近5年(56.5个月),显著改善了晚期HER-2阳性乳腺癌患者的预后.两项Ⅱ期新辅助治疗临床转化研究也确认帕妥珠单抗联合曲妥珠单抗的协同作用疗效同样突出,病理完全缓解(pathological complete response,pCR)率最高可达66.2％.安全性分析发现,即使是与蒽环类药物联用,加用帕妥珠单抗治疗也并未增加心脏毒性.本文对帕妥珠单抗在HER-2阳性乳腺癌治疗中的上述相关临床转化研究进行综述.     

基于免疫微环境特征的曲妥珠单抗与免疫治疗联合应用预测模型

背景与目的：人表皮生长因子受体2(human epidermal growth factor receptor 2,HER2)阳性乳腺癌患者的肿瘤免疫微环境（tumor immune microenvironment,TIME）与曲妥珠单抗治疗效果显著相关，提示免疫检查点疗法联合曲妥珠单抗治疗的临床潜力。本研究旨在探索HER2阳性乳腺癌联合治疗的预测因子，筛选联合治疗的潜在获益人群。方法：纳入高通量基因表达（Gene Expression Omnibus,GEO）数据库中509例接受曲妥珠单抗治疗的HER2阳性乳腺癌患者和癌症基因组图谱（The Cancer Genome Atlas,TCGA）数据库中67例HER2阳性乳腺癌患者的转录组与基因组数据，筛选曲妥珠单抗耐药组的差异表达基因进行功能富集分析、蛋白质互作网络构建。结合临床信息通过对数秩检验和多因素COX比例风险回归模型构建预测模型。并利用CIBERSORT反卷积法分析TIME特征，通过肿瘤免疫功能障碍和排斥（tumor immune dysfunction and exclusion,TIDE）评分预测免疫治疗获益。结果：通过...     

曲妥珠单抗一线治疗66例HER2阳性转移性乳腺癌的疗效和安全性分析

摘 要：［目的］ 探讨曲妥珠单抗一线治疗人表皮生长因子受体2（HER2）阳性转移性乳腺癌患者的疗效和安全性。［方法］ 回顾性分析66例曲妥珠单抗联合化疗药物一线治疗HER2阳性转移性乳腺癌患者的临床疗效和不良反应。心脏功能的变化采用彩色超声心动图监测左心室射血分数（LVEF）。 ［结果］ 66例患者中,完全缓解（CR）3例（4.54%）,部分缓解（PR）52例（78.79%）,疾病稳定（SD）9例（13.64%）,疾病进展（PD）2例（3.03%）,客观有效率（ORR）为83.33%（55/66）。中位无进展生存期(mPFS)为12.0个月,中位总生存期（OS）为38.0个月,1、2、3、5、10年生存率为98.5%、80.3%、57.6%、30.3%和11.4%。单因素及多因素分析显示,转移灶的数量是影响PFS的独立因素（P＜0.05）,转移灶的数量、曲妥珠单抗累积使用时间是影响OS的独立因素（均P＜0.05）。曲妥珠单抗治疗相关的不良反应主要表现为心脏功能的下降,最重为3级LVEF下降,发生率为1.5%（1例）。［结论］ 曲妥珠单抗一线治疗HER2阳性转移性乳腺癌患者疗效明显且安全。小负荷转移病灶及早并长期应用曲妥珠单抗治疗,能给患者带来生存获益。     

含曲妥珠单抗二线治疗HER2阳性乳腺癌的临床价值及安全性分析

目的探讨含曲妥珠单抗二线治疗人表皮生长因子受体2(HER2)阳性乳腺癌的临床价值及安全性。方法选择采用二线方案治疗的78例HER2阳性乳腺癌患者为研究对象,根据患者治疗方式不同分为A组与B组。2组患者均接受吉西他滨联合卡培他滨二线治疗方案,B组患者同时接受曲妥珠单抗治疗。比较2组近期疗效、2年生存率及不良反应发生率。结果 A组与B组治疗有效率及临床获益率均无显著差异(P>0.05);B组2年生存率显著优于A组(P<0.05)。骨髓抑制及消化道不良反应是2组常见的化疗不良反应;曲妥珠单抗的主要不良反应为发热及疼痛,经对症治疗后均完成治疗。结论含曲妥珠单抗二线治疗方案治疗HER2阳性乳腺癌可延长患者生存期,安全性好。     

HER2阳性乳腺癌治疗的研究进展

人表皮生长因子受体2(HER2)阳性乳腺癌因其侵袭性高、预后差而一直备受关注。随着曲妥珠单抗的应用,早期HER2阳性乳腺癌患者的预后已得到显著改善,由于其仍存在耐药性和不良反应,在标准治疗中加入新的抗HER2药物又成为新的研究重点,这些药物包括帕妥珠单抗、抗体药物偶联物曲妥珠单抗-美坦新(T-DM1)和各种小分子抑制剂(拉帕替尼、来那替尼、吡咯替尼)。同时PD1及PD-L1抑制剂如帕博利珠单抗在HER2阳性乳腺癌中的研究也在进行中,并有部分基础研究和病例报道已经证实了其疗效和安全性。本文旨在对目前HER2阳性乳腺癌的治疗方案和支持HER2阳性乳腺癌治疗的最新证据进行综述。     

肿瘤相关炎性因子对曲妥珠单抗治疗HER2阳性转移性乳腺癌预后及疗效的影响

目的 研究肿瘤相关炎性因子(tumor associated inflammatory factor,TAIF)对曲妥珠单抗治疗人表皮生长因子受体2(HER2)阳性转移性乳腺癌(PMBC)预后及疗效的关系.方法 选取接受曲妥珠单抗方案治疗的HER2 PMBC患者89例纳入为试验组,选取同期接受健康体检的健康女性89例纳入为对照组,试验组所有患者均给予卡培他滨、吉西他滨联合曲妥珠单抗治疗,观察化疗前两组及试验组化疗前后的TNF-α、IL-1β、IL-6、IL-8水平,试验组的临床疗效,并对影响曲妥珠单抗治疗HER2 PMBC患者预后的因素进行多因素回归分析.结果治疗后,试验组的RR为40.45％,DCR为69.66％,1年内复发、转移率为79.78％.化疗前,试验组的TNF-α、IL-1β、IL-6、IL-8水平均明显高于对照组(P﹤0.01).试验组化疗前的TNF-α、IL-1β、IL-6、IL-8水平均明显高于化疗后(P﹤0.01).化疗前后,试验组1年内复发、转移患者的TNF-α、IL-1β、IL-6、IL-8水平均高于未复发、转移患者(P﹤0.05).年龄、身高、体重不是影响曲妥珠单抗治疗HER2 PMBC患者预后的危险因素(P﹥0.05);TNF-α、IL-1β、IL-6、IL-8是影响曲妥珠单抗治疗HER2 PMBC患者预后的危险因素(P﹤0.05).结论 TAIF可促进HER2 PMBC的进展、复发及转移,影响曲妥珠单抗治疗HER2 PMBC患者的疗效及预后.     

Predictive role of hand-foot syndrome in patients receiving capecitabine plus bevacizumab for HER2-negative locally recurrent/metastatic breast cancer北大核心CSCD

Objective: To observe the correlation between hand-foot syndrome (HFS) and prognosis of patients with human epidermal growth factor receptor 2 (HER2)- negative locally recurrent/metastatic breast cancer (LR/mBC) receiving chemotherapy with capecitabine (CAP) plus bevacizumab (BEV). Methods: One hundred patients with HER2-negative LR/mBC receiving first-line CAP plus BEV were divided into HFS group and non-HFS group, then the relationship between HFS and clinicopathologic characteristics of patients with HER2-negative LR/mBC and the related factors influencing the progression-free survival (PFS) and overall survival (OS) were analyzed by COX proportional hazards model. Results: There were statistically significant differences in menopausal status and the number of metastatic organs between HFS group and non-HFS group (all P < 0.05). The median PFS of the HFS group was significantly longer than that of the non-HFS group (10.7 months vs 5.8 months, P = 0.007). The median survival time of the HFS group was also significantly longer than that of the non-HFS group (22.8 months vs 14.9 months, P < 0.001). There was an association of Eastern Cooperative Oncology Group (ECOG) performance status (PS) score, hormone receptor status, metastasis at first diagnosis, metastatic organ site, the number of metastases and HFS with PFS (all P < 0.05). ECOG PS score, hormone receptor status, metastasis at first diagnosis, metastatic organ site and HFS were independent risk factors for PFS (all P < 0.05). There was an association of menopausal status, ECOG PS score, hormone receptor status, metastasis at first diagnosis, the number of metastatic organ and HFS with OS (all P < 0.05). Menopausal status, hormone receptor status, metastasis at first diagnosis, and HFS were independent risk factors for OS (all P < 0.05). Conclusion: HFS can be used as a predictor of therapeutic effect of HER2-negative LR/mBC patients receiving CAP-BEV. The patients with HFS have a better prognosis than patients without HFS. Copyright © 2017 by TUMOR All rights reserved.     

Is triple negative a prognostic factor in breast cancer?

Background  Breast cancer is characterized by hormone dependency, and endocrine therapy is a key treatment in breast cancer. Recently, targeted therapies such as Trastuzumab treatment for HER2-positive breast cancer has been important. Triple-negative (TN) breast cancer is characterized by lack of expression of estrogen receptor (ER) and progesterone receptor (PgR), and the absence of HER2 protein overexpression, and so there is no targeted therapy for this subtype. In this study, we examined the biological and prognostic characteristics in TN breast cancer. Patients and methods  Between January 1998 and September 2006, 1,552 patients with primary breast cancer were investigated retrospectively in this study and ER, PgR and HER2 status were evaluated in all cases. Furthermore, p53 overexpression and Ki67 values were examined immunohistochemically. Results  Patient distribution according to ER, PgR or HER2 status was as follows: ER and PgR positive: 57.9%, and ER and PgR negative: 25.1%. With regards to the HER2 status, HER2 positive was 23.3%, and triple negative (TN) was 14.0%. TN breast cancer has a high proliferation rate, high nuclear grade and frequent p53 overexpression. Patients with TN tumors had a significantly poorer disease-free survival (DFS) than those with non-TN tumors. After recurrence the overall survival (OS) rate in TN cases was significantly lower than that of the non-TN cases. Multivariate analysis revealed that TN was a significant factor for DFS and OS after recurrence. Conclusion  TN breast cancer is a rare subtype with a high proliferation rate and a high nuclear grade, p53 overexpression, and lower DFS/OS. To improve the prognosis of TN breast cancer, a new effective strategy needs to be developed.     

54例乳腺癌术后胸壁转移患者的临床特征及预后因素分析

目的：探讨乳腺癌术后局部胸壁转移患者的临床特征、治疗方式及影响预后的因素。方法收集54例术后以胸壁复发为首发转移部位的乳腺癌患者的临床资料,分析各项临床和病理因素同局部控制率及生存期之间的关系;并搜索万方及Pubmed数据库中的相关文献,进行汇总分析。结果54例患者原发肿瘤术后无病生存期（DFS）为4～277个月,中位DFS为50个月。单纯胸壁转移患者局部复发后无进展生存期（PFS）2～120个月,中位PFS为21个月。单纯胸壁转移组的单因素分析结果显示患者的原发肿瘤病理类型、脉管癌栓情况、激素受体水平、HER2表达情况是原发肿瘤术后DFS及OS的相关预后因素;多因素分析结果显示原发肿瘤的病理类型、脉管癌栓情况、术后辅助放疗、辅助内分泌治疗及原发肿瘤术后DFS是总生存期的独立预后因素。结论乳腺癌术后局部复发将增加远处转移及死亡风险,明确高复发风险因素,采取全身综合治疗及局部治疗可改善患者预后。     

曲妥珠单抗联合拉帕替尼及多西紫杉醇一线治疗HER-2阳性晚期乳腺癌的安全性和有效性

目的:观察曲妥珠单抗联合拉帕替尼及多西紫杉醇一线治疗HER-2阳性晚期乳腺癌的安全性和有效性。方法:这是一项前瞻、单臂、开放标签的单中心Ⅱ期临床研究(ChiCTR1800015814)。HER-2阳性晚期乳腺癌一线治疗给予曲妥珠单抗(6 mg/kg,首剂8 mg/kg)联合拉帕替尼(1 000 mg/d)及多西紫杉醇(75 mg/m2),每3周重复。对非进展的患者继续用药直至疾病进展或毒性不可耐受,但最长用药时间不超过2年。主要研究终点是有效率,次要终点是PFS和OS。结果:自2016年9月至2019年5月共入组65例患者。本方案的剂量限制性毒性为腹泻,Ⅲ-Ⅳ度腹泻发生率为24.6%。总体有效率为69.2%(CR 3.1%,PR 66.1%),激素受体阴性患者有效率明显优于激素受体阳性患者(76.7% vs 57.1%,P＜0.01)。中位随访31个月,PFS为16.4个月(95%CI:13.4~19.6个月)。尚未达到中位OS时间。Log-rank检验显示是否内脏转移、是否多器官转移对PFS的影响具有统计学意义(P＜0.01和P=0.022)。结论:曲妥珠单抗联合拉帕替尼及多西紫杉醇毒性可耐受,疗效较好,作为HER-2阳性晚期乳腺癌一线治疗新的治疗策略,值得进一步研究。     

The efficacy of HER2-targeted agents in metastatic breast cancer: a meta-analysis

BackgroundThe addition of HER2-targeted agents to standard treatment has been shown to improve outcomes for HER2 positive metastatic breast cancer patients. We undertook a meta-analysis to evaluate the efficacy of HER2-targeted therapy in addition to standard treatment in metastatic breast cancer patients.Patients and methodsEligible trials were randomised controlled trials (RCTs) comparing the addition of HER2 therapy to standard treatment (hormone or chemotherapy) reporting overall survival (OS), time to progression (TTP), progression-free survival (PFS) and/or response rates.ResultsEight trials comprising 1848 patients were eligible for inclusion. HER2-targeted agents were trastuzumab and lapatinib and therapeutic partners were taxanes (4 RCTs), anthracyclines (1), capecitabine (2), anastrozole (1) and letrozole (1). The addition of HER2-targeted agents improved OS [hazard ratios (HR) 0.78; 95% confidence interval (CI) 0.67–0.91], TTP (HR 0.56; 95% CI 0.48–0.64), PFS (HR 0.63; 95% CI 0.53–0.74) and overall response rate (relative risk 1.67; 95% CI 1.46–1.90).ConclusionsOur meta-analysis confirms the benefit of adding HER2-targeted therapy to standard treatment in HER2 positive metastatic breast cancer. Compared with OS, TTP, PFS and ORR overestimate treatment benefit. Trials in our meta-analysis differed in terms of partner drug or HER2 agents, yet delivered comparable outcomes.     

African American patients with breast cancer have worse prognosis than white patients in certain subtypes and stages

Purpose

Racial disparity of breast cancer in each subtype and substage is not clear.

Methods

We reviewed 156,938 patients with breast cancer from 2010 to 2012 from the National Cancer Institute Surveillance, Epidemiology, and End Results database. Breast cancer was subtyped by hormone receptor (HR) and human epidermal growth factor 2 (HER2) status as HR+/HER2?, HR+/HER2+, HR?/HER2+, and HR?/HER2?.

Results

African American (AA) patients had worse overall survival (OS) and breast cancer cause-specific survival (BCSS) in HR+/HER2? stages III and IV breast cancer and HR?/HER2+ stage IV cancer; they had worse OS but not BCSS in HR+ /HER2? stage II cancer and HR?/HER2? stage II cancer.

Conclusion

AA patients with breast cancer had worse survival in certain subtype and stage, especially in ER+ breast cancer.

     

Prognostic factors of survival in the trastuzumab era among women with breast cancer and brain metastases who receive whole brain radiotherapy

BACKGROUND:

The objective of this study was to review the outcome of women with breast cancer with known receptor status who were treated with whole brain radiotherapy for brain metastases and to determine factors that impact survival.

METHODS:

A total of 223 women with breast cancer and brain metastases, who received whole brain radiotherapy, were identified. All women with HER‐2–positive disease had received trastuzumab. Kaplan‐Meier product limit method was used to determine overall survival (OS) estimates. Cox proportional hazards models were then fitted to explore the association of OS with various patient and tumor characteristics.

RESULTS:

Median age at brain metastases diagnosis was 50 years. Sixty‐seven (30.2%) patients had hormone receptor‐positive/HER‐2–negative disease, 101 (45.50%) had HER‐2–positive disease, and 54 (24.3%) had triple receptor‐negative disease. Median OS from brain metastases was 6 months, with 1‐year survival of 30% (95% confidence interval [CI], 23%‐36%). Women with hormone receptor‐positive/HER‐2–negative, HER‐2–positive, and triple‐negative tumors had median survivals of 5, 9, and 5 months, respectively (P = .0069). In the multivariate model, women with HER‐2–positive disease had a significantly decreased risk of death compared with women with hormone receptor‐positive/HER‐2–negative disease (hazard ratio, 0.63; 95%CI, 0.42‐0.94; P = .02). The risk of death among women with triple‐negative disease compared with hormone receptor‐positive/HER‐2–negative disease was not significantly different (P = .54). Lower recursive partitioning analysis class and ≥30‐gray brain radiation dose were also significantly associated with a decreased risk of death.

CONCLUSIONS:

Breast tumor subtype has a significant prognostic role among women with breast cancer and brain metastases. In addition, in the trastuzumab era factors such as recursive partitioning analysis and adequate radiation dose continue to be important prognostic factors. Cancer 2010. © 2010 American Cancer Society.     

85例颅外转移性乳腺癌放疗疗效观察及预后分析

目的 观察颅外转移性乳腺癌的放疗疗效,探讨全病变放疗意义及预后相关因素。方法 回顾性分析2014—2019年间接受放疗的 85例颅外转移性乳腺癌患者的临床资料,其中全病变放疗 36例,非全病变放疗 49例。采用Kaplan-Meier法计算生存率并log-rank检验和单因素预后分析,Cox模型多因素预后分析。结果 全组中位随访时间26.7个月,2年局控(LC)、无进展生存(PFS)、总生存(OS)率分别为77%、26%、77%。全病变放疗预后显著优于非全病变放疗,2年LC率分别为91%和67%(P=0.001),2年PFS率分别为47%和8%(P<0.001),2年OS率分别为84%和71%(P=0.010)。多因素分析显示全病变放疗是LC、PFS、OS的独立预后因素。此外,接受放疗时是否仅有骨转移是LC的影响因素,激素受体状态是OS的影响因素。结论 全病变放疗可以延长颅外转移性乳腺癌患者的生存。仅有骨转移的患者接受放疗后LC更佳,激素受体阴性的患者长期生存较差。     

ER和PR阴性乳腺癌雄激素受体与HER2表达相关性及其临床意义

目的 激素受体阴性(ER-/PR-)乳腺癌具有明显的肿瘤异质性,临床治疗手段相对有限.本研究探讨激素受体阴性乳腺癌组织中,雄激素受体(androgen receptor,AR)和HER2表达的相关性,及其与临床病理参数和预后的相关性.方法 收集中国人民解放军福州总医院经手术治疗并病理确诊的乳腺癌120例,中位年龄52岁.采用FISH法检测收集的激素受体阴性乳腺癌组织HER2/neu基因状态,分为HER2阳性(HER2过表达组)和HER2阴性(三阴组)两组,每组60例.并采用EliVisionTM plus免疫组化法检测AR、Ki-67、EGFR表达,分析HER2和AR表达与临床病理参数、3年无病生存期(disease free survival,DFS)的相关性.结果 AR在激素受体阴性乳腺癌组织阳性率为61.67％(74/120),HER2过表达组和三阴组分别为73.33％(44/60)和50.00％(30/60).激素受体阴性乳腺癌组织中,AR表达与月经状态、肿瘤大小、组织学分级、EGFR表达及HER2状态相关,均P值＜0.05;在HER2过表达组中,AR表达与月经状态、淋巴结受累、EGFR表达相关,均P值＜0.05;三阴组中,AR表达与肿瘤大小和组织学分级相关,均P值＜0.05.Kaplan-Meier法分析显示,HER2过表达组中AR表达与患者的3年DFS呈正相关,P＜0.05;Cox回归法分析结果示,肿瘤大小、淋巴结受累、EGFR表达、AR表达均与患者的3年DFS有关,P＜0.05.结论 AR可能成为筛选激素受体阴性乳腺癌高危人群和预测其预后的辅助指标之一,可作为激素受体阴性乳腺癌的新治疗靶点,为不同HER2状态乳腺癌治疗提供新思路.     

Trastuzumab Retreatment after Relapse on Adjuvant Trastuzumab Therapy for Human Epidermal Growth Factor Receptor 2-Positive Breast Cancer: Final Results of the Retreatment after Herceptin Adjuvant Trial

AimsTrastuzumab, in combination with chemotherapy, is the standard of care for patients with early and metastatic human epidermal growth factor receptor 2 (HER2)-positive breast cancer. The Retreatment after HErceptin Adjuvant trial assessed the efficacy and safety of trastuzumab plus a taxane as first-line treatment for patients with metastatic breast cancer (MBC) who had relapsed after adjuvant trastuzumab for HER2-positive early breast cancer.Materials and methodsIn total, 43 patients with HER2-positive MBC who had received previous adjuvant trastuzumab for ≥10 months, with a relapse-free interval of ≥6 months after the last adjuvant trastuzumab dose, were recruited. Eligible patients (n = 41) were assigned to receive trastuzumab, either weekly or every 3 weeks, in combination with docetaxel or paclitaxel until disease progression.ResultsAt the final analysis, with a median follow-up time of 40 months, a positive response was observed in 25/41 patients (61%; 95% confidence interval: 48.7–80.4%), stable disease in 7/41 (17.1%) and progressive disease in 6/41 (14.6%). Three patients had missing response assessments (one had no measurable lesions at baseline and two had no post-baseline tumour assessments). The median progression-free survival (PFS) was 8.0 months (95% confidence interval: 6–11 months) and the median overall survival was 25.0 months (16–33 months). No correlation was found between response rate, PFS or overall survival and the duration of adjuvant trastuzumab treatment, trastuzumab-free interval, relapse-free interval, hormone receptor status or type of pre-metastatic treatment. The most common adverse events (all grades) were alopecia (32%) and diarrhoea (32%). Six patients (14.6%) developed at least one serious adverse event. No congestive heart failure or any unexpected adverse events were reported.ConclusionTrastuzumab, in combination with a taxane, is an effective and well-tolerated first-line treatment for MBC in patients who relapse after trastuzumab-based adjuvant therapy.