他莫昔芬（tamoxifen,TAM）是治疗雌激素受体（estrogen receptor,ER）阳性乳腺癌最有效且应用时间最长的一线内分泌治疗药物,能够有效降低ER阳性乳腺癌患者的死亡率和复发率。然而,临床资料显示约50%的ER阳性乳腺癌患者对内分泌治疗显...他莫昔芬（tamoxifen,TAM）是治疗雌激素受体（estrogen receptor,ER）阳性乳腺癌最有效且应用时间最长的一线内分泌治疗药物,能够有效降低ER阳性乳腺癌患者的死亡率和复发率。然而,临床资料显示约50%的ER阳性乳腺癌患者对内分泌治疗显示出固有耐药,而在对TAM治疗有反应的患者中,30%-40%可发展成获得性耐药。本文从ERα36、G蛋白偶联雌激素受体（G protein-coupled estrogen receptor,GPER）、前梯度蛋白2（anterior gradient 2,AGR2）和乳腺癌扩增性抗原1（amplii ed in breast cancer 1,AIB1）这些与ERα及其信号通路有关的蛋白着眼,阐释ER阳性乳腺癌TAM耐药的机制,以期为ER阳性乳腺癌的治疗提供新思路。展开更多
Objective:This post-approval safety study assessed the efficacy and safety of exemestane after 2-3 years of tamoxifen treatment among postmenopausal women with estrogen receptor-positive(ER+)early breast cancer in Chi...Objective:This post-approval safety study assessed the efficacy and safety of exemestane after 2-3 years of tamoxifen treatment among postmenopausal women with estrogen receptor-positive(ER+)early breast cancer in China.Methods:Enrolled patients had received 2-3 years of tamoxifen and were then switched to exemestane for completion of 5 consecutive years of adjuvant endocrine therapy.The primary endpoint was the time from enrollment to the first occurrence of locoregional/distant recurrence of the primary breast cancer,appearance of a second primary or contralateral breast cancer,or death due to any cause.Other endpoints included the proportion of patients experiencing each event,incidence rate per annum,relationships between human epidermal growth factor receptor 2 status and time to event,and relationship between disease history variables and time to event.Results:Overall,558 patients were included in the full analysis set:397(71.1%)completed the study,20experienced an event,and 141 discontinued[47 owing to an adverse event(AE);37 no longer willing to participate].Median duration of treatment was 29.5(range,0.1-57.7)months.Median time to event was not reached.Eventfree survival probability at 36 months was 91.4%(95%CI,87.7%-95.1%).The event incidence over the total exposure time of exemestane therapy was 3.5 events/100 person-years(20/565).Multivariate analysis showed an association between tumor,lymph node,and metastasis stage at initial diagnosis and time to event[hazard ratio:1.532(95%CI,1.129-2.080);P=0.006].Most AEs were grade 1 or 2 in severity,with arthralgia(7.7%)being the most common treatment-related AE.Conclusions:This study supports the efficacy and safety of exemestane in postmenopausal Chinese women with ER+breast cancer previously treated with adjuvant tamoxifen for 2-3 years.No new safety signals were identified in the Chinese population.展开更多
背景与目的:内分泌治疗已经是激素受体阳性乳腺癌患者手术后辅助治疗的常规手段之一。本研究旨在分析影响可手术乳腺癌患者接受卵巢功能抑制(ovarian function suppression,OFS)治疗后短期效应(雌激素抑制效果)和长期生存(无病生存期)...背景与目的:内分泌治疗已经是激素受体阳性乳腺癌患者手术后辅助治疗的常规手段之一。本研究旨在分析影响可手术乳腺癌患者接受卵巢功能抑制(ovarian function suppression,OFS)治疗后短期效应(雌激素抑制效果)和长期生存(无病生存期)的影响因素。方法:回顾性分析2017年6月—2019年6月于复旦大学附属肿瘤医院行手术且完成术后标准化疗和内分泌治疗(OFS联合他莫昔芬或芳香化酶抑制剂)的435例雌激素受体(estrogen receptor,ER)阳性乳腺癌患者的临床病理学资料和无病生存期(disease-free survival,DFS)。采用单因素和多因素logistic回归分析对雌激素抑制效应有影响的因素,并运用log-rank检验和Cox比例风险回归模型分析对患者DFS有影响的因素。结果:OFS治疗后,年龄≤35岁患者雌激素抑制失败率为8.7%,显著高于35~40岁患者1%的雌激素抑制失败率(P<0.05);不同OFS药物如戈舍瑞林和亮丙瑞林的雌激素抑制作用基本一致(P>0.05)。内分泌治疗方案(HR=0.49,P<0.05)、腋窝淋巴结状态(HR=4.21,P<0.05)和肿瘤直径(HR=2.00,P<0.05)均是患者DFS的独立预后因素;虽然雌激素抑制失败患者倾向预后较差(P=0.10),但不同OFS药物对降低复发转移的疗效也一致。结论:年龄是乳腺癌患者采用OFS治疗后短期雌激素抑制失败的独立危险因素;内分泌药物、腋窝淋巴结状态以及肿瘤直径会影响ER阳性可手术乳腺癌患者的长期预后;无论是戈舍瑞林还是亮丙瑞林对患者降低雌激素水平和长期无病生存期差异无统计学意义。展开更多
文摘他莫昔芬（tamoxifen,TAM）是治疗雌激素受体（estrogen receptor,ER）阳性乳腺癌最有效且应用时间最长的一线内分泌治疗药物,能够有效降低ER阳性乳腺癌患者的死亡率和复发率。然而,临床资料显示约50%的ER阳性乳腺癌患者对内分泌治疗显示出固有耐药,而在对TAM治疗有反应的患者中,30%-40%可发展成获得性耐药。本文从ERα36、G蛋白偶联雌激素受体（G protein-coupled estrogen receptor,GPER）、前梯度蛋白2（anterior gradient 2,AGR2）和乳腺癌扩增性抗原1（amplii ed in breast cancer 1,AIB1）这些与ERα及其信号通路有关的蛋白着眼,阐释ER阳性乳腺癌TAM耐药的机制,以期为ER阳性乳腺癌的治疗提供新思路。
文摘Objective:This post-approval safety study assessed the efficacy and safety of exemestane after 2-3 years of tamoxifen treatment among postmenopausal women with estrogen receptor-positive(ER+)early breast cancer in China.Methods:Enrolled patients had received 2-3 years of tamoxifen and were then switched to exemestane for completion of 5 consecutive years of adjuvant endocrine therapy.The primary endpoint was the time from enrollment to the first occurrence of locoregional/distant recurrence of the primary breast cancer,appearance of a second primary or contralateral breast cancer,or death due to any cause.Other endpoints included the proportion of patients experiencing each event,incidence rate per annum,relationships between human epidermal growth factor receptor 2 status and time to event,and relationship between disease history variables and time to event.Results:Overall,558 patients were included in the full analysis set:397(71.1%)completed the study,20experienced an event,and 141 discontinued[47 owing to an adverse event(AE);37 no longer willing to participate].Median duration of treatment was 29.5(range,0.1-57.7)months.Median time to event was not reached.Eventfree survival probability at 36 months was 91.4%(95%CI,87.7%-95.1%).The event incidence over the total exposure time of exemestane therapy was 3.5 events/100 person-years(20/565).Multivariate analysis showed an association between tumor,lymph node,and metastasis stage at initial diagnosis and time to event[hazard ratio:1.532(95%CI,1.129-2.080);P=0.006].Most AEs were grade 1 or 2 in severity,with arthralgia(7.7%)being the most common treatment-related AE.Conclusions:This study supports the efficacy and safety of exemestane in postmenopausal Chinese women with ER+breast cancer previously treated with adjuvant tamoxifen for 2-3 years.No new safety signals were identified in the Chinese population.
文摘背景与目的:内分泌治疗已经是激素受体阳性乳腺癌患者手术后辅助治疗的常规手段之一。本研究旨在分析影响可手术乳腺癌患者接受卵巢功能抑制(ovarian function suppression,OFS)治疗后短期效应(雌激素抑制效果)和长期生存(无病生存期)的影响因素。方法:回顾性分析2017年6月—2019年6月于复旦大学附属肿瘤医院行手术且完成术后标准化疗和内分泌治疗(OFS联合他莫昔芬或芳香化酶抑制剂)的435例雌激素受体(estrogen receptor,ER)阳性乳腺癌患者的临床病理学资料和无病生存期(disease-free survival,DFS)。采用单因素和多因素logistic回归分析对雌激素抑制效应有影响的因素,并运用log-rank检验和Cox比例风险回归模型分析对患者DFS有影响的因素。结果:OFS治疗后,年龄≤35岁患者雌激素抑制失败率为8.7%,显著高于35~40岁患者1%的雌激素抑制失败率(P<0.05);不同OFS药物如戈舍瑞林和亮丙瑞林的雌激素抑制作用基本一致(P>0.05)。内分泌治疗方案(HR=0.49,P<0.05)、腋窝淋巴结状态(HR=4.21,P<0.05)和肿瘤直径(HR=2.00,P<0.05)均是患者DFS的独立预后因素;虽然雌激素抑制失败患者倾向预后较差(P=0.10),但不同OFS药物对降低复发转移的疗效也一致。结论:年龄是乳腺癌患者采用OFS治疗后短期雌激素抑制失败的独立危险因素;内分泌药物、腋窝淋巴结状态以及肿瘤直径会影响ER阳性可手术乳腺癌患者的长期预后;无论是戈舍瑞林还是亮丙瑞林对患者降低雌激素水平和长期无病生存期差异无统计学意义。
