【作者】 王丽君；

【导师】 胡崇珠；

【作者基本信息】 承德医学院 ， 外科学（专业学位）， 2024， 硕士

【摘要】 目的:了解在真实世界临床实践中曲妥珠单抗加帕妥珠单抗联合紫杉类药物（trastuzumab plus pertuzumab combined with taxanes,THP）方案新辅助治疗HER-2阳性乳腺癌的应用状况,评价该方案的疗效、安全性、耐受性,为THP方案的合理应用提供参考依据。方法:选择2019年6月1日至2021年12月31日在保定市第一中心医院、河北大学附属医院、秦皇岛市第一医院等河北省多个地市11家三级甲等医院接受以曲妥珠单抗加帕妥珠单抗（trastuzumab plus pertuzumab,HP）为基础方案新辅助治疗并完成后续手术的HER-2阳性乳腺癌患者为研究对象,接受THP方案新辅助治疗患者为研究组,接受HP配伍联合化疗方案（TCb HP方案或AC-THP方案）新辅助治疗患者为对照组。制订专用的患者资料信息收集表,专人负责信息收集,回顾性收集符合纳入标准患者的临床病理资料。分析THP方案的应用状况、病理完全缓解（pathological complete response,p CR）率、严重不良反应发生率、既定治疗方案完成率,比较两组患者的p CR率、严重不良反应发生率和既定治疗方案完成率。结果:共纳入180例患者,其中70例（38.9%）患者接受THP方案治疗（THP组）,110例（61.1%）患者接受TCb HP方案或AC-THP方案治疗（联合化疗组）。患者均为女性。THP组平均年龄55.44（±10.22）岁,中位年龄为55.5岁（31岁～74岁）。联合化疗组平均年龄51.14（±9.76）岁,中位年龄53岁（27岁～68岁）。THP组伴有合并疾病患者的比例高于联合化疗组,差别有统计学意义（52.9%vs 26.4%,χ²=12.930,P<0.001）。其余临床病理因素两组患者无显著差别。THP组的p CR率为54.3%（38/70）,其中11.4%（8/70）为yp T_isyp N₀,42.9%（30/70）为yp T₀yp N₀。亚组分析显示,激素受体阴性、HER-2 IHC3+、c TNMⅠ-Ⅱ期患者的p CR率显示出高于激素受体阳性、HER-2 IHC2+/FISH+、c TNMⅢ期患者的趋势,但差异无统计学意义（65.7%vs 42.9%,χ²=3.684,P=0.055;57.8%vs 16.7%,χ²=2.204,P=0.121;64.7%vs 44.4%,χ²=2.893,P=0.089）。联合化疗组的p CR率为61.8%。THP组的p CR率低于联合化疗组,但差异无统计学意义（54.3%vs 61.8%,χ²=1.003,P=0.317）。THP组严重不良反应发生率为4.3%（3/70）,低于联合化疗组（11.8%,13/110）,差异无统计学意义（χ²=2.997,P=0.083）。THP组既定治疗方案完成率为98.6%（69/70）,高于联合化疗组（91.8%,101/110）,差异有显著性（χ²=7.915,P=0.007）。结论:THP方案在河北省各地市的真实世界临床实践中得到广泛应用。THP方案是HER-2阳性乳腺癌新辅助治疗的有效方案,安全性及耐受性良好,在激素受体阴性、HER-2蛋白过表达（IHC3+）、肿瘤负荷较小（c TNMⅠ-Ⅱ期）患者中显示出较为明显的p CR率增加趋势。HER2+/HR-患者可能是THP方案的适宜人群。THP方案可以考虑作为激素受体阴性、HER-2蛋白过表达（IHC3+）、肿瘤负荷较小、对联合化疗耐受性差的HER-2阳性乳腺癌患者新辅助治疗的备选方案。更多还原

【Abstract】 Objective:To understand the application status of trastuzumab plus pertuzumab combined with taxanes（THP）regimen in real world clinical practice,and evaluate the efficacy,safety and tolerability of this regimen,so as to provide reference for the rational application of the THP regimen.Methods:Patients with HER-2 positive breast cancer who received trastuzumab plus pertuzumab（HP）-based neoadjuvant therapy and completed subsequent surgery in 11 tertiary-level A municipal hospitals in Hebei Province from June 1,2019 to December 31,2021,including the Baoding First Central Hospital,the Affiliated Hospital of Hebei University,and the First Hospital of Qinhuangdao et al,were selected as the study population.Patients who received neoadjuvant therapy with THP regimen were selected as the study group,and patients received neoadjuvant therapy with HP-matched combination chemotherapy regimens（TCb HP or AC-THP）were the control group.A special patient data collection form was developed,and personnel were responsible for retrospectively collecting the clinicopathologic data of patients who met the inclusion criteria.So as to assess application status,pathological complete response（p CR）rate,incidence of serious adverse reactions and completion rate of the established treatment of the THP regimen,and to compare pathological complete response（p CR）rate,incidence of serious adverse reactions,and completion rate of established neoadjuvant therapy regimen between the two groups of patients.Results:A total of 180 patients were included,70（38.9%）patients recieved the THP regimen（THP group）and 110（61.1%）patients recieved the AC-THP regimen or TCb HP regimen（combination chemotherapy group）.All patients were female.The mean age of the THP group was 55.44（±10.22）years old,and the median age was 55.5 years old（31-74 years old）.The mean age of the combination chemotherapy group was 51.14（±9.76）years old,and the median age was 53 years old（27-68 years old）.The proportion of patients with concurrent diseases in THP group was higher than that in combination chemotherapy group,and the difference was statistically significant（52.9%vs 26.4%,χ²=12.930,P<0.001）.There was no significant difference in other clinicopathological factors between the two groups.The p CR rate of THP group was 54.3%（38/70）,of which 11.4%（8/70）was yp T_isyp N₀and 42.9%（30/70）was yp T₀yp N₀.Subgroup analysis showed that the p CR rate of patients with hormone receptor-negative,HER-2 IHC3+and c TNM stageⅠtoⅡwas higher than that of patients with hormone receptor-positive,low HER-2 IHC2+/FISH+and c TNM stageⅢ.However,the difference was not statistically significant（65.7%vs 42.9%,χ²=3.684,P=0.055;57.8%vs16.7%,χ²=2.204,P=0.121;64.7%vs 44.4%,χ²=2.893,P=0.089）.The p CR rate in the THP group was lower than that in the combined chemotherapy group,but the difference was not statistically significant（54.3%vs 61.8%,χ²=1.003,P=0.317）.The incidence of serious adverse reactions was 4.3%（3/70）in the THP group,which was lower than that in the combination chemotherapy group（11.8%,13/110）,and the difference was not statistically significant（χ²=2.997,P=0.083）.The completion rate of the established regimen in the THP group was 98.6%（69/70）,which was higher than that in the combined chemotherapy group（91.8%,101/110）,with significant difference（χ²=7.915,P=0.007）.Conclusions:THP regimen has been widely used in real-world clinical practice in cities across Hebei Province,which is an effective neoadjuvant therapy regimen for patients with HER-2 positive breast cancer,with good safety and tolerability,showing a more obvious trend of increasing p CR rate in patients with hormone receptor-negative,overexpression of HER-2 protein（IHC3+）,and low tumor burden（c TNM stage I-II）.HER2+/HR-patients may be suitable for THP regimen.Patients with hormone receptor-negative,overexpression of HER-2 protein（IHC3+）,low tumor burden,and poor tolerance to combination chemotherapy may consider THP regimen as an alternative for neoadjuvant therapy.更多还原