两种新辅助治疗方案治疗HR阳性、HER-2阳性乳腺癌的疗效及安全性比较

Comparison the efficacy and safety of two kinds of neoadjuvant therapy in HR positive and HER-2 positive breast cancer

目的:比较激素受体(hormone receptor,HR)阳性、人类表皮生长因子受体-2(human epidermal growth factor receptor-2,HER-2)阳性乳腺癌两种新辅助治疗方案的疗效及安全性。方法:采用随机对照方法,纳入我院自2019年04月至2020年06月患者年龄为60岁以上或者60岁以下已绝经,并且病理学确诊的HER-2阳性(3+或者Fish基因扩增)、HR阳性的Ⅱ-Ⅲ期可手术(肿瘤大小>2 cm)的乳腺癌患者。我们按1∶1比例随机分配受试者接受两种不同的新辅助治疗方案,分组如下:化疗组患者接受曲妥珠单抗+帕妥珠单抗+白蛋白紫杉醇+卡铂,内分泌组患者接受曲妥珠单抗+帕妥珠单抗+氟维司群+哌柏西利,并在新辅助治疗完成后4周内进行乳腺癌手术,此后我们采用系统随机方法将两组研究对象按照T分期、淋巴结数目、年龄进行分层,进而比较两组治疗人群术后的病理性完全缓解率(ypT_(0/is),ypN_(0))。结果:13例化疗组患者(13/31,41.9%)和11例内分泌组患者(11/30,36.7%)可达到病理完全缓解(P>0.05),其临床完全缓解率分别为54.8%和50.0%,总体临床客观缓解率可达到93.5%和96.7%。值得注意的是,内分泌组的患者无4级不良反应,部分患者有腹泻或中性粒细胞减少等3级不良反应;化疗组约32.3%的病例发生以白细胞减少或中性粒细胞减少为主的4级不良反应,并且恶心、呕吐、疲乏、脱发等其余不良反应发生率明显增高。Cox回归模型提示:淋巴结转移和肿瘤大小是影响乳腺癌患者生存的不利因素。结论:乳腺癌靶向联合化疗与联合内分泌治疗的应用价值相似,但联合内分泌治疗在不良反应方面明显较轻,患者生活质量更高,因此该方案有望成为治疗HR阳性、HER-2阳性乳腺癌的新趋势,可在临床上广泛推广。

Objective:To explore the treatment efficacy and safety of two different neoadjuvant regimens for HR positive and HER-2 positive breast cancer.Methods:A randomized controlled method was conducted to enroll patients with over 60 years or under 60 years with menopause.All cases were pathologically confirmed with HER-2 positive(3+or Fish gene amplification),or HR positive stageⅡ-Ⅲoperable patients with tumor size>2 cm.We randomly assigned subjects with a 1∶1 ratio to receive two different neoadjuvant treatments and divided as follows:Patients in the chemotherapy group received trastuzumab+pertuzumab+albumin paclitaxel+carboplatin,as well as patients in the endocrine group received trastuzumab+pertuzumab+fulvestrant+palbociclib.Additionally,they would perform breast cancer surgery within 4 weeks after the completion of neoadjuvant therapy.Then we used a systematic random method to divide the two groups according to their T stages,lymph node numbers,and patient's age to compare the postoperative pathological complete remission rate(ypT_(0/is),ypN_(0)).Results:13 patients of chemotherapy group(13/31,41.9%)and 11 patients of endocrine group(11/30,36.7%)achieved pathological complete remission(P>0.05),and their clinical complete remission rates were 54.8%and 50.0%,as well as their overall clinical remission rate can reach 93.5%and 96.7%,respectively.It is worth noting that patients in the endocrine group had no grade 4 adverse events,only some patients had grade 3 adverse events such as diarrhea or neutropenia.Approximately 32.3%of chemotherapy cases occurred with leukopenia or neutropenia as the major grade 4 adverse events,and other adverse events such as nausea,vomiting,fatigue,and hair loss was significantly increased in this group.The Cox regression model suggests that lymph node metastasis and the size of the mass were unfavorable factors affecting the survival of breast cancer patients.Conclusion:The clinical application of targeted breast cancer combined chemotherapy or targeted therapy combined endocrine is similar,but therapy combined endocrine group has less side effects and higher life quality for patients.Therefore,this regimen is expected to be as a new treatment trend for HR positive,HER-2 patients,which would be widely promoted in clinical settings.