【作者】 王萍；

【导师】 张研；

【作者基本信息】 吉林大学 ， 临床医学硕士（专业学位）， 2024， 硕士

【摘要】 背景:乳腺癌是一种常见的恶性肿瘤,已成为危害世界人口健康,尤其是女性健康的重大疾病之一^[1]。2024年国际癌症研究机构（International Agency for Research on Cancer,IARC）最新的流行病数据显示,乳腺癌的发病率位居全球第二,仅次于肺癌,并以67万死亡例数超越胃癌成为全球第四大癌症杀手,远超子宫癌和卵巢癌等妇科肿瘤^[2]。由此可见,乳腺癌的防治工作已刻不容缓。化疗是乳腺癌临床治疗的经典手段之一,可有效降低患者的复发风险,提高生存率。蒽环类药物是乳腺癌化疗的基石药物,临床上常用的有阿霉素/多柔比星（Adriamycin,ADM）和表阿霉素/表柔比星（Epirubicin,EPI）。尽管蒽环类药物对乳腺癌有显著疗效,但可能会产生心室功能障碍、心力衰竭和心律失常等危及生命的副作用,因此对其在临床中的应用产生了一定的限制。聚乙二醇多柔比星脂质体（Pegylated liposomal doxorubicin,PLD）是一种将盐酸多柔比星包封在脂质体内的新剂型,已被证实在转移性乳腺癌中的疗效与EPI相当,但毒性更低。目前PLD作为早期乳腺癌患者新辅助或辅助化疗的有效性和安全性还缺乏大样本数据支持,需要进一步研究。目的:回顾性分析于我院就诊并符合纳入条件的乳腺癌患者,比较PLD与EPI在乳腺癌新辅助及辅助化疗中的有效性及安全性。通过真实世界的对比研究,以期为乳腺癌患者在化疗药物的选择上提供更有价值的参考信息。方法:本研究收集了2021年10月至2023年6月就诊于吉大二院乳腺外科的乳腺癌患者,使用纳入及排除标准筛选后,将满足条件的患者分为PLD组和EPI组,并进行后续分析。首先,记录并分析患者的一般资料,包括患者年龄、绝经状态、联系方式、肿瘤TNM分期、术前穿刺及术后病理及免疫组化结果（ER、PR、HER-2、Ki-67）、分子分型、化疗方案及化疗周期等。采用SPSS 25.0软件进行统计学分析,计量资料满足正态分布采用均数±标准差表示,组间比较采用独立样本t检验;计数资料采用构成比或率表示,比较采用Pearson’s卡方检验或Fisher确切概率法;等级资料的比较采用秩和检验。p<0.05为差异有统计学意义。评估两组患者治疗的疗效以及安全性的差异。本研究的主要研究终点为病理完全缓解率（pathological complete response,p CR）和不良反应发生率;次要研究终点为总生存率（overall survival,OS）和无病生存率（disease-free survival,DFS）。结果:1.该研究共纳入265例患者,PLD组与EPI组在年龄、绝经状态、临床分期、病理类型、分子分型、Ki-67表达及化疗时机方面的差异均无统计学意义（p>0.05）,基线资料具有可比性。2.新辅助化疗后,PLD组和EPI组的p CR率分别为37.5%和32.4%,PLD组较EPI组稍高但无统计学差异（p=0.759）。各亚组中PLD组与EPI组的p CR率均未见明显差异（p>0.05）。3.PLD组和EPI两组间新辅助化疗后的DFS无显著性差异（97.6%vs97.1%,p=0.868）,且在随访过程中,OS均为100%,两组保持一致。4.对辅助化疗后的PLD组和EPI组患者进行生存分析,两组间的DFS（97.8%vs 97.9%,p=0.974）及OS均无显著性差异（100.0%vs 99.0%,p=0.335）。5.新辅助化疗患者中PLD组心电图异常的发生率低于EPI组,而手足综合征的发生率高于EPI组,差异均具有统计学意义。其余不良反应未见明显差异。6.辅助化疗患者中PLD组白细胞减少、恶心呕吐、脱发、心电图异常的发生率均低于EPI组,而手足综合征的发生率高于EPI组,差异均具有统计学意义。结论:1.PLD组新辅助化疗后的p CR率与EPI组相当。2.PLD组与EPI组新辅助或辅助化疗后的2年DFS与OS相当。3.在不良反应方面,PLD组心电图异常的发生率低于EPI组,安全性较好,可能更适用于既往有心脏病史的患者,PLD组手足综合征的发生率高于EPI组,虽然该不良反应可控,但仍需引起重视。更多还原

【Abstract】 Background:Breast cancer is a common malignant tumor,which has become one of the major diseases that significantly affect the health of the global population,particularly women’s health.According to the latest epidemiological data from the International Agency for Research on Cancer(IARC)in 2024,the incidence of breast cancer ranks second globally,second only to lung cancer,with 670,000 deaths,surpassing gastric cancer to become the fourth-largest cancer killer worldwide,far exceeding gynecological tumors such as uterine cancer and ovarian cancer.Therefore,the prevention and control of breast cancer are urgent.Chemotherapy is one of the classic methods for the clinical treatment of breast cancer,which can effectively reduce the risk of recurrence and improve survival rates.Anthracycline drugs,including doxorubicin/adriamycin(ADM)and epirubicin(EPI),are cornerstone drugs for breast cancer chemotherapy.Although anthracycline drugs have shown significant efficacy against breast cancer,they may cause life-threatening side effects such as ventricular dysfunction,heart failure,and arrhythmia,leading to certain limitations on their clinical application.Pegylated liposomal doxorubicin(PLD),a new formulation encapsulating doxorubicin hydrochloride in liposomes,has been proven to have efficacy comparable to EPI in metastatic breast cancer but with lower toxicity.However,the effectiveness and safety of PLD as neoadjuvant or adjuvant chemotherapy for early-stage breast cancer patients currently lack large-sample data support and require further research.Objective:A retrospective analysis was conducted on breast cancer patients who were treated at our hospital and met the inclusion criteria,comparing the effectiveness and safety of PLD and EPI in neoadjuvant and adjuvant chemotherapy for breast cancer.Through real-world comparative studies,we aim to provide more valuable reference information to assist breast cancer patients in selecting chemotherapy drugs.Methods:This study collected breast cancer patients treated at the Second Hospital of Jilin University from October 2021 to June 2023.After screening using inclusion and exclusion criteria,eligible patients were divided into the PLD group and the EPI group for subsequent analysis.Firstly,the general information of patients was recorded and analyzed,including patient age,menopausal status,contact information,tumor TNM staging,preoperative puncture,postoperative pathological and immunohistochemical results(ER,PR,HER-2,Ki-67),molecular subtypes,chemotherapy regimens,and chemotherapy cycles.Statistical analysis was performed using SPSS 25.0 software.Normally distributed measurement data were expressed as mean ± standard deviation,and independent sample t-tests were used for intergroup comparisons.Count data were expressed as composition ratios or rates,and comparisons were made using Pearson’s chi-square test or Fisher’s exact probability method.Rank data comparison was conducted using rank-sum tests.A P value < 0.05 was considered statistically significant.The study evaluated the differences in treatment efficacy and safety between the two patient groups.The primary endpoint of this research was the rate of pathological complete response(p CR)and the incidence of adverse reactions;secondary endpoints included overall survival(OS)and diseasefree survival(DFS)rates.Results:1.This study enrolled a total of 265 patients.There were no statistically significant differences between the PLD group and the EPI group in terms of age,menopausal status,clinical stage,pathological type,molecular subtype,Ki-67 expression,and timing of chemotherapy(P > 0.05).The baseline data showed comparability.2.Following neoadjuvant chemotherapy,the pathological complete response(p CR)rates in the PLD group and the EPI group were 37.5% and 32.4%,respectively.Although the PLD group exhibited a slightly higher p CR rate compared to the EPI group,this disparity lacked statistical significance(P = 0.759).Moreover,there were no significant differences in p CR rates between the PLD and EPI groups across various subgroups(P > 0.05).3.Post-neoadjuvant chemotherapy,there was no significant discrepancy in diseasefree survival(DFS)between the PLD group and the EPI group(97.6% vs.97.1%,P =0.868).Additionally,throughout the follow-up period,overall survival(OS)remained consistent at 100% in both groups.4.Survival analysis of patients receiving adjuvant chemotherapy in both the PLD and EPI groups revealed no significant differences in DFS(97.8% vs.97.9%,P = 0.974)and OS(100.0% vs.99.0%,P = 0.335)between the two cohorts.5.Among patients undergoing neoadjuvant chemotherapy,the PLD group exhibited a lower incidence of abnormal electrocardiograms compared to the EPI group,while the incidence of hand-foot syndrome was higher in the PLD group,with both discrepancies being statistically significant.No notable differences were observed in other adverse reactions.6.In patients undergoing adjuvant chemotherapy,the PLD group demonstrated lower incidences of leukopenia,nausea and vomiting,alopecia,and abnormal electrocardiograms compared to the EPI group,while the incidence of hand-foot syndrome was higher in the PLD group,with all differences being statistically significant.Conclusions:1.The pathological complete response(p CR)rate after neoadjuvant chemotherapy in the PLD group is comparable to that in the EPI group.2.The 2-year disease-free survival(DFS)and overall survival(OS)rates after neoadjuvant or adjuvant chemotherapy are similar between the PLD group and the EPI group.3.Regarding adverse reactions,the incidence of abnormal electrocardiograms in the PLD group is lower than that in the EPI group,indicating better safety.PLD may be more suitable for patients with a history of heart disease.However,the incidence of hand-foot syndrome is higher in the PLD group compared to the EPI group.Although this adverse reaction is controllable,it still requires attention.更多还原