Her-2阳性乳腺癌患者曲妥珠单抗联合新辅助化疗的效果评价及其预后影响因素分析

doi:10.13481/j.1671-587x.20160230

摘要/Abstract

摘要：

目的: 评价曲妥珠单抗联合新辅助化疗用于人类表皮生长因子受体2(Her-2)阳性乳腺癌患者的疗效,探讨乳腺癌患者的预后影响因素。方法: 回顾性分析112例Her-2阳性乳腺癌患者的临床资料,根据是否应用曲妥珠单抗治疗分为靶向联合化疗组和单纯化疗组。采用SPSS19.0软件对患者的临床特征进行统计分析,采用Kaplan-Meier法进行生存分析,应用Log-rank检验绘制生存曲线,采用Cox回归分析进行单因素及多因素预后分析。结果: 112例Her-2阳性乳腺癌患者中,靶向联合化疗组23例(20.54%),单纯化疗组89例(79.46%)。靶向联合化疗组患者的无病生存期(DFS)显著长于单纯化疗组(P=0.012),靶向联合化疗组患者总生存期(OS)虽然长于单纯化疗组,但组间比较差异无统计学意义(P=0.064)。激素受体(HR)阴性组Miller Payne(MP)分级为5级的患者18例(32.7%),多于HR阳性组的5例(10.9%)(P=0.009)。Cox回归单因素分析,原发肿物大小、初诊时区域淋巴结情况及术后淋巴结情况是Her-2阳性患者DFS的影响因素;原发肿物大小、初诊时区域淋巴结情况、MP分级及术后淋巴结情况是Her-2阳性乳腺癌患者OS的影响因素。多因素分析,原发肿物大小、初诊时区域淋巴结情况、是否接受放疗是Her-2阳性乳腺癌患者DFS及OS的独立影响因素。结论: HR阴性的Her-2阳性乳腺癌患者接受曲妥珠单抗联合新辅助化疗后乳房病灶可获得显著缓解。曲妥珠单抗联合新辅助化疗治疗Her-2阳性乳腺癌患者可以显著提高患者的DFS,对患者的预后具有积极的影响。

关键词: 乳腺肿瘤, 人类表皮生长因子受体2, 曲妥珠单抗, 预后

Abstract:

Objective: To assess the efficacy of trastuzumab combined with neoadjuvant chemotherapy in the treatment of human epidermal growth factor receptor-2 (Her-2) positive breast cancer patients, and to explore its influencing factors of prognosisof breast cancer.Methods: The clinical materials of 112 Her-2 positive breast cancer patients were collected and they were divided into combined treatment group (trastuzumab+neoadjuvant chemotherapy) and single chemotherapy group (without trastuzumab).SPSS 19.0 software was employed to calculate and analyze their clinical characteristics.The survival rate and prognosis were analyzed by Kaplan-Meier method, Log-rank test, and Cox regression.Results: Among the 112 Her-2 positive breast cancer patients, 23 cases were treated with trastuzumab, 89 cases were treated without trastuzumab.The disease-free survival (DFS) in combined treatment group and single chemotherapy group had significant difference (P=0.012).And there was no significant difference of overall survival (OS) between two groups (P=0.064).The HR negative group had 18(32.7%) patients with 5-level of Miller and Payne (MP) classification which was higher than HR positive group(5/46, 10.9%) (P=0.009).In univariate analysis, the tumor size, node status at diagnosis and node status after operation were the influencing factors of DFS in the Her-2 positive breast cancer patients; the tumor size, node status at diagnosis, MP classification and node status after operation were the influencing factors of OS in the Her-2 positive breast cancer patients.The result of multivariate analysis indicated that the tumor size, node status at diagnosis, and with or without radiotherapy were the independent influencing factors of DFS and OS in the Her-2 positive breast cancer patients.Conclusion: The breast lesions in the Her-2 positive breast cancer patients with negative HR are relieved after treated with trastuzumab combined with neoadjuvant chemotherapy.The combination of trastuzumab and neoadjuvant chemotherapy can significantly improve the DFS and has a positive influence in the prognosis of Her-2 positive breast cancer patients.

Key words: breast neoplasms, human epidermal growth factor receptor 2, trastuzumab, prognosis

中图分类号:

R737.9

邵婉婷, 付彤, 武盼盼, 吴迪, 李嗣杰, 郑超, 范志民. Her-2阳性乳腺癌患者曲妥珠单抗联合新辅助化疗的效果评价及其预后影响因素分析[J]. 吉林大学学报(医学版), 2016, 42(02): 351-357.

SHAO Wanting, FU Tong, WU Panpan, WU Di, LI Sijie, ZHENG Chao, FAN Zhimin. Evaluation on efficacy of trastuzumab combined with neoadjuvant chemotherapy in Her-2 positive breast cancer patients and analysis of influencing factors of prognosis[J]. Journal of Jilin University Medicine Edition, 2016, 42(02): 351-357.

参考文献

[1] Slamon DJ,Godolphin WA,Jones LA,et al.Studies of the HER-2/neu proto-oncogene in human breast and ovarian cancer[J].Science,1989,244(4905):707-712.

[2] Perez EA,Romond EH,Suman VJ,et al.Trastuzumab Plus adjuvant chemotherapy for human epidermal growth factor receptor 2-positive breast cancer:planned joint analysis of overall survival from NSABP B-31 and NCCTG N9831[J].J Clin Oncol,2014,32(33):3744-3752.

[3] Slamon DJ,Leyland-Jones B,Shak S,et al.Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2[J].N Engl J Med,2001,344(11):783-792.

[4] van der Hage JA,van de Velde CJH,Julien JP,et al.Preoperative chemotherapy in primary operable breast cancer:Results from the European Organization for Research and Treatment of Cancer trial 10902[J].J Clin Oncol,2001,19(22):4224-4237.

[5] Valachis A,Mauri D,Polyzos NP,et al.Trastuzumab combined to neoadjuvant chemotherapy in patients with HER2-positive breast cancer:A systematic review and meta-analysis[J].Breast,2011,20(6):485-490.

[6] Demonty G,Bernard-Marty C,Puglisi F,et al.Progress and new standards of care in the management of HER-2 positive breast cancer[J].Eur J Cancer,2007,43(3):497-509.

[7] Buzdar AU,Ibrahim NK,Francis D,et al.Significantly higher pathologic complete remission rate after neoadjuvant therapy with trastuzumab,paclitaxel,and epirubicin chemotherapy:Results of a randomized trial in human epidermal growth factor receptor 2-positive operable breast cancer[J].J Clin Oncol,2005,23(16):3676-3685.

[8] Chia SK.Neoadjuvant and adjuvant therapy for her2 positive disease[J].Am Soc Clin Oncol Educ Book,2015,35:e41-e48.

[9] Buzdar AU,Valero V,Ibrahim NK,et al.Neoadjuvant therapy with paclitaxel followed by 5-fluorouracil,epirubicin,and cyclophosphamide chemotherapy and concurrent trastuzumab in human epidermal growth factor receptor 2-positive operable breast cancer:An update of the initial randomized study population and data of additional patients treated with the same regimen[J].Clin Cancer Res,2007,13(1):228-233.

[10] Gianni L,Eiermann W,Semiglazov V,et al.Neoadjuvant chemotherapy with trastuzumab followed by adjuvant trastuzumab versus neoadjuvant chemotherapy alone,in patients with HER2-positive locally advanced breast cancer (the NOAH trial):a randomised controlled superiority trial with a parallel HER2-negative cohort[J].Lancet,2010,375(9712):377-384.

[11] Gianni L,Eiermann W,Semiglazov V,et al.Follow-up results of NOAH,a randomized phase Ⅲ trial evaluating neoadjuvant chemotherapy with trastuzumab (CT plus H) followed by adjuvant H versus CT alone,in patients with HER2-positive locally advanced breast cancer[J].J Clin Oncol,2013,31(15):503.

[12] Peintinger F,Buzdar AU,Kuerer HM,et al.Hormone receptor status and pathologic response of HER2-positive breast cancer treated with neoadjuvant chemotherapy and trastuzumab[J].Ann Oncol,2008,19(12):2020-2025.

[13] Limentani SA,Brufsky AM,Erban JK,et al.Phase Ⅱ study of neoadjuvant docetaxel,vinorelbine,and trastuzumab followed by surgery and adjuvant doxorubicin plus cyclophosphamide in women with human epidermal growth factor receptor 2-overexpressing locally advanced breast cancer[J].J Clin Oncol,2007,25(10):1232-1238.

[14] Guarneri V,Broglio K,Kau SW,et al.Prognostic value of pathologic complete response after primary chemotherapy in relation to hormone receptor status and other factors[J].J Clin Oncol,2006,24(7):1037-1044.

[15] Gianni L,Eiermann W,Semiglazov V,et al.Neoadjuvant and adjuvant trastuzumab in patients with HER2-positive locally advanced breast cancer (NOAH):follow-up of a randomised controlled superiority trial with a parallel HER2-negative cohort[J].Lancet Oncol,2014,15(6):640-647.

[16] Ogston KN,Miller ID,Payne S,et al.A new histological grading system to assess response of breast cancers to primary chemotherapy:prognostic significance and survival[J].Breast,2003,12(5):320-327.

[17] Chang HR.Trastuzumab-based neoadjuvant therapy in patients with her2-positive breast cancer[J].Cancer,2010,116(12):2856-2867.

[18] 廖宁,张国淳,李学瑞,等.新辅助紫杉醇联合曲妥珠单抗在表皮生长因子受体2阳性可手术乳腺癌患者中的疗效及安全性评价[J].中华肿瘤杂志,2010,32(7):544-547.

[19] 姚恒,赵玲,李索妮,等.紫杉醇脂质体对乳胶癌细胞SK-BR-3的放疗增敏作用及其机制[J].西安交通大学学报:医学版,2015,36(5):628-633.

[20] 曹志宇,何建苗,杨波,等.局部晚期乳腺癌新辅助化疗联合保乳手术的临床疗效观察:附81例报告[J].解放军医学杂志,2015,40(6):488-491.