不同亚型乳腺癌脑转移患者的临床特征和生存分析

Clinical features and survival analysis of different subtypes of patients with breast cancer brain metastases

背景与目的:脑是乳腺癌常见转移部位之一,乳腺癌脑转移发生率在10%～15%,伴脑转移的乳腺癌患者预后较差。本研究目的在于分析4种不同亚型乳腺癌脑转移患者的临床特征及预后因素。方法:回顾分析1997年10月至2008年7月中山大学肿瘤防治中心收治的89例脑转移患者的资料,包括导管A型30例,导管B型20例,HER-2型16例,三阴型14例,另9例免疫组化结果不详。分析4种乳腺癌脑转移患者初诊时的临床病理特征、复发特点、影响复发后患者预后的因素等,并进一步对导管型乳腺癌患者的内分泌治疗进行研究。结果:全组患者中位年龄46岁(28～74岁),出现脑转移的时间与初诊时的病理分期密切相关,Ⅰ期患者最长(P<0.001)。中位随访时间41.0个月(6.0～141.0个月),全组中位生存时间8.0个月(0～80.0个月),1年生存率32.0%,5年生存率4.0%。多因素分析显示,PS评分大于1分、多发转移灶、未进行全脑放疗联合化疗均是不良预后因素。与导管A型乳腺癌相比,HER-2型和三阴型乳腺癌脑转移具有发生时间早、一线治疗后进展快(8.0个月vs.11.0个月)、总生存期短(25.0个月vs.63.0个月)等特点,导管A型具有进展缓慢、预后好的倾向,他莫昔芬能改善导管A型和导管B型患者的生存(中位生存时间24.0个月vs.7.0个月,P=0.002)。结论:乳腺癌脑转移生存期较短,其中HER-2型和三阴型预后更差。治疗以全脑放疗联合化疗为主。导管型患者接受他莫昔芬治疗有生存获益。

Background and Objective：The brain is one of the most common metastatic sites of breast cancer. Brain metastases develop in 10%-15% of patients with breast cancer and are associated with poor prognosis. The purpose of this retrospective study was to analyze the clinical characteristics and survival of patients with brain metastases due to breast cancer of different subtypes and to identify the prognostic factors that affect clinical outcome. Method：A total of 89 patients with breast cancer brain metastases diagnosed between October 1997 and July 2008 at Sun Yat-sen University Cancer Center were included in this study. Among the 89 patients,the number of luminal A,luminal B,human epidermal growth factor receptor 2 （HER-2）,and triple-negative （TN） subtypes were 30,20,16,and 14,respectively; 9 patients had an unknown subtype. The clinical characteristics,pathologic features,and prognostic factors were analyzed both at the initial diagnosis and at the diagnosis of brain metastases. Endocrine therapy for patients with luminal subtypes was further studied. Result：The median age of patients was 46 years （range 28-74 years）. The median survival time was 8.0 months （range 0-80 months）,the 1-year survival rate was 32% and the 5-year survival rate was 4%. The time to brain metastasis differed according to clinical stage at initial diagnosis,and the time for patients with the luminal A subtype was the longest （ P〈0.001）. Multivariate analysis demonstrated that performance status score1,multiple brain metastases and without whole brain radiotherapy （WBRT） in combination with chemotherapy were associated with poor prognosis. Compared with the luminal A subtype,features of the HER-2 and TN subtypes included early metastases,rapid progression after first-line treatment （8.0 months vs. 11.0 months）,and poor overall survival （25.0 months vs. 63.0 months）. The luminal A subtype showed a tendency for good prognosis and slow growth. Tamoxifen could improve the survival of luminal A/B subtypes （median survival 24.0 months vs. 7.0 months,respectively,P=0.002）. Conclusions：The prognosis of brain metastases from breast cancer was poor,especially in patients with HER-2 and TN subtypes. Generally,WBRT in combination with chemotherapy was the standard treatment modality. Patients with the luminal subtypes could benefit from tamoxifen.