不同分子亚型乳腺癌首发肝转移患者的临床特征和预后

Clinical features and prognosis of patients with first-episode liver metastasis of different molecular subtypes of breast cancer

目的 分析不同分子亚型乳腺癌肝转移患者的临床特征和预后,探讨乳腺癌肝转移预后相关的危险因素.方法 收集2009年1月至2014年1月于四川大学华西医院住院的122例乳腺癌首发肝转移患者的临床资料.根据乳腺癌外显型细胞表面受体进行分型,包括Luminal A型、Luminal B型、人表皮生长因子（HER2）过表达型和三阴性型（TNBC）共4个分子亚型.分析患者初诊时的年龄、人体质量指数、月经状态、cTNM分期、复发时乳酸脱氢酶和碱性磷酸酶水平、肝转移情况、治疗情况等与预后的相关性.计数资料采用χ2检验及Fisher精确概率法,生存分析采用Kaplan-Meier法,影响因素的单因素分析采用Log rank检验,多因素分析采用Cox风险回归模型.结果 122例患者中,Luminal A型12例,Luminal B型61例,HER2过表达型30例,TNBC型19例.Luminal A型、Luminal B型、HER2过表达型和TNBC型中位无疾病生存期（DFS）分别为32、23、16和10个月（P=0.001）;中位总生存期（OS）分别为54、35、26和13个月（P=0.003）.肝转移后中位OS分别为30、16、10和9个月（P=0.019）,差异均有统计学意义.HER2阳性的患者中,既往用曲妥珠单克隆抗体可明显延长患者的生存时间,分别延长11个月（DFS）和18个月（OS）（P＜0.05）.多因素分析结果显示,cTNM分期、分子亚型和靶向治疗是影响乳腺癌肝转移患者DFS的独立影响因素（P＜0.05）.人体质量指数、复发时乳酸脱氢酶升高、cTNM分期、分子亚型、解救化学治疗、放射和靶向治疗是影响乳腺癌肝转移患者OS的独立影响因素（P＜0.05）.TNBC型、HER2过表达型和Luminal B型患者的预后比Luminal A型差,这3类患者的复发风险分别是Luminal A型的15.97、8.81和4.76倍;死亡风险分别是Luminal A型的8.42、6.02和3.86倍.结论 乳腺癌首发肝转移患者的预后与肝转移发生时乳酸脱氢酶增高程度、人体质量指数、cTNM分期和分子分型有关.与Luminal型患者比较,HER2过表达型和TNBC型患者易于早期出现肝转移,且OS较短.解救化学治疗、靶向治疗和放射治疗可以明显改善肝转移患者的预后.

Objective To investigate the clinical features and prognosis of patients with first-episode liver metastasis of different molecular subtypes of breast cancer and risk factors for liver metastasis of breast cancer.Methods A retrospective analysis was performed for 122 breast cancer patients with first-episode liver metastasis from January 2009 to January 2014.According to the cell surface receptors of breast cancer,these patients were divided into the four molecular subtypes of Luminal A,Luminal B,human epidermal growth factor receptor 2 （HER2） overexpression,and triple-negative breast cancer （TNBC）.The association of patients＇ age at initial diagnosis,body mass index （BMI）,menstruation status,clinical TNM （cTNM） stage,levels of lactate dehydrogenase （LDH） and alkaline phosphatase （ALP） at recurrence,liver metastasis,and treatment condition with the patients＇ prognosis were analyzed.The chi-square test and Fisher＇s exact test were used for categorical data,the Kaplan-Meier method was used for survival analysis,the log-rank test was used for univariate analysis of influencing factors,and the Cox regression model was used for multivariate analysis.Results Among the 122 patients,12 had Luminal A subtype,61 had Luminal B subtype,30 had HER2 overexpression subtype,and 19 had TNBC subtype.In the patients with Luminal A,Luminal B,HER2 overexpression,and TNBC subtypes,the median disease-free survival （DFS） was 32,23,16,and 10 months,respectively （P =0.001）,the median overall survival （OS） was 54,35,26,and 13 months,respectively （P =0.003）,and the median OS after liver metastasis was 30,16,10,and 9 months,respectively （P =0.019）.In HER2-positive patients,the application of trastuzumab in the past significantly prolonged the patients＇ DFS by 11 months and OS by 18 months （P ＜ 0.05）.The results of the multivariate analysis showed that cTNM stage,molecular subtype,and targeted therapy were independent influencing factors for DFS of breast cancer patients with liver metastasis （P ＜ 0.05）,and that BMI,increased LDH at recurrence,cTNM stage,molecular subtype,salvage chemotherapy,radiotherapy,and targeted therapy were independent influencing factors for OS of breast cancer patients with liver metastasis （P ＜ 0.05）.The patients with TNBC,HER2 overexpression,and Luminal B subtypes exhibited worse prognosis and had a risk of recurrence 15.97,8.81,and 4.76 times higher than those with Luminal A subtype.The risk of death in the patients with TNBC,HER2 overexpression,and Luminal B subtypes was 8.42,6.02,and 3.86 times that in those with Luminal A subtype.Conclusion The prognosis of breast cancer patients with first-episode liver metastasis is associated with the increase in LDH when liver metastasis occurs,BMI,cTNM stage,and molecular subtype.Compared with the patients with Luminal subtypes,those with HER2 overexpression and TNBC subtypes tend to develop liver metastasis in early stage and have a shorter OS.Salvage chemotherapy,targeted therapy,and radiotherapy can significantly improve the prognosis of patients with liver metastasis.